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AFD - Genetics of H5N1 & Other Flu Strains

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  • AFD - Genetics of H5N1 & Other Flu Strains

    Study: Human Adaptation Of The H5N1 Virus

    # 2128

    The receptor binding domain (RBD) of the H5N1 virus is that area of its genetic sequence that allows it to attach to, and infect, host cells. Much like a key into a padlock, the RBD must `fit' the host cell in order for it to bind.

    Different viruses have an affinity for different types of cells. That is why most viruses are selective as to what organ systems they attack, or even what species are susceptible. This explains why a virus might affect a dog, or a cat, or a bird, yet not affect humans.

    This species selectivity is known as a `host range'. Viruses generally have a fairly narrow host range.

    The H5N1 virus is adapted to attach itself to the type of receptor cells most commonly found in the intestinal and respiratory tract of birds.

    These avian receptor cells are called α-2,3 cells.

    Humans have relatively few of these α-2,3 receptor cells. Instead our respiratory tract's receptor cells are mostly of the α-2,6 variety.

    This is why the H5N1 virus doesn't readily infect humans.

    For a more detailed look at RBD's, you might want to read my essay Looking for The Sweet Spot.

    The fear has been that over time, the H5N1 virus would adapt to the human α-2,6 receptor cells, increasing significantly the chances of a pandemic.

    According to a study to be published in the August issue of the Journal of General Virology, scientists have documented how the H5N1 virus mutates once it infects a human body.

    Here is the press release for the upcoming article, then a little discussion.

    Pandemic mutations in bird flu revealed

    Contact: Lucy Goodchild
    Society for General Microbiology

    Scientists have discovered how bird flu adapts in patients, offering a new way to monitor the disease and prevent a pandemic, according to research published in the August issue of the Journal of General Virology.

    Highly pathogenic H5N1 avian influenza virus has spread through at least 45 countries in 3 continents. Despite its ability to spread, it cannot be transmitted efficiently from human to human. This indicates it is not fully adapted to its new host species, the human. However, this new research reveals mutations in the virus that may result in a pandemic.

    "The mutations needed for the emergence of a potential pandemic virus are likely to originate and be selected within infected human tissues," said Professor Dr Prasert Auewarakul from Mahidol University, Thailand. "We analyzed specific molecules called haemagglutinin on viruses derived from fatal human cases. Our results suggest new candidate mutations that may allow bird flu to adapt to humans."

    Viruses with a high mutation rate such as influenza virus usually exist as a swarm of variants, each slightly different from the others. These are called H5N1 bird flu quasispecies. Professor Dr Auewarakul and his colleagues found that some mutations in the quasispecies were more frequent than others, which indicates they may be adaptive changes that make the virus more efficient at infecting humans. Most of these mutations were found in the area required for the virus to bind to the host cell.

    "This study shows that the H5N1 virus is adapting each time it infects a human," said Professor Dr Auewarakul. "Such adaptations may lead to the emergence of a virus that can cause a pandemic. Our research highlights the need to control infection and transmission to humans to prevent further adaptations."

    The research has provided genetic markers to help scientists monitor bird flu viruses with pandemic potential. This means they will be able to detect potentially dangerous strains and prevent a pandemic. The research also gives new insights into the mechanism of the genesis of a pandemic strain.

    "Our approach could be used to screen for mutations with significant functional impact," said Professor Dr Auewarakul. "It is a new method of searching for changes in H5N1 viruses that are required for the emergence of a pandemic virus. We hope it will help us to prevent a pandemic in the future."

    When a virus infects a host, such as a bird, or a mammal, it begins to replicate at an enormous rate. It makes millions, and then billions, of copies of itself. Influenza viruses have notoriously bad quality control when it comes to making copies, and often mistakes, or mutations are produced.

    Many of these mutations will be evolutionary dead-ends, but with multiple mutations going on inside a body at the same time, the better adapted viruses will flourish and thrive.

    It is this host-driven evolution that worries scientists.

    Each human infection is viewed as another opportunity for the H5N1 virus to adapt to human receptor cells.

    This study, using virus samples from various organs removed during autopsies, showed the virus doing exactly that. Adapting each time it infects a human host.

    The good news is, the virus hasn't found the right combination to unlock our human receptor cells and unleash a pandemic.

