Evolution of flu strains points to higher risk (H7 and H9)

authorwktdtime11 Mar 2010categoryportal.gzgq.com
  • Evolution of flu strains points to higher risk

    (AFP)

    26 May 2008

    CHICAGO - Some strains of bird flu are coming ever closer to developing the traits they need to cause a human pandemic, a study released Monday said.

    Researchers who analysed samples of recent avian flu viruses found that a few H7 strains of the virus that have caused minor, untransmissible infections in people in North America between 2002 and 2004 have increased their affinity for the sugars found on human tracheal cells.

    Subsequent tests in ferrets suggested that these viral strains were not readily transmissible.

    But one strain of the H7N2 virus, a low pathogenic avian flu strain isolated from a man in New York in 2003, replicated in the ferret's respiratory tract and was passed between infected and uninfected ferrets suggesting it could be transmissible in humans.

    The investigators said the evidence suggests that the virus could be evolving toward the same strong sugar-binding properties of the three worldwide viral pandemics in 1918, 1957 and 1968.

    "These findings suggest that the H7 class of viruses are partially adapted to recognize the receptors that are preferred by the human influenza virus," said Terrence Tumpey, a senior microbiologist with the US Centers for Disease Control and Prevention in Atlanta.

    The authors said that if the viruses continue to evolve in this direction, the avian flu viruses could travel more easily between other animals and humans. They called for strict surveillance of avian flu viruses and continuing federal preparations for a possible future pandemic.

    The study appears in the Proceedings of the National Academy of Sciences.


    http://www.khaleejtimes.com/DisplayArticleNew.asp?xfile=data/theworld/2008/May/theworld_May1165.xml§ion=theworld


  • CDC has pulled sequences

    http://www.flutrackers.com/forum/showpost.php?p=152098&postcount=1


    So, do we have the only publicly available set of these sequences?


  • Scientists warn of bird flu epidemic

    By Andy Bloxham
    Last updated: 7:00 AM BST 27/05/2008

    A strain of bird flu has moved a step closer to developing the traits required to create an epidemic of the disease in humans, scientists warned on Monday.



    Researchers who analysed samples of recent avian flu viruses found that a strain of the virus called H7N2 had adapted slightly better to living in mammals.
    Tests on ferrets proved the strain could be passed between animals but scientists said the evidence suggested that bird flu could be transmitted between humans.
    Dr Terrence Tumpey, a microbiologist with the US Centers for Disease Control and Prevention, in Atlanta, Georgia, said: "The finding underscores the necessity for continued surveillance and study of these viruses as they continue to resemble viruses with pandemic potential."
    The virus tested on the ferrets - a standard animal model of flu in humans - was isolated from a man in New York in 2003, where it thrived on the same sugars found in the human windpipe.
    The scientists said the virus could be evolving toward the same strong sugar-binding properties of the three worldwide viral pandemics in 1918, 1957 and 1968.
    Like H5N1, the H7 family of flu viruses also primarily affects birds.
    A deadly version of the H7N7 strain hit poultry in the Netherlands in 2003, and a less severe form, H7N2, broke out in the UK last year.
    Some have estimated the death toll of an avian flu pandemic could be 100 million, including 500,000 in Britain.
    The World Bank estimates that the financial cost of a pandemic could exceed $2 trillion.
    The study appeared in the journal Proceedings of the National Academy of Sciences.


    Story from Telegraph News:
    http://www.telegraph.co.uk/news/worldnews/northamerica/usa/2035638/Scientists-warn-of-bird-flu-epidemic.html


  • AVIAN INFLUENZA H7 - NORTH AMERICA: HUMAN RECEPTOR
    **************************************************
    A ProMED-mail post

    ProMED-mail is a program of the
    International Society for Infectious Diseases


    ******
    [1]
    Date: Mon 26 May 2008
    Source: Bloomberg.com [edited]



    Mild American Bird-Flu Strains Gained Ability to Attack Humans
    --------------------------------------------------------------
    Mild bird flu strains circulating in North
    America have gained some ability to infect human
    cells, and should be monitored for dangerous
    mutations, government researchers said. The virus
    family [i.e., the influenza virus serotype -
    Mod.CP], called H7, is genetically different than
    the H5N1 strain that has killed millions of birds
    and hundreds of people, said Terrence Tumpey, a
    U.S. Centers for Disease Control and Prevention
    (CDC) scientist in Atlanta. More mutations in the
    H7 strain could make it dangerous to humans, he
    said. People don't have natural immunity [i.e.,
    innate resistance] to many strains of flu
    spreading in birds, allowing these viruses to
    cause severe infections when they enter human
    cells. Some strains of H7 have increased their
    ability to stick to proteins on the surface of
    human lung cells, a key step in infection that
    may at some point allow its spread from one human
    to another, Tumpey said in a study in the
    Proceedings of the National Academy of Sciences
    journal. "This underscores the importance of
    continued surveillance so we can be best prepared
    for early response to a pandemic threat," he said
    in a telephone interview.

    At least 241 people have died of H5N1 bird flu
    since 2003, most of them in Asia. A worldwide
    network of laboratories collects and analyzes
    samples for mutations that might allow the virus
    to spread quickly from person to person. Tumpey
    analyzed H7 viruses that infected poultry and
    people from 2002 through 2004. One was an H7
    strain that caused an outbreak in the Netherlands
    in 2003, infecting about 80 people and killing
    one person. That strain wasn't well adapted to
    human lung cells, and most human infections were
    in the eye, Tumpey said. His analysis showed the
    virus prefers attaching to a molecule in birds'
    intestines, called alpha 2-3[-linked sialic
    acid]. Other H7 strains circulating at the same
    time in Canada and the U.S., however, had the
    ability to attach to a cell surface molecule
    called alpha 2-6[-linked sialic acid]. That
    molecule is found in the breathing tissues of
    humans and animals, and is a common target for
    seasonal flu viruses that cause annual outbreaks
    and spread quickly through the population, he
    said.

    One H7 strain that infected a New York man in
    2004 was easily transmitted among ferrets, the
    study showed. Ferrets and humans are susceptible
    to many of the same flu viruses. While the
    finding is important, other characteristics
    probably contribute to the ability of viruses to
    spread and make people ill, said Albert
    Osterhaus, a virologist at the Erasmus Medical
    Center in Rotterdam. Other factors, such as
    whether the virus grows in the human nose and
    throat, rather than deep in the lungs, may allow
    it to spread quickly, he said. "Those that
    replicate in the upper respiratory tract are more
    likely to be transmitted between mammals," he
    said in a telephone interview. The ability to
    bind to human cells "is not the whole story."

