Evolution of highly pathogenic avian H5N1 influenza viruses and the emergence of dominant variants

Abstract

Highly pathogenic avian H5N1 viruses have circulated in South-east Asia for more than a decade and have now spread to more than 60 countries. The evolution of these viruses is characterized by frequent reassortment of the so-called ‘internal’ genes, creating novel genotypes. Additionally, over time, the surface glycoprotein, haemagglutinin (HA), which is the primary target of the adaptive immune response, has evolved by point mutation into 20 genetically and potentially antigenically distinct clades. To investigate the evolution of avian H5N1 influenza viruses, we undertook a high-resolution analysis of the reassortment of internal genes and evolution of HA of 651 avian H5N1 viruses from 2000 to 2008. Our analysis suggested: (i) all current H5N1 genotypes were derived from a single, clearly defined sequence of initial reassortment events; (ii) reassortment of just three of the internal genes had the most importance in avian H5N1 virus evolution; (iii) HA and the constellation of internal genes may be jointly important in the emergence of dominant variants. Further, our analysis led to the identification of evolutionarily significant molecular changes in the internal genes that may be significant for the emergence of these dominant variants.

Two novel reassortants of avian influenza A (H5N6) virus in China

“…On: Fri, 11 May 2018 14:48:59 H5N1 virus have frequently reassorted with other subtypes of avian influenza viruses circulating in poultry (Neumann et al, 2010;Zhao et al, 2008). In particular, H5N5, H5N8 and H5N2 subtypes bearing the genetic backbone of clade 2.3.4 H5N1 viruses have been identified in poultry populations (Gu et al, 2011;Zhao et al, 2012;Wu et al, 2014).…”

The Effect of the PB2 Mutation 627K on Highly Pathogenic H5N1 Avian Influenza Virus Is Dependent on the Virus Lineage

“…Descendants of these Qinghai Lake-like viruses spread into Europe and Africa, thus establishing the Eurasian-lineage Z viruses (clade 2.2) (5,(12)(13)(14)(15). Strikingly, the Qinghai Lake isolates and descendants possessed Lys at amino acid position 627 (627K) on the polymerase basic 2 (PB2) protein, a motif previously associated with adaptation to mammals (10,11,16).…”

Synergistic Effect of the PDZ and p85β-Binding Domains of the NS1 Protein on Virulence of an Avian H5N1 Influenza A Virus

“…Subgenotype Z.2 comprises viruses isolated in Thailand and Vietnam, whereas most subgenotype Z.3 viruses have been isolated in Indonesia. The three subgenotypes are characterized by phylogenetically distinguishable polymerase (PB2, PB1, and PA) genes (8). In addition, the NS1 protein of subgenotype Z.1 viruses differs by several amino acids from that of subgenotype Z.2 and Z.3 viruses (8).…”

“…Since 2003, these viruses have become enzootic in poultry populations in several parts of the world and have evolved rapidly through reassortment and point mutations (1)(2)(3)(4)(5)(6)(7)(8)(9). Recently, we carried out a comprehensive phylogenetic analysis of the genes that encode the internal proteins (i.e., the PB2, PB1, PA, NP, M, and NS genes) of HPAI H5N1 viruses isolated from 2000 to 2008 and found that viruses of the so-called genotype Z (6,10), which was first reported in 2002, have since diverged into three subgenotypes, Z.1 to Z.3 (8). Subgenotype Z.1 includes the Qinghai Lake viruses (which caused an outbreak among wild aquatic birds at Qinghai Lake, China, in 2005 [11][12][13]) and their descendants, which have spread into Europe, Africa, and the Middle East.…”