The World Health Organization (WHO) recently announced that genetic changes in H1N1 (swine flu) discovered in viral isolates from Ukraine and other countries – including the United States – were not “…leading to an unusual increase in the number of H1N1 infections or a greater number of severe or fatal cases.” WHO attributed these changes to “random mutation” and implied that the genetic variants were unlikely to quickly spread. (World Health Organization. Public health significance of virus mutation detected in Norway. Pandemic (H1N1) 2009 briefing note 17. November 20, 2009)
However, prominent virologists, including Henry Niman, PhD, of Recombinomics, Incorporated, disagree with WHO’s assessment. Indeed, some experts feel that 2009 H1N1 has acquired characteristics that make it very similar to the pandemic “Spanish” flu of 1918 – 1919; furthermore, they believe these genetic characteristics, called polymorphisms, were acquired via recombination, or genetic “sharing” between viruses.
In contrast to random mutations, polymorphisms that are acquired by recombination are more likely to have been present in the viral population for extended periods of time. Thus, they have been subjected to evolutionary pressures and have survived through multiple generations of viral replication.
Hence, recombinant polymorphisms probably confer a survival benefit to those viruses that possess them. Such evolutionary advances may include the ability to more easily spread from one host to another, to more quickly replicate in a specific tissue in the body, or to evade the host’s immune system.
Tamiflu Resistance and the H274Y Polymorphism
Widespread resistance to oseltamivir (Tamiflu) developed relatively quickly in seasonal influenza viruses (H1N1, H3N2). Initially, Tamiflu resistance linked to the H274Y polymorphism was noted in areas where the drug was in common use for treating victims of influenza – a not unusual development among viruses and bacteria that are exposed to antimicrobial drugs.
However, because this polymorphism conferred survival benefit to seasonal influenza viruses, it soon showed up among viruses in places where Tamiflu had not been previously dispensed (i.e., via recombination). (Niman H. Emergence and fixing of antiviral resistance in influenza A via recombination and hitchhiking. February 2009. Recombinomics, Inc, Pittsburgh, Pennsylvania, USA)
Since seasonal flu viruses commonly co-infect individuals who have been exposed to 2009 H1N1, the opportunity for these viruses to share polymorphisms has allowed 2009 H1N1 to acquire H274Y in many areas. As time passes, Tamiflu resistance in 2009 H1N1 influenza will become more problematic.
Hemorrhagic Pneumonia and the D225G Polymorphism
A more alarming change now being detected in 2009 H1N1 is the emergence of the D225G polymorphism. This alteration in swine flu’s receptor binding domain (the “hook” that allows the virus to infect human cells) is the same polymorphism found in strains of the Spanish flu from New York and London in 1918 – 1919.
D225G was detected among 2009 H1N1 strains isolated from patients in Ukraine after these individuals died from hemorrhagic pneumonia, a particularly aggressive form of influenza. The World Health Organization was slow to acknowledge this discovery and minimized its importance.
Unfortunately, D225G has subsequently been identified in other patients suffering from severe and fatal H1N1 infections in Norway, Brazil, China, Japan, Mexico, France, and the U.S. Many of these patients were ill as long ago as July and August, 2009.
D225G apparently confers a “tropism” for human lung epithelial cells – that is, the virus preferentially binds to, enters, and replicates in lung cells – that eventually evokes a “cytokine storm” and leads to destruction of lung tissue.
Notably, D225G may allow viruses that carry the polymorphism to evade early immune detection. Some D225G isolates from Ukraine have exhibited low immune reactivity in laboratory antigenicity studies, indicating not only the ability to sidestep immune surveillance, but also foretelling of difficulties in vaccine development.
Even more ominous, recent H1N1-related fatalities have involved viruses that carry both the D225G and H274Y polymorphisms. In other words, some 2009 H1N1 strains are capable of evading the early immune response, readily infecting human lung cells, and evoking a cytokine storm that destroys lung tissue. And they are resistant to Tamiflu, the drug stockpiled by most nations in an effort to blunt the effects of an influenza pandemic.
Viruses adapt quickly; their continued survival depends on an innate ability to cope with evolutionary pressures and move from one host to another. With the emergence of drug-resistant and increasingly virulent forms of influenza viruses, countries around the globe are ill-prepared for the inevitable.
Stephen Allen Christensen - Dr. Steve Christensen's writing has appeared in magazines, professional journals, poetry anthologies, and children's books since 1976.
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