    While these H7 viruses are "low pathogenic,"
    meaning they rarely cause deaths [in birds], they
    nonetheless pose a threat, Tumpey said. "We have
    to be aware of these viruses just like we're
    aware of H5 viruses," he said. "They have the
    potential to mutate to high pathogenic and they
    are in our backyard."

    A total of 3 influenza pandemics occurred last
    century in 1918, 1957 and 1968. The most lethal
    by far was the 1918 "Spanish flu" that killed as
    many as 50 million people worldwide.

    [Byline: John Lauerman]

    --
    Communicated by:
    ProMED-mail


    ******
    [2]
    Date: Mon 26 May 2008
    Source: The Times online [edited]



    Scientists identify 2nd H7 strain of bird flu that could cause pandemic
    -----------------------------------------------------------------------
    The H5N1 strain of bird flu that has killed 241
    people is not the only one that could trigger a
    pandemic, according to research in America. A few
    H7 strains of the flu virus have started to
    evolve some of the traits they would need to
    infect people easily, scientists have discovered.
    The findings, from a team led by Terrence Tumpey,
    of the US Centers for Disease Control and
    Prevention (CDC) in Atlanta, show that while
    there is no immediate indication that H7 flu is
    about to acquire potentially damaging mutations,
    it is critical that global surveillance and
    research covers this virus class [i.e., influenza
    virus


  • accessionlengthhostsegmentsubtypecountryyearVirus name23 nucleotide sequencesAgeGender
    DQ9974182341Swine1 (PB2)H9N2China2003Influenza A virus (A/swine/Shandong/na/2003(H9N2))
    DQ9974272300Swine1 (PB2)H9N2China2003Influenza A virus (A/swine/Shandong/nb/2003(H9N2))
    EU5163092341Swine1 (PB2)H9N2China2003Influenza A virus (A/swine/Shandong/w4/2003(H9N2))
    DQ981599822Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fHZ/2003(H9N2))
    DQ9815752099Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fJN/2003(H9N2))
    DQ9816151002Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fLS/2003(H9N2))
    DQ9816072207Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fNY/2003(H9N2))
    DQ9816231115Swine1 (PB2)H9N2China2003Influenza A virus(A/swine/Shandong/fZC/2003(H9N2))
    EU5163172341Swine1 (PB2)H9N2China2004Influenza A virus (A/swine/Guangdong/wxl/2004(H9N2))
    EU5028982341Swine1 (PB2)H9N2China2004Influenza A virus (A/swine/Jiangxi/1/2004(H9N2))
    EU5029062341Swine1 (PB2)H9N2China2004Influenza A virus (A/swine/Jiangxi/wx2/2004(H9N2))
    DQ981583846Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/2/2004(H9N2))
    DQ9815352040Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/3/2004(H9N2))
    DQ981543831Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/4/2004(H9N2))
    DQ9815592034Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/5/2004(H9N2))
    DQ981591848Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/6/2004(H9N2))
    DQ981551860Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/7/2004(H9N2))
    DQ9815672084Swine1 (PB2)H9N2China2004Influenza A virus(A/swine/Henan/8/2004(H9N2))
    EF6127492341Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Guangxi/58/2005(H9N2))
    EU0863162341Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Guangxi/FS2/2005(H9N2))
    EU0863322341Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Guangxi/S11/2005(H9N2))
    EU0863332341Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Guangxi/S15/2005(H9N2))
    DQ9974351164Swine1 (PB2)H9N2China2005Influenza A virus (A/swine/Shandong/nc/2005(H9N2))




    differences in the 8 segments in 0/00


    A/swine/Shandong/fNY/2003(H9N2)
    A/swine/Shandong/2/03(H5N1)
    4, 18, 7,403, 5,467, 17, 0



    and in segment 2 (PB1) : {and Henan - segment 5}



    18 >A/swine/Guangxi/S11/2005(H9N2)
    19 >A/swine/Guangxi/58/2005(H9N2)
    20 >A/swine/Guangxi/S15/2005(H9N2)

    23 >A/swine/Guangxi/wz/2004(H5N1) 18: 69, 38, 94,394, 86,443, 71, 97, - 19: 62, 39, 94,395, 86,445, 66, 97, - 20:113, 37, 94,394, 84,445, 66, 99
    24 >A/swine/Henan/wy/2004(H5N1) 18: 64, 20, 94,395, 23,446, 90,100, - 19: 47, 20, 94,396, 23,447, 85,100, - 20:105, 20, 94,395, 21,447, 85,102
    25 >A/swine/Anhui/ca/2004(H5N1) 18: 67, 23, 96,398, 91,453, 92,102, - 19: 52, 23, 96,399, 90,455, 87,102, - 20:108, 23, 96,398, 88,455, 87,105
    26 >A/swine/Fujian/1/2003(H5N1) 18: 84, 23, 95,397, 68,444, 86, 96, - 19: 78, 23, 95,398, 68,445, 81, 96, - 20:120, 22, 94,397, 67,445, 81, 98
    27 >A/swine/Fujian/F1/2001(H5N1) 18: 83, 25, 96,393, 68,446, 83, 94, - 19: 78, 25, 96,395, 68,447, 78, 94, - 20:120, 24, 95,393, 67,447, 78, 97


  • Earlier discussion - Title of thread: Human H7N2 in New York

    http://www.flutrackers.com/forum/showthread.php?t=66348


  • I remember when Webster in mid 2006 at the height of the H5N1-concern
    said, that he currently examines H9N2, which might cause a pandemic too,
    is another hot candidate.

    This gave me some relief after he just had said : 50% likelyhood of a H5N1-pandemic
    and 50% of the world's population could die.

    Nothing special with H9N2, no WHO-alert-level, it has been around since long
    so the danger should be as it was the last centuries (or not ?)

    So Webster did put H5N1 in the same category a H9N2, also his semi-retraction
    and not repeating the 50% statement, which made me feel a little more easy in
    later 2006 than I had felt in early 2006 until the Karo cluster.

    Now, H7 has been documented in 1902 as "fowl plague" and reports back to 1870
    about fowl plague were probably also H7. No problems for humans ever.
    Why now ?

    I can see the changes with H5N1 since 1997, but what's new with H7 ?


  • And from Avian Flu Diary . . .

    Study: H7 Strains Evolving

    # 2019

    What little media attention we've seen surrounding pandemic flu over the past few years has been largely focused on the H5N1 bird flu virus. Scientists know, however, that there are other influenza's out there in the running to spark the next pandemic.

    The H7 virus, while a dark horse candidate, has already made a small number of campaign appearances.