    The bad news is, as long as it is out there infecting humans, is has another opportunity to try.

    posted by FLA_MEDIC @ 8:25 AM

  • #2
    Re: AFD - H5N1 Genetics

    Tuesday, August 12, 2008

    <!-- Begin .post --> North Sumatra Remains Under Alert

    # 2228

    Over the weekend Indonesia's Health Ministry announced that test results on 13 villagers from North Sumatra were negative, and that they were cleared of having the H5N1 bird flu virus.

    Today we learn from the Jakarta Post that local Health Department officials aren't completely ready to accept those results, and that a KLB ("extraordinary occurrence") alert status remains in place.

    The WHO (World Health Organization) investigation team reportedly remains in the village, and local officials continue to talk about this incident as if it were still a possible bird flu outbreak.

    What to make of all of this?

    Obviously, something is going on in North Sumatra, and local officials are clearly worried. After all, three people did die after the recent sudden deaths of poultry in the village of Air Batu, and 13 others were sickened enough to require hospitalization.

    There have been reports of other villagers, as well, complaining of `flu-like' symptoms, and the area reportedly has been flooded with Tamiflu.

    Whether it is bird flu or not remains to be seen, but health officials on the ground apparently are not willing to take chances.

    At least not until more test results are returned.

    This report from the Jakarta Post.

    Tuesday, August 12, 2008 5:24 PM

    N. Sumatra remains alert against bird flu outbreak

    Apriadi Gunawan , The Jakarta Post , Medan | Tue, 08/12/2008 10:17 AM | Headlines

    The North Sumatra Health Office remains on "extraordinary occurrence" (KLB) alert status following the deaths of three people and the hospitalization of 13 others believed to have contracted bird flu.

    Office head Chandra Syafei Monday said his office had imposed KLB status because it had so far not received autopsy reports to determine the causes of deaths from the Health Ministry, including results on blood samples and bodily fluid from the patients from Air Batu district in Asahan regency.

    Chandra said he personally learned that the patients' blood tests were negative for bird flu from the ministry's website, but remained wary due to the lack of an official report from the ministry.

    "So far there has yet to be any report specifying whether the three victims in Asahan were positively or negatively infected with the bird flu virus. If the results are positive, we will have to monitor the area longer," Syafei told The Jakarta Post in Medan on Monday.

    Chandra said a number of health workers were still in Asahan to monitor the situation.

    "We are on full alert to monitor developments of a bird flu outbreak in Asahan. A team from the World Health Organization is still there to investigate the case," said Chandra.

    He added that health officials were focusing on the three fatalities and the 13 current patients showing symptoms consistent with bird flu.

    Chandra said so far those involved in the investigation could not determine the causes of death of the three victims and the 13 currently hospitalized.

    "The three people died following the discovery of dead poultry, but we don't know whether or not it was the cause," Chandra added.

    Chandra said authorities had disposed of 276 infected birds in Asahan and would continue to slay birds believed to be infected with virus.

    Nearby Labuhan Ratu regency has killed 1,126 birds after seeing hundreds suddenly die in the past week.

    Labuhan Batu Vice Regent Sudarwanto said the virus had affected the poultry population in six subdistricts of North Rantau: Padang Bulan, Cendana, Lobusona, Sirandorung, Ujung Bandar and Padang Matinggi.

    Sudarwanto said his office had taken several measures to prevent the spread of the disease, such as disposing of birds, conducting public awareness campaigns and using rapid testing. It has also set up posts in bird flu-prone areas.

    "We have so far carried out various anticipatory measures to curb the virus spread, and we urge people to remain alert," Sudarwanto said.

    Interestingly, this newspaper story states that officials are awaiting `autopsy reports' and a determination of the `cause of death' of the three early victims of this outbreak.

    We've been told, repeatedly, that the first three victims were buried more than two weeks ago without testing. Autopsies are rarely done in Indonesia due to religious and social objections, and exhumations are even less likely.

    If exhumations and autopsies have actually been performed, then officials have been taking extraordinary steps (for Indonesia) to determine the cause of this outbreak.

    News reporting being what it is in Indonesia, I'll need to see the autopsy results before I believe they've been performed.

