By: David M. Moran, et al; National Institute of Allergy and Infectious Diseases
28 September 2010
History suggests that the 2009 pandemic H1N1 influenza virus faces extinction unless it mutates to avoid already high global population immunity. The immune escape mechanisms potentially at its disposal include antigenic drift, antigenic shift via genetic reassortment, and intrasubtypic reassortment. Going back to the late 19th century, the evolutionary histories of past pandemic viruses are examined in an effort to better understand the nature and extent of the immune pressures faced by the 2009 pandemic virus in the immediate future. While human influenza viruses have often surprised us, available evidence leads to the hope that the current pandemic virus will continue to cause low or moderate mortality rates if it does not become extinct.
We have little information concerning the determinants of the capacity for antigenic drift. We do not know whether this capacity is inherent in all influenza viruses or a chance property of the founding viral HA such as mutational repertoire or the ability to add HA glycosylation to achieve antigenic masking. Nor is it known how likely reassortment with antigenic shift is for viruses inherently unable, or no longer able, to escape immunity via successful antigenic drift. With respect to H1N1 viruses, we do not understand how and why a slowly drifting and relatively avirulent virus like seasonal H1N1 reemerged in 1977 in a partially immune population from which it had disappeared entirely with the emergence of the 1957 H2N2 virus 20 years earlier (Fig. 2) (17). We do not understand how, after initially infecting only individuals under 20 years of age, it continued to circulate with minimal drift up immunity.
Related questions include how and why high population immunity has been associated with rapid seasonal H3N2 drift, but with only slow seasonal H1N1 drift, and why such conditions have not resulted in H1N1 extinction. Other factors to be addressed include the potential impact of various global infection and vaccination experiences on the evolution of pH1N1. In this regard, most of the global population has far lower rates of pH1N1 and seasonal influenza vaccination and influenza virus circulation patterns differ globally.
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