    The following is a list of known of human H7 infections since 2002 (stats borrowed from CIDRAP's (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/) Summary of Avian Influenza Cases in Humans (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html))

    2002 H7N2 1 case United States (Virginia) Evidence of infection was found in one person in Virginia following a poultry outbreak

    2003 H7N7 89 cases (1 death) The Netherlands During an outbreak of H7N7 avian influenza in poultry, infection spread to poultry workers and their families in the area (see References (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html#_Influenza_Pandemics_of): Fouchier 2004, Koopmans 2004, Stegeman 2004). Most patients had conjunctivitis and several complained of influenza-like illness. The death occurred in a 57-year-old veterinarian. Subsequent serologic testing demonstrated that additional case-patients had asymptomatic infection.

    2003 H7N2 1 New York The source of exposure was not determined

    2004 H7N3 2 cases Canada (British Columbia) Two poultry workers became ill during an outbreak of H7N3 avian influenza in poultry (see References (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html#_Influenza_Pandemics_of): Health Canada 2004). Both had conjunctivitis.
    And 4 people were confirmed to have contracted H7N2 in the UK last year. . . . .

    http://afludiary.blogspot.com/2008/05/study-h7-strains-evolving.html


  • A H9 human vaccine is being developed, not without a good reason.

    11 studies with search of: H9 vaccine

    1 Completed Safety of and Immune Response to a Bird Flu Virus Vaccine (H9N2) in Healthy Adults (Study A)
    Conditions: Influenza; Virus Diseases
    Intervention: Biological: H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)

    2 Recruiting H9 Priming Study in Healthy Adults
    Condition: Influenza
    Intervention: Biological: Subvirion inactivated influenza A/H9N2 (G9 variant) vaccine

    3 Completed Safety of and Immune Response to a Bird Flu Virus Vaccine (H9N2) in Healthy Adults (Study B)
    Conditions: Influenza; Virus Diseases
    Intervention: Biological: H9N2 (6-2) AA ca Reassortant (A/Chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)

    4 Completed Inactivated Influenza A/H9N2 Vaccine With and Without MF59 Adjuvant in Ambulatory Adults
    Condition: Influenza
    Interventions: Biological: Influenza A/H9N2 vaccine; Drug: MF59 adjuvant

    5 Completed Safety Study of Pandemic Candidate Influenza Vaccines in the Elderly Population
    Condition: Influenza
    Intervention: Biological: 3 adjuvanted pandemic influenza candidate vaccines + 4 non-adjuvanted pandemic influenza candidate vaccines

    6 Active, not recruiting Study Evaluating 13-Valent Pneumococal Conjugate Vaccine in Healthy Infants
    Condition: Vaccines, Pneumococcal Conjugate Vaccine
    Interventions: Biological: 13-valent Pneumococcal Conjugate Vaccine; Biological: 7-valent pneumococcal conjugate vaccine

    7 Active, not recruiting Partially Blind Study to Evaluate Immunogenicity & Safety of GSK Bios' HPV Vaccine 580299 in Healthy Women Aged 9-25 Yrs
    Conditions: Papillomavirus Infections; Cervical Cancer
    Intervention: Biological: HPV vaccine 580299

    8 Recruiting Follow-up Study to Evaluate the Safety and Immunogenicity of a HPV Vaccine (580299) in North America
    Condition: Human Papillomavirus Infection
    Intervention: Biological: HPV (580299) vaccine

    9 Active, not recruiting Safety and Efficacy of HEPLISAV™ Hepatitis B Virus Vaccine Compared With Engerix-B® Vaccine
    Condition: Hepatitis B
    Interventions: Biological: 1018 ISS immunostimulatory oligonucleotide with HBV surface antigen; Biological: Hepatitis B Vaccine (Recombinant)

    10 Active, not recruiting GVAX® Vaccine for Prostate Cancer vs Docetaxel & Prednisone in Patients With Metastatic Hormone-Refractory Prostate Cancer
    Condition: Prostate Cancer
    Interventions: Biological: Immunotherapy with allogeneic prostate vaccine; Drug: Chemotherapy (Taxotere and prednisone)

    11 Recruiting Study to Evaluate the Safety and Effectiveness of Zostavax® in Subjects 50 - 59 Years of Age
    Condition: Shingles
    Interventions: Biological: Zoster Vaccine, Live, (Oka-Merck); Biological: Comparator: placebo (unspecified)

    http://clinicaltrials.gov/ct2/results?term=H9+vaccine



    H7 clinical trials :

    1 Completed Single Group Study of the Safety of and Immune Response to a Bird Flu Vaccine (H7N3) in Healthy Adults
    Conditions: Influenza; Virus Diseases
    Intervention: Biological: Live Influenza A Vaccine H7N3 (6-2) AA ca Recombinant (A/chicken/British Columbia/CN-6/2004 x A/Ann Arbor/6/60 ca)

    2 Recruiting Safety, Reactogenicity, and Immunogenicity of Inactivated Influenza A/H7/N7 Vaccine in Healthy Adults
    Condition: Influenza
    Interventions: Biological: Influenza A/H7N7 Vaccine; Drug: Placebo

    3 Completed Safety Study of Pandemic Candidate Influenza Vaccines in the Elderly Population
    Condition: Influenza
    Intervention: Biological: 3 adjuvanted pandemic influenza candidate vaccines + 4 non-adjuvanted pandemic influenza candidate vaccines


    http://clinicaltrials.gov/ct2/results?term=H7+vaccine


  • 1-4): J Virol. 2007 Jul 25; [Epub ahead of print]

    The genesis and evolution of H9N2 influenza viruses in poultry from southern China, 2000 to 2005.

    Xu KM, Smith GJ, Bahl J, Duan L, Tai H, Vijaykrishna D, Wang J, Zhang JX, Li KS, Fan XH, Webster RG, Chen H, Peiris JS, Guan Y.
    International Institute of Infection and Immunity, Shantou University, Shantou, Guangdong 515031, China; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Sing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; and Virology Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
    -

    H9N2 influenza viruses have become established in terrestrial poultry in recent two decades in different Asian countries.

    Our previous study demonstrated that quail harbor increasing diversity of novel H9N2 reassortants, including both Chicken/Beijing/1/94 (Ck/Bei-like) and Quail/Hong Kong/G1/97 (G1-like) viruses.

    However, since 1999 the genesis and evolution of H9N2 viruses in different types of poultry have not been systematically investigated.

    In the present study, H9N2 viruses isolated from chicken, duck and other minor poultry were genetically and antigenically characterized.

    Our findings demonstrate that Ck/Bei-like H9N2 viruses have been introduced into many different types of poultry including quail, partridge, chukkar, pheasant, Guinea fowl and domestic duck in southern China, while the G1-like viruses were commonly detected from quail, less frequently detected in other minor poultry and not detected in chicken and duck.

    Genetic analysis revealed 35 genotypes of H9N2 viruses, including 14 novel genotypes that have not been recognized before.