    Until we know more about what killed these 3 villagers, and sickened more than a dozen others, I'm taking some heart in the fact that local officials are willing to continue to investigate this matter, despite the bland assurances of Indonesia's Health Ministry.

    posted by FLA_MEDIC @ 7:43 AM


    • #3
      Re: AFD - Genetics of H5N1 &amp; Other Flu Strains

      Friday, August 15, 2008

      <!-- Begin .post -->

      Fluing Under The Radar

      # 2234

      Every year hundreds of millions of people come down with respiratory infections; the so-called `flu', and yet only relative handful of these patients get tested to see what kind of `flu' they have.

      Often what we believe to be influenza is, in fact, some other ILI (Influenza-Like-Illness).

      Here is how the CDC describes ILIs:

      ILI is a nonspecific respiratory illness characterized by fever, fatigue, cough, and other symptoms. The majority of ILI cases is not caused by influenza but by other viruses (e.g., rhinoviruses and respiratory syncytial virus [RSV]), adenoviruses, and parainfluenza viruses).

      Less common causes of ILI include bacteria such as Legionella spp., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Streptococcus pneumoniae. Influenza, RSV, and certain bacterial infections are particularly important causes of ILI because these infections can lead to serious complications requiring hospitalization (2--4). Yearly, adults and children can average one to three and three to six ILI, respectively

      As stated, on average, adults end up with 1 to 3 ILIs each year, and children average twice that number.

      With a population of 300 million, we probably see on the order of 1 Billion ILIs each year in the United States alone.

      Since viral infections are often mild and self-limiting, most people who contract them never seek medical care. And even if they do, doctors are generally not quick to try to identify the culprit.

      Patients are likely to have recovered before the (expensive) test results could come back.

      During the 2007-2008 Flu season, the CDC's surveillance program received and tested roughly 220,000 specimens for influenza.

      Of these :
      • 39,453 (17.9%) were positive for Influenza
      • Of 39,453 influenza viruses, 28,105 (71.2%) were influenza A viruses
      • 11,348 (28.8%) were influenza B viruses
      • 8274 (29.4%) of the 28,105 influenza A viruses have been subtyped
      • 2,173 (26.3%) were influenza A (H1) viruses and
      • 6,101 (73.7%) were influenza A (H3) viruses.

      Of the 17.9% of samples shown to have been caused by an influenza virus (A or B), less than 30% were subtyped to show the strain (H1 or H3).

      It is certainly conceivable that sporadic cases of a mild, non-standard (H1 or H3) strain of influenza could circulate during flu season without being identified, even here in the United States.

      As stated in the story below, the Hong Kong cases of H9N2 were only picked up by chance.

      Malik Peiris, a well known microbiologist and one of the heroes of the SARS outbreak in 2003, tells us that the H9N2 virus may very well be circulating, unnoticed, in some parts of the world.

      This from Reuters.

      H9N2 bird flu threat understated in humans

      HONG KONG (Reuters) - The H9N2 bird flu strain, identified as a possible pandemic threat, could be infecting more humans than commonly thought but its mild symptoms mean it often goes undetected, a leading Hong Kong bird flu expert said.

      "It's quite possible ... H9N2 is infecting humans quite a lot, much (more) than we appreciate merely because it is beyond the radar," Malik Peiris, a Hong Kong-based microbiologist, told Reuters.

      "In humans, it is very mild, so most of the time it's probably not even recognized or biologically tested," said Peiris, who has co-authored several papers on the strain in recent years.

      So far, only a handful of human H9N2 cases have been documented worldwide, including four children in Hong Kong in 2003 who suffered from mild fevers and coughs -- as well as a batch in China's Guangdong province, where people often live in close proximity to poultry, Peiris said.

      The Hong Kong cases were only picked up by chance given the city's rigorous influenza testing regime, Peiris said.

      "It's quite a silent virus, it's not highly pathogenic ... and sometimes it causes some morbidity in poultry but by and large it is just there and it's unnoticed," Peiris said of the H9N2 strain.

      (Continue. . .)

      The good news is, the H9N2 virus (thus far) has only been identified as producing mild illness in humans and it is hoped that it would generate only a mild pandemic.

      The bad news is, that a pandemic of H9N2 would do nothing to negate the threat posed by the H5N1 virus.

      It isn't as if we get a choice of one or the other.

      We could, over time, see both.

      posted by FLA_MEDIC @ 8:11 AM