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Unformatted text preview: Perspective The NEW ENGLAND JOURNAL of MEDICINE july 16, 2009 n engl j med 361;3 nejm.org july 16 , 2009 225 continued to contribute their genes to new viruses, causing new pandemics, epidemics, and epi- zootics (see table). The current international pandemic caused by a novel influenza A (H1N1) virus derived from two unrelated swine viruses, one of them a derivative of the 1918 human virus, 3 adds to the complexity surrounding this persistent progenitor virus, its descendants, and its several lineages (see diagram). A useful way to think about influenza A events of the past 91 years is to recognize that we are living in a pandemic era that be- gan around 1918. 4 At that time, a presumably new founding virus, containing a novel set of eight influenza genes and probably de- rived from an unidentified avian- like precursor virus, became adapt- ed to mammals; the molecular and virologic events responsible for that adaptation remain unclear. This virus caused an explosive and historic pandemic, during which humans also transmitted the virus to pigs, in which it remains in cir- culation. Ever since 1918, this te- nacious virus has drawn on a bag of evolutionary tricks to survive in one form or another, in both hu- mans and pigs, and to spawn a host of novel progeny viruses with novel gene constellations, through the periodic importation or expor- tation of viral genes (see Zimmer and Burke, pages 279–285). The 2009 H1N1 pandemic virus rep- resents yet another genetic prod- uct in the still-growing family tree of this remarkable 1918 virus. To understand what has been happening since 1918, it is help- ful to think of influenza viruses not as distinct entities but as eight-member “gene teams” that work together and must some- times trade away one or more team members to make way for new gene “players” with unique skills. In nature, avian influenza A viruses seem to exist as transient complexes of eight genes that as- semble and reassemble promis- cuously, if not randomly, in an enormous global avian reservoir. Within this reservoir, avian vi- ruses remain stably adapted to the enteric tracts of hundreds of avian species, single members of which are often simultaneously infected by multiple viruses that engage in prolific gene reassort- ment. Because of this continual reassortment, a seemingly end- less variety of new viruses with potentially new properties are continually being engineered. In- deed, thousands of unique gene The Persistent Legacy of the 1918 Influenza Virus David M. Morens, M.D., Jeffery K. Taubenberger, M.D., Ph.D., and Anthony S. Fauci, M.D. Related article, p. 279 I t is not generally appreciated that descendents of the H1N1 influenza A virus that caused the cata- strophic and historic pandemic of 1918–1919 have persisted in humans for more than 90 years and have Copyright © 2009 Massachusetts Medical Society. All rights reserved....
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