    Our results also suggested that two-way interspecies transmission exist between different types of poultry.

    Our study demonstrated that the long-term co-circulation of multiple virus lineages (e.g. H5N1 and H9N2 viruses) in different types of poultry have facilitated these frequent reassortment events that were mostly responsible for current great genetic diversity of H9N2 and H5N1 influenza viruses in this region.

    This situation favors the emergence of influenza viruses with pandemic potential.
    -
    PMID: 17652402 [PubMed - as supplied by publisher]
    ------


  • (...)

    "H7, with its mildness, may be more - I hate to anthropomorphize - but more devious. Because through surreptitious spread - because it's milder, it's unrecognized, people might dismiss it more - it may actually have more opportunity to adapt to the human respiratory tract," she said from Vancouver.

    "And even though it may be mild today, even though it may not transmit easily today, the potential is always there for it to change. And basically we don't want new (flu) subtypes in the human population. We've got enough to deal with the humanized strains."
    (...)

    It is important at this point enhance surveillance but I think that out there some other viruses is smoldering for years and humans will enter in contact with them without anyone will look for.
    The sense of urgence may be understandable but perhaps there is the need of a 'paradigm change' for the entire influenza world: one pandemic strain, two pandemic strain, three or more are really traceable and preventable?
    The behaviour of scientific world in the eve of H5N1 panzootics is based on this urgence but the time goes to consume resources and attention. Is it a sustainable behaviour?
    In other words, these 'breakthough' discoveries will change the course of the events?


  • http://canadianpress.google.com/article/ALeqM5gNcxp7Ae1ILxfVkoRKTL-RTKeCGg

    North American bird flu viruses becoming more adapted to humans: study

    1 hour ago

    TORONTO — North American avian flu viruses of the H7 subtype - like the H7N3 viruses responsible for British Columbia's massive poultry outbreak in 2004 - seem to have adapted to more easily invade the human respiratory tract, a new American study suggests.

    The adaptation is still only partial and the findings do not suggest the viruses are imminently poised to trigger a pandemic. But experts say they underscore the fact that H7 flu viruses need to be watched and studied.

    "I think this is certainly amongst the most dangerous (avian flu) viruses out there," said virologist Dr. Ron Fouchier, with the Erasmus Medical Centre in Rotterdam, the Netherlands.

    "And I think we need to continue to develop vaccines for H7 just as well as H5(N1)."

    Fouchier was commenting on a scientific paper published Monday by the journal Proceedings of the National Academy of Sciences. Fouchier's research on avian influenza includes study of the H7N7 outbreak in the Netherlands in 2003, but he was not involved in this work.

    Scientists from the U.S. Centers for Disease Control reported on their research on a number of H7 viruses, looking both at the types of receptor cells - bird or human - each was more inclined to latch onto and whether the viruses transmitted from infected to uninfected ferrets.

    Of all available animal models, influenza infection in ferrets is considered to mirror most closely the course the disease takes in humans.

    Human flu viruses that circulate every winter have adapted to be able to bind to the receptors that predominate in the human respiratory tract, known as alpha 2-6 receptors. Avian viruses, on the other hand, prefer the alpha 2-3 receptors found in the guts of wild birds (their natural host) and domestic poultry. Those receptors are scarce in the human upper respiratory tract.

    It is assumed that an avian virus would need to make this kind of adaptation - learning to latch onto the human-type receptors - before it could transmit easily to and among humans.

    Among the H7 viruses the CDC scientists studied were H7N3 viruses recovered from the two British Columbians infected during an outbreak in the poultry farm-dense Fraser Valley in 2004. More than 17 million chickens were destroyed in the efforts to stop that outbreak.

    Also tested was a virus recovered from a strange H7N2 infection in the Yonkers area of New York City. A man who had no known contact with poultry was hospitalized in November 2003. Because he was suffering from other ailments, the fact that he was also harbouring an avian flu virus was not detected at the time. In fact, it was thought he had human flu.

    Several months later testing at the CDC revealed the rare infection. How the man caught the virus remains a mystery.

    Of all the H7 viruses studied for this work, the New York man's seemed most adapted to humans. It bound more easily to the receptors found in the lining of the human upper respiratory tract and had decreased binding to bird receptor cells. And when ferrets were inoculated with the virus, it spread from the infected animals to healthy animals placed in the same cages.

    But in general H7 viruses from North America that have been isolated from about 2002 onwards seem to have developed an increasing affinity for the human-type receptors, said Dr. Terrence Tumpey, the CDC scientist who led the work.

    "These viruses are partially adapted to recognize the receptors preferred by human influenza viruses, but not completely," he said in an interview from Atlanta.

    "It needs to be adapted further. But I think it shows that potentially that these viruses are changing."

    "Because we can look at an older North American H7 or Eurasian H7s or H5s and they have the characteristic avian influenza binding properties. Whereas these seem to be different and possibly changing."

    At this point it is unclear what additional changes would be needed for an H7 virus to fully adapt to a human host - or whether H7 viruses could acquire all those changes.

    When H7 viruses have caused human cases, the ensuing disease has typically been mild, with people suffering conjunctivitis (pink eye) and-or mild respiratory symptoms. There is one exception - a veterinarian infected with an H7N7 virus died during the Dutch outbreak.

    The mildness of the disease may have lulled some people into a sense of complacency about H7 viruses, said Dr. Danuta Skowronski, an influenza expert at the British Columbia Centre for Disease Control.

    But she insisted the fact that H7 viruses don't induce the life-threatening disease seen in H5N1 infection doesn't mean they shouldn't be viewed as a serious pandemic threat.

    "H7, with its mildness, may be more - I hate to anthropomorphize - but more devious. Because through surreptitious spread - because it's milder, it's unrecognized, people might dismiss it more - it may actually have more opportunity to adapt to the human respiratory tract," she said from Vancouver.

    "And even though it may be mild today, even though it may not transmit easily today, the potential is always there for it to change. And basically we don't want new (flu) subtypes in the human population. We've got enough to deal with the humanized strains."


