Currently it has been found after large-scale, exhaustive sequence analysis of avian Influenza A virus isolates that the PB1-F2 transcript is under the highest positive selective pressure for nonsynonymous substitutions [28]. This combined with the emerging threat of a possible human pandemic of Influenza A virus brings the enhancement of pathogenicity by PB1-F2 to the forefront. The World Health Organization's (WHO) policy now is to recommend the stockpiling of antibiotics to combat secondary bacterial infections associated with an outbreak of pandemic Influenza A virus [29]. If one could also develop an antiviral antagonist of the PB1-F2 protein (especially due to its ability to induce macrophage apoptosis when present extracellularly) the targeted destruction of professional antigen presenting cells could be inhibited. Therefore, the ability to clear virus and more importantly to fend off opportunistic bacterial infections would be maintained. The inhibition of PB1-F2 could prove to have a profound effect on human health because this could reduce the high rates of mortality associated with pandemic and epidemic Influenza A viruses carrying this alternate reading frame.
Acknowledgements
The author would like to thank Lisa M. Runco for her editorial advice. Also the author is supported in part by The American Foundation for Aging Research.
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