Hemagglutinin Subtype Specificity and Mechanisms of Highly Pathogenic