  • North American bird flu viruses becoming more adapted to humans: study

    34 minutes ago
    TORONTO — North American avian flu viruses of the H7 subtype - like the one responsible for British Columbia's massive poultry outbreak in 2004 - seem to have adapted to more easily invade the human respiratory tract, a new American study suggests.
    Experts say the findings underscore the fact that H7 flu viruses pose a significant pandemic threat and that surveillance for cases in wild birds, poultry and people ought to be a high priority.
    "I think this is certainly amongst the most dangerous (avian flu) viruses out there," said virologist Dr. Ron Fouchier, with the Erasmus Medical Centre in Rotterdam, the Netherlands.
    "And I think we need to continue to develop vaccines for H7 just as well as H5(N1)."
    Fouchier was commenting on a study published Monday by the journal Proceedings of the National Academy of Sciences. He was not involved in the work.
    Scientists from the U.S. Centers for Disease Control reported on their study of a number of H7 viruses. Among them were viruses recovered from the two people in British Columbia who became infected during an H7N3 outbreak there in 2004.
    They tested the various viruses to see which types of receptors they can latch onto - those typically found in the guts of birds, the natural host of influenza viruses or those found on the cells of the lining of the upper respiratory tract of humans.
    Human flu viruses that circulate every winter have adapted to be able to bind to the receptors that predominate in the human respiratory tract, known as alpha 2-6 receptors. Avian viruses, on the other hand, prefer the alpha 2-3 receptors found in the guts of wild birds and poultry but which are scarce in the human upper respiratory tract.
    It is assumed that an avian virus would need to make this kind of adaptation - learning to latch onto the human receptors - before it could transmit easily to humans and then among them.
    H7 viruses from North America that have been isolated from about 2002 onwards seem to have developed an increasing affinity for the human-type receptors, said Dr. Terrence Tumpey, the CDC scientist who led the work.
    "These viruses are partially adapted to recognize the receptors preferred by human influenza viruses, but not completely," he said in an interview from Atlanta.
    "It needs to be adapted further. But I think it shows that potentially that these viruses are changing."
    "Because we can look at an older North American H7 or Eurasian H7s or H5s and they have the characteristic avian influenza binding properties. Whereas these seem to be different and possibly changing."
    At this point it is unclear what additional changes would be needed for an H7 virus to fully adapt to a human host. And whatever the changes are, scientists cannot say whether the virus could ever acquire all of them.
    When H7 viruses have caused human cases, the ensuing disease has typically been mild, with people suffering conjunctivitis (pink eye) and-or mild respiratory symptoms. There is one exception - a veterinarian infected with an H7N7 virus died during an outbreak in the Netherlands in the spring of 2003.
    The mildness of the disease may have lulled some people into a sense of complacency about H7 viruses, said Dr. Danuta Skowronski, an influenza expert at the British Columbia Centre for Disease Control.
    But she insisted the fact that the virus doesn't induce the life-threatening disease seen in H5N1 infection doesn't mean it shouldn't be taken seriously as a pandemic threat.
    "H7, with its mildness, may be more - I hate to anthropomorphize - but more devious. Because through surreptitious spread - because it's milder, it's unrecognized, people might dismiss it more - it may actually have more opportunity to adapt to the human respiratory tract," she said from Vancouver.
    "And even though it may be mild today, even thought it may not transmit easily today, the potential is always there for it to change. And basically we don't want new (flu) subtypes in the human population. We've got enough to deal with the humanized strains."

    http://canadianpress.google.com/article/ALeqM5gNcxp7Ae1ILxfVkoRKTL-RTKeCGg


  • (1.1): Arch Virol. 2007 Nov 15; [Epub ahead of print]

    Genetic analysis of four porcine avian influenza viruses isolated from Shandong, China.

    Shi WF, Gibbs MJ, Zhang YZ, Zhang Z, Zhao XM, Jin X, Zhu CD, Yang MF, Yang NN, Cui YJ, Ji L. - Institute of Life Sciences, Taishan Medical College, Shandong Tai’an, China.
    A Bayesian phylogenetic analysis of eight separate gene segments indicated A/Swine/Shandong/2/2003 (H5N1), A/Swine/Shandong/na/2003 (H9N2), A/Swine/Shandong/nb/2003 (H9N2) and A/Swine/Shandong/nc/2005 (H9N2) probably represent two multiple reassortant lineages, that had not been described before, with genes coming from H5N1, H9N2 and other lineages from poultry in Asia.

    Amino acid motifs within the haemagglutinin sequence of A/Swine/Shandong/nb/2003 suggested it may be able to infect people, whereas the sequences of the other three isolates suggested they would not have had that capability.

    Our analysis emphasizes the need for a comprehensive study of the interactions between H5N1 and H9N2 viruses in Asia that includes sequencing and phylogenetic investigation.
    PMID: 18000640 [PubMed - as supplied by publisher]
    -----


  • (1-4): J Gen Virol. 2007 Jul;88(Pt 7):2035-41.

    Antigenic and genetic characterization of H9N2 swine influenza viruses in China.
    Cong YL, Pu J, Liu QF, Wang S, Zhang GZ, Zhang XL, Fan WX, Brown EG, Liu JH.
    Laboratory of Infectious Diseases, College of Veterinary Medicine, State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, PR China.
    -

    As pigs are susceptible to infection with both avian and human influenza A viruses, they have been proposed to be an intermediate host for the generation of pandemic virus through reassortment.

    Antigenic and genetic characterization was performed for five swine H9N2 influenza viruses isolated from diseased pigs from different farms.

    The haemagglutinin (HA) antigenicity of swine H9N2 viruses was different from that of chicken H9N2 viruses prevalent in northern China.

    Genetic analysis revealed that all five isolates had an RLSR motif at the cleavage site of HA, which was different from those of A/duck/Hong Kong/Y280/97 (Dk/HK/Y280/97)-like viruses established in chickens in China.

    Phylogenetic analyses indicated that the five swine H9N2 viruses formed novel HA and neuraminidase sublineages that were related closely to those of earlier chicken H9 viruses and were also consistent with the extent of the observed antigenic variation.

    The six internal genes of the isolates possessed H5N1-like sequences, indicating that they were reassortants of H9 and H5 viruses.

    The present results indicate that avian to porcine interspecies transmission of H9N2 viruses might have resulted in the generation of viruses with novel antigenic and genetic characteristics; therefore, surveillance of swine influenza should be given a high priority.
    -
    PMID: 17554038 [PubMed - in process]
    -----


  • So, do we have the only publicly available set of these sequences?
    I am looking for replacement sequences, but haven't found them yet. The links still work for the sequences, but finding the sequences without the links is a challenge because they are not in the main database.


  • This just goes to show that any avian flu has the potential to become pandemic.


  • CDC has pulled sequences

    http://www.flutrackers.com/forum/showpost.php?p=152098&postcount=1


  • Source: http://www.timesonline.co.uk/tol/news/uk/science/article4009755.ece
    From The Times
    May 27, 2008
    Scientists identify second H7 strain of bird flu that could cause pandemic

    Mark Henderson, Science Editor

    The H5N1 strain of bird flu that has killed 241 people is not the only one that could trigger a pandemic, according to research in America. A few H7 strains of the flu virus have started to evolve some of the traits they would need to infect people easily, scientists have discovered.

