The evolution of H5N1 influenza viruses in Indonesia to mammalian hosts: a review of molecular markers

The danger of a global pandemic caused by zoonotic influenza viruses is increasing as the frequency of human illnesses caused by avian and swine flu viruses rises. Global pandemic preparedness initiatives have largely concentrated on H5N1 avian influenza virus. In this review, we compile the research on H5N1 virus prevalence and risk assessment, and we augment this with an overview of recent molecular evaluations of important markers of mammalian adaptation found in haemagglutinin and polymerase proteins (PB2, PB1 and PA). There is increasing evidence that H5N1 viruses circulating among various species in Indonesia (Indonesian and Eurasian lineages) are constantly adapting, resulting in the emergence of new strains with high affinity to the α2,6 receptor and enhanced polymerase function in mammalian cells. The pandemic risk presented by this virus subtype is further exacerbated by higher prevalence rates of particular mammalian adaptation markers and the increased transmission of particular viruses in mammalian animal models.