H5N1 Highly Pathogenic Avian Influenza Virus in Wild Birds

摘要

Avian influenza (Al) viruses are type A influenza viruses that are important avian and mammalian pathogens worldwide. In particular Al has been a significant threat to domestic poultry for over a century and has resulted in huge economic losses in thepoultry industry. Traditional Al virus classification schemes are based on two surface glycoproteins on the virus and the ability of an isolate to produce disease and death in chickens (Gallus domesticus). Based on serologic reactions with the hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins, Al viruses are classified into sixteen different HA subtypes (H 1-16) and nine different NA subtypes (N 1-9). Each virus has a single HA subtype and a single NA subtype, which can occur in apparently any combination. Viruses are further classified as high pathogenicity avian influenza (HPAI) or low pathogenic-ity avian influenza (LPAI) viruses based on the mortality that an isolate causes when inoculated intravenously into susceptible 4- to 6- weekold specific pathogen free chickens (Intravenous Pathogenicity Index (IVPI)). To date, only Al viruses of the H5 and H7 subtypes have been HPAI, however, the vast majority of H5 and H7 viruses are LPAI. The primary determinant of pathogenicity is the amino acid sequence at the cleavage site of the HA glycoprotein. The HA protein is synthesized as a single polypeptide HA_0 and must be cleaved into HA_1 and HA_2 before the virus is infectious. LPAI viruses have a single basic amino acid at the cleavage site of the HA, which is recognized and cleaved by trypsin-like proteases located in the epithelial cells of the respiratory and enteric tracts. HPAI viruses have multiple basic amino acids at the cleavage site of the HA, which is recognized and cleaved by trypsin-like proteases and by ubiquitous proteases in the furin enzyme family found in numerous cells of the body. Consequently LPAI virus replication is confined to cells of the respiratory and enteric tracts, while HPAI viruses can infect and replicate in additional cell types, tissues and organs throughout the body, including the neurons of the brain, acinar epithelium of the pancreas, and vascular endothelial cells.