ABSTRACT 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. It has been one and a half years since the emergence of the 2009 novel pandemic H1N1 influenza virus (pH1N1), which caused a global pandemic in 2009-2010 (1). As we approach the 2010-2011 influenza season in the Northern Hemisphere, it is reasonable to speculate as to what role this virus will have in the upcoming influenza season in the United States. The pH1N1 virus is still circulating throughout the world, albeit at much lower levels than during the 2009-2010 influenza season (2), and it is extremely likely that infections with pH1N1 will occur in the United States during the 2010
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