Abstract

The swine-origin influenza A (H1N1) virus that appeared in 2009 and was first found in human beings in Mexico, is a reassortant with at least three parents. Six of the genes are closest in sequence to those of H1N2 'triple-reassortant' influenza viruses isolated from pigs in North America around 1999-2000. Its other two genes are from different Eurasian 'avian-like' viruses of pigs; the NA gene is closest to H1N1 viruses isolated in Europe in 1991-1993, and the MP gene is closest to H3N2 viruses isolated in Asia in 1999-2000. The sequences of these genes do not directly reveal the immediate source of the virus as the closest were from isolates collected more than a decade before the human pandemic started. The three parents of the virus may have been assembled in one place by natural means, such as by migrating birds, however the consistent link with pig viruses suggests that human activity was involved. We discuss a published suggestion that unsampled pig herds, the intercontinental live pig trade, together with porous quarantine barriers, generated the reassortant. We contrast that suggestion with the possibility that laboratory errors involving the sharing of virus isolates and cultured cells, or perhaps vaccine production, may have been involved. Gene sequences from isolates that bridge the time and phylogenetic gap between the new virus and its parents will distinguish between these possibilities, and we suggest where they should be sought. It is important that the source of the new virus be found if we wish to avoid future pandemics rather than just trying to minimize the consequences after they have emerged. Influenza virus is a very significant zoonotic pathogen. Public confidence in influenza research, and the agribusinesses that are based on influenza's many hosts, has been eroded by several recent events involving the virus. Measures that might restore confidence include establishing a unified international administrative framework coordinating surveillance, research and commercial work with this virus, and maintaining a registry of all influenza isolates.

Highlights

  • A novel H1N1 influenza virus, Swine-Origin Influenza Virus (S-OIV), was first isolated in mid-April 2009 and, by the end of the month, the first complete genomic sequences were published, and the virus shown to be of a novel re-assortant [1]

  • Virology Journal 2009, 6:207 http://www.virologyj.com/content/6/1/207 discuss its genealogy deduced from its gene sequences, it seems that we have no clearer evidence of its immediate origins than we have of the influenzas that caused past influenza pandemics

  • At least two contrasting theories are congruent with this possibility and the available clues: 1) The "unsampled pig herd" theory was suggested by Smith and his colleagues [8], who concluded that "the progenitor of the S-OIV epidemic originated in pigs", and the "long unsampled history observed for every segment" of the S-OIV genome "suggests that the reassortment of Eurasian and North American swine lineages may not have occurred recently, and it is possible that this single reassortant lineage has been cryptically circulating rather than two distinct lineages of swine flu", and that "Movement of live pigs between Eurasia and North America seems to have facilitated the mixing of diverse swine influenzas, leading to the multiple reassortment events associated with the genesis of the S-OIV strain."

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Summary

Introduction

A novel H1N1 influenza virus, Swine-Origin Influenza Virus (S-OIV), was first isolated in mid-April 2009 and, by the end of the month, the first complete genomic sequences were published, and the virus shown to be of a novel re-assortant [1]. All studies have concluded that S-OIV emerged into the human population on a single occasion, probably around January 2009 [8,11] They agree that six of its genes, those encoding the polymerase proteins (PB2, PB1 and PA), the haemagglutinin (HA), the nucleoprotein (NP) and the non-structural proteins (NS), show a clear affinity with those of the 'triple-reassortant' influenza viruses first found in North American pigs around 1998, whereas the other two genes, those encoding the neuraminidase (NA) and matrix proteins (MP), are from the Eurasian 'avianlike' virus lineage first isolated in Europe around 1979 [12,13,14,15,16,17,18,19]. Viruses of both lineages have been found more recently in South East Asia [20,21], but reasortants intermediate between S-OIV and its parental lineages have not [22]

Discussion
Conclusion
Cohen J
14. Olsen CW
Findings
31. Anonymous
35. Robertson JS
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