Abstract :
Influenza is a highly contagious respiratory pathogen that continues to evolve and threaten
both veterinary and human public health. Influenza A viruses are continually undergoing
molecular changes through mutations, reassortment, and, in rare instances, recombination.
While they generally cause benign enteric infection in their natural reservoir of wild aquatic
birds, they can cause catastrophic and potentially lethal disease outbreaks in humans, domestic
poultry, and pigs when they cross the host species barrier. The continuing circulation of highly
pathogenic (HP) H5N1 influenza viruses in domestic poultry in parts of Eurasia and the
emergence and global spread of pandemic H1N1 2009 are current examples of influenza
evolution. The spread of both HP H5N1 and pandemic H1N1 to multiple hosts emphasizes the
potential for continued evolution. In this review, we discuss the current understanding of
influenza A virus structure and strategies of variation, with a specific focus on the HP H5N1
and pandemic H1N1 influenza viruses. Additionally, we attempt to identify the gaps in our
knowledge of H5N1 and pandemic H1N1 influenza viruses. These gaps include (i) an
understanding of the molecular determinants of influenza virus and the host that permit
efficient transmissibility and pandemic potential, (ii) the urgent need for prospective surveillance
in apparently healthy swine, (iii) the molecular determinants of high pathogenicity in
poultry, pigs, and people, (iv) the genetic basis of host susceptibility, (v) antigenic variability,
(vi) the use of vaccine to control influenza, (vii) the role of wild birds as the reservoir of highly
pathogenic avian influenza, (viii) the problems with vaccines, (ix) seasonality, (x) co-infections,
and (xi) anti-influenza drug resistance. Our failure to eradicate HP H5N1 globally and to
explain why H5N1 does not transmit efficiently in humans while an H1N1 pandemic virus of
swine origin spread globally in months are key examples that emphasize the critical need to
bridge these knowledge gaps. Future directions in influenza research that will help us resolve
each of the above-mentioned knowledge gaps include complete genomic and proteomic
analysis of both the virus and the host with the prospect of designing new control strategies
and the development of genetically resistant hosts.