    The findings, from a team led by Terrence Tumpey, of the US Centres for Disease Control and Prevention (CDC) in Atlanta, show that while there is no immediate indication that H7 flu is about to acquire potentially damaging mutations, it is critical that global surveillance and research covers this virus class as well as the more obvious H5N1, scientists said.

    The H5N1 strain has been regarded as the most deadly strain since it appeared in Asia in 2003. Although it has a death rate of more than 60 per cent, it has not yet acquired the ability to move from person to person, which would be a prerequisite for a pandemic.

    There has been only one case in which it is considered probable that the virus was transmitted from person to person, and analysis of the virus's genetic structure has not yet revealed mutations that would allow it to infect people more easily. It is generally caught from close contact with infected birds, in which it is endemic in some parts of the world, particularly in Asia.

    The H7 family of flu viruses also primarily affects birds. A deadly version of the H7N7 strain hit poultry in the Netherlands in 2003, and a less severe form, H7N2, broke out in the UK last year. Between 2002 and 2004 several outbreaks of H7N3 and H7N2 have been reported.

    In each of these incidents a few human cases of infection have been reported. One vet died during the Dutch outbreak and about 80 people suffered conjunctivitis, an eye infection that is not life-threatening.

    The UK outbreak also led to cases of conjunctivitis and a few mild respiratory infections.

    Dr Tumpey's analysis of a 2003 case in New York has shown, however, that the H7N2 virus responsible is capable of replicating in the respiratory tract of mammals. This quality is unusual among avian viruses, and indicates that it could possibly be transmissible from person to person.

    A study with ferrets — a standard animal model of flu in humans — also revealed that this H7N2 strain could be passed from animal to animal.

    This suggests that the virus could be acquiring an ability to bind to sugars found on the cells of the human windpipe. This happened during all three of the 20th-century flu pandemics, which occurred in 1918, 1957 and 1968. “These findings suggest that the H7 class of viruses are partially adapted to recognise the receptors that are preferred by the human influenza virus,” Dr Tumpey said.

    “The finding ... underscores the necessity for continued surveillance and study of these viruses as they continue to resemble viruses with pandemic potential.”

    Each of the three flu pandemics of the last century was caused by a humanised strain of flu. The Spanish Flu of 1918-19, which killed up to 40 million people, was caused by an H1N1 virus. The 1957-58 Asian Flu was caused by an H2N2 strain, and the 1968-69 Hong Kong Flu by an H3N2 strain.

    Plague proportions

    — Flu strains are categorised according to two key proteins, called haemagglutinin (H) and neuraminidase (N)

    — The strain currently endemic in birds in many parts of the world, particularly in Asia, is H5N1

    — A first solid case of human-to-human transmission, between a father and son in China, was reported last month

    — Other avian strains of flu that could prove threatening to people include the H7 family, the subject of the new research

    — Defences are largely reliant on antiviral drugs, particularly Tamiflu. The UK has ordered sufficient courses to cover 30 million people

    — The Government says that up to 750,000 people could die in a pandemic, though a figure of 150,000-375,000 is thought likelier

    Source: Times Database


  • http://www.recombinomics.com/News/04280802/H7N2_NY_Reassortant.html

    http://www.recombinomics.com/News/04280803/H7N2_NY_Reassortant_Concerns.html

    http://www.recombinomics.com/News/04290801/H7N2_NY_Reassortant_Ferrets.html


  • Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

    Jessica A. Belser*,, Ola Blixt, Li-Mei Chen*, Claudia Pappas*, Taronna R. Maines*, Neal Van Hoeven*, Ruben Donis*, Julia Busch, Ryan McBride, James C. Paulson, Jacqueline M. Katz*, and Terrence M. Tumpey*,

    *Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Emory University, Atlanta, GA 30322; and Departments of Physiological Chemistry and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037

    Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved March 21, 2008 (received for review February 7, 2008)

    Avian H7 influenza viruses from both the Eurasian and North American lineage have caused outbreaks in poultry since 2002, with confirmed human infection occurring during outbreaks in The Netherlands, British Columbia, and the United Kingdom.

    The majority of H7 infections have resulted in self-limiting conjunctivitis, whereas probable human-to-human transmission has been rare.

    Here, we used glycan microarray technology to determine the receptor-binding preference of Eurasian and North American lineage H7 influenza viruses and their transmissibility in the ferret model.

    We found that highly pathogenic H7N7 viruses from The Netherlands in 2003 maintained the classic avian-binding preference for 2–3-linked sialic acids (SA) and are not readily transmissible in ferrets, as observed previously for highly pathogenic H5N1 viruses.

    However, H7N3 viruses isolated from Canada in 2004 and H7N2 viruses from the northeastern United States isolated in 2002–2003 possessed an HA with increased affinity toward 2–6-linked SA, the linkage type found prominently on human tracheal epithelial cells.

    We identified a low pathogenic H7N2 virus isolated from a man in New York in 2003, A/NY/107/03, which replicated efficiently in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact.

    These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and have the potential to spread to naïve animals.
    -
    http://www.pnas.org/cgi/content/short/105/21/7558?rss=1
    ------


  • can we find a referrence to that H9 virus with H5N1 internal genes ?
    Was it virulent ?


    -----edit1------------

    http://vir.sgmjournals.org/cgi/content/abstract/88/7/2035


  • Evolution of flu strains points to higher risk

    (AFP)

    26 May 2008


    But one strain of the H7N2 virus, a low pathogenic avian flu strain isolated from a man in New York in 2003, replicated in the ferret's respiratory tract and was passed between infected and uninfected ferrets suggesting it could be transmissible in humans.



    http://www.khaleejtimes.com/DisplayArticleNew.asp?xfile=data/theworld/2008/May/theworld_May1165.xml§ion=theworld
    This is a human / avian reassortant

    http://www.recombinomics.com/News/04280802/H7N2_NY_Reassortant.html


  • And from Avian Flu Diary . . .

    Study: H7 Strains Evolving

    # 2019

    What little media attention we've seen surrounding pandemic flu over the past few years has been largely focused on the H5N1 bird flu virus. Scientists know, however, that there are other influenza's out there in the running to spark the next pandemic.

    The H7 virus, while a dark horse candidate, has already made a small number of campaign appearances.


    The following is a list of known of human H7 infections since 2002 (stats borrowed from CIDRAP's (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/) Summary of Avian Influenza Cases in Humans (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html))

    2002 H7N2 1 case United States (Virginia) Evidence of infection was found in one person in Virginia following a poultry outbreak

    2003 H7N7 89 cases (1 death) The Netherlands During an outbreak of H7N7 avian influenza in poultry, infection spread to poultry workers and their families in the area (see References (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html#_Influenza_Pandemics_of): Fouchier 2004, Koopmans 2004, Stegeman 2004). Most patients had conjunctivitis and several complained of influenza-like illness. The death occurred in a 57-year-old veterinarian. Subsequent serologic testing demonstrated that additional case-patients had asymptomatic infection.

    2003 H7N2 1 New York The source of exposure was not determined

    2004 H7N3 2 cases Canada (British Columbia) Two poultry workers became ill during an outbreak of H7N3 avian influenza in poultry (see References (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html#_Influenza_Pandemics_of): Health Canada 2004). Both had conjunctivitis.
    And 4 people were confirmed to have contracted H7N2 in the UK last year. . . . .

    http://afludiary.blogspot.com/2008/05/study-h7-strains-evolving.html

    Elsewhere in the world other LPAI A/H7 strain caused human infections.

    Last year LPAI A/H7N2 in Wales is one of these examples, although phylogenetic distance between North-American strain and European one may be substantial.

    See WHO European Regional Office update (2007):
    -
    Human cases of avian influenza A/H7N2 in the United Kingdom

    Following the confirmation on 25 May 2007 by Health Authorities of the United Kingdom, of influenza A/H7N2 virus infection in four individuals (two in Wales and two in north-west England) exposed to infected poultry at smallholding, Corwen Farm, Conwy, Wales, the National Public Health Service (NPHS) for Wales is continuing with the investigation of the incident and with the implementation of public health measures.

    As of 30 May 2007, 256 individuals, exposed either to affected premises, infected poultry, or to another individual with confirmed or presumptive influenza A/H7N2 virus infection, were identified in the following settings: household (39), school (14), and workplace setting (203), including, at least, 148 patients and staff at two hospitals.

    Seventy-nine (79) of the exposed individuals are no longer considered at risk as the 7 days incubation period has elapsed.

    As a precautionary measure, and in accordance with UK policy, the decision was made to offer oseltamivir to exposed individuals.

    In addition to the two Wales residents with laboratory confirmed infection, 17 of the exposed individuals, including one health care worker, present or have presented with influenza-like illness (fever above 38° C, aches and pains, cough/head cold, sore throat or conjunctivitis).

    None of them is seriously ill and they are receiving and have received oseltamivir treatment.

    Nose, throat, and eyes swabs obtained from 12 individuals tested negative for influenza A/H7N2 virus infection.

    Although according to the preliminary results of the epidemiological investigation, limited human-to-human transmission can not be ruled out, the public health risk is considered low.

    There is very limited evidence of human-to-human transmission associated with low pathogenic avian influenza viruses like influenza A/H7N2 virus.

    However, this was documented by a retrospective cohort study conducted in Netherlands in 2003 and in relation to the highly pathogenic influenza A/H7N7 virus outbreak in poultry.
    -
    http://www.euro.who.int/flu/situation/20070601_1
    -----


  • I remember when Webster in mid 2006 at the height of the H5N1-concern
    said, that he currently examines H9N2, which might cause a pandemic too,
    is another hot candidate.

    This gave me some relief after he just had said : 50% likelyhood of a H5N1-pandemic
    and 50% of the world's population could die.

    Nothing special with H9N2, no WHO-alert-level, it has been around since long
    so the danger should be as it was the last centuries (or not ?)

    So Webster did put H5N1 in the same category a H9N2, also his semi-retraction
    and not repeating the 50% statement, which made me feel a little more easy in
    later 2006 than I had felt in early 2006 until the Karo cluster.

    Now, H7 has been documented in 1902 as "fowl plague" and reports back to 1870
    about fowl plague were probably also H7. No problems for humans ever.
    Why now ?

    I can see the changes with H5N1 since 1997, but what's new with H7 ?

    I don't put in discussion the great work of professor Webster and his recent statement at a thailandese meetings, according the Science review. He said that the H5N1 worries him less than five years ago. But perhaps the reporter didn't understand well the word. Sometimes happens that a statement by a person is reported in a wrongly way, without precise context...

    Chinese researchers studied H9N2 virus and found that a reassortants emerged, with surface protein fron H9 and internal segments from H5N1. But are there international health officials concerned for this development? Who cares for it?

    As said, perhaps there is a lack of comprehensive knowledge of ecological behaviour for these viruses. Possibly harmful for humankind.
    ----
    From Science:
    (...)
    BANGKOK—Just a couple of years ago, scientists, public health officials, and journalists were nervously tracking every move of
    the deadly H5N1 avian influenza virus, fearing that a few simple mutations might give it the ability to spread readily among
    humans, sparking a global pandemic that could kill tens of millions. But since alarms were sounded when the virus started
    spreading in earnest among birds in late 2003, the dreaded pandemic hasn’t come.

    “I’m less worried about this virus than I was 5 years ago,” says virologist Robert Webster of St. Jude Children’s Research
    Hospital in Memphis, Tennessee. (...)
    ( 29 FEBRUARY 2008 - VOL 319 - SCIENCE - www.sciencemag.org (http://www.sciencemag.org) )


  • Evolution of flu strains points to higher risk

    (AFP)

    26 May 2008

    CHICAGO - Some strains of bird flu are coming ever closer to developing the traits they need to cause a human pandemic, a study released Monday said.

    Researchers who analysed samples of recent avian flu viruses found that a few H7 strains of the virus that have caused minor, untransmissible infections in people in North America between 2002 and 2004 have increased their affinity for the sugars found on human tracheal cells.

    Subsequent tests in ferrets suggested that these viral strains were not readily transmissible.

    But one strain of the H7N2 virus, a low pathogenic avian flu strain isolated from a man in New York in 2003, replicated in the ferret's respiratory tract and was passed between infected and uninfected ferrets suggesting it could be transmissible in humans.

    The investigators said the evidence suggests that the virus could be evolving toward the same strong sugar-binding properties of the three worldwide viral pandemics in 1918, 1957 and 1968.

    "These findings suggest that the H7 class of viruses are partially adapted to recognize the receptors that are preferred by the human influenza virus," said Terrence Tumpey, a senior microbiologist with the US Centers for Disease Control and Prevention in Atlanta.

    The authors said that if the viruses continue to evolve in this direction, the avian flu viruses could travel more easily between other animals and humans. They called for strict surveillance of avian flu viruses and continuing federal preparations for a possible future pandemic.

    The study appears in the Proceedings of the National Academy of Sciences.


    http://www.khaleejtimes.com/DisplayArticleNew.asp?xfile=data/theworld/2008/May/theworld_May1165.xml§ion=theworld
    -
    Pathogenesis of avian influenza (H7) virus infection in mice and ferrets: enhanced virulence of Eurasian H7N7 viruses isolated from humans.
    Belser JA, Lu X, Maines TR, Smith C, Li Y, Donis RO, Katz JM, Tumpey TM.
    Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, MS G-16, 1600 Clifton Rd. NE, Atlanta, GA 30333, USA.

    Before 2003, only occasional case reports of human H7 influenza virus infections occurred as a result of direct animal-to-human transmission or laboratory accidents; most of these infections resulted in conjunctivitis.

    An increase in isolation of avian influenza A H7 viruses from poultry outbreaks and humans has raised concerns that additional zoonotic transmissions of influenza viruses from poultry to humans may occur.

    To better understand the pathogenesis of H7 viruses, we have investigated their ability to cause disease in mouse and ferret models.

    Mice were infected intranasally with H7 viruses of high and low pathogenicity isolated from The Netherlands in 2003 (Netherlands/03), the northeastern United States in 2002-2003, and Canada in 2004 and were monitored for morbidity, mortality, viral replication, and proinflammatory cytokine production in respiratory organs.

    All H7 viruses replicated efficiently in the respiratory tracts of mice, but only Netherlands/03 isolates replicated in systemic organs, including the brain.

    Only A/NL/219/03 (NL/219), an H7N7 virus isolated from a single fatal human case, was highly lethal for mice and caused severe disease in ferrets.

    Supporting the apparent ocular tropism observed in humans following infection with viruses of the H7 subtype, both Eurasian and North American lineage H7 viruses were detected in the mouse eye following ocular inoculation, whereas an H7N2 virus isolated from the human respiratory tract was not.

    Therefore, in general, the relative virulence and cell tropism of the H7 viruses in these animal models correlated with the observed virulence in humans.

    PMID: 17686867 [PubMed - indexed for MEDLINE]
    PMCID: PMC2045519
    -
    http://www.ncbi.nlm.nih.gov/pubmed/17686867?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum
    ------


  • Mild American Bird-Flu Strains Gained Ability to Attack Humans
    By John Lauerman
    May 26 (Bloomberg) -- Mild bird flu strains circulating in North America have gained some ability to infect human cells, and should be monitored for dangerous mutations, government researchers said.
    The virus family, called H7, is genetically different than the H5N1 strain that has killed millions of birds and hundreds of people, said Terrence Tumpey, a U.S. Centers for Disease Control and Prevention scientist in Atlanta. More mutations in the H7 strain could make it dangerous to humans, he said.
    People don't have natural immunity to many strains of flu spreading in birds, allowing these viruses to cause severe infections when they enter human cells. Some strains of H7 have increased their ability to stick to proteins on the surface of human lung cells, a key step in infection that may at some point allow its spread from one human to another, Tumpey said in a study in the Proceedings of the National Academy of Sciences journal.
    ``This underscores the importance of continued surveillance so we can be best prepared for early response to a pandemic threat,'' he said in a telephone interview.
    At least 241 people have died of H5N1 bird flu since 2003, most of them in Asia. A worldwide network of laboratories collects and analyzes samples for mutations that might allow the virus to spread quickly from person to person.
    Tumpey analyzed H7 viruses that infected poultry and people from 2002 through 2004. One was an H7 strain that caused an outbreak in the Netherlands in 2003, infecting about 80 people and killing one person.
    Eye Infections
    That strain wasn't well adapted to human lung cells, and most human infections were in the eye, Tumpey said. His analysis showed the virus prefers attaching to a molecule in birds' intestines, called alpha 2-3.
    Other H7 strains circulating at the same time in Canada and the U.S., however, had the ability to attach to a cell surface molecule called alpha 2-6. That molecule is found in the breathing tissues of humans and animals, and is a common target for seasonal flu viruses that cause annual outbreaks and spread quickly through the population, he said.
    One H7 strain that infected a New York man in 2004 was easily transmitted among ferrets, the study showed. Ferrets and humans are susceptible to many of the same flu viruses.
    While the finding is important, other characteristics probably contribute to the ability of viruses to spread and make people ill, said Albert Osterhaus, a virologist at the Erasmus Medical Center in Rotterdam. Other factors, such as whether the virus grows in the human nose and throat, rather than deep in the lungs, may allow it to spread quickly, he said.
    Respiratory Tract
    ``Those that replicate in the upper respiratory tract are more likely to be transmitted between mammals,'' he said in a telephone interview. The ability to bind to human cells ``is not the whole story.''
    While these H7 viruses are ``low pathogenic,'' meaning they rarely cause deaths, they nonetheless pose a threat, Tumpey said.
    ``We have to be aware of these viruses just like we're aware of H5 viruses,'' he said. ``They have the potential to mutate to high pathogenic and they are in our backyard.''
    Three influenza pandemics occurred last century in 1918, 1957 and 1968. The most lethal by far was the 1918 ``Spanish flu'' that killed as many as 50 million people worldwide.
    To contact the reporter on this story: John Lauerman in Boston at jlauerman@bloomberg.net .
    Last Updated: May 26, 2008 17:00 EDT

    http://www.bloomberg.com/apps/news?pid=washingtonstory&sid=aVWZxrgJpeo0


  • Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

    Jessica A. Belser*,, Ola Blixt, Li-Mei Chen*, Claudia Pappas*, Taronna R. Maines*, Neal Van Hoeven*, Ruben Donis*, Julia Busch, Ryan McBride, James C. Paulson, Jacqueline M. Katz*, and Terrence M. Tumpey*,

    *Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Emory University, Atlanta, GA 30322; and Departments of Physiological Chemistry and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037

    Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved March 21, 2008 (received for review February 7, 2008)

    Avian H7 influenza viruses from both the Eurasian and North American lineage have caused outbreaks in poultry since 2002, with confirmed human infection occurring during outbreaks in The Netherlands, British Columbia, and the United Kingdom.

    The majority of H7 infections have resulted in self-limiting conjunctivitis, whereas probable human-to-human transmission has been rare.

    Here, we used glycan microarray technology to determine the receptor-binding preference of Eurasian and North American lineage H7 influenza viruses and their transmissibility in the ferret model.

    We found that highly pathogenic H7N7 viruses from The Netherlands in 2003 maintained the classic avian-binding preference for 2–3-linked sialic acids (SA) and are not readily transmissible in ferrets, as observed previously for highly pathogenic H5N1 viruses.

    However, H7N3 viruses isolated from Canada in 2004 and H7N2 viruses from the northeastern United States isolated in 2002–2003 possessed an HA with increased affinity toward 2–6-linked SA, the linkage type found prominently on human tracheal epithelial cells.

    We identified a low pathogenic H7N2 virus isolated from a man in New York in 2003, A/NY/107/03, which replicated efficiently in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact.

    These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and have the potential to spread to naïve animals.
    -
    http://www.pnas.org/cgi/content/short/105/21/7558?rss=1
    ------
    Earlier commentary

    http://www.recombinomics.com/News/04290801/H7N2_NY_Reassortant_Ferrets.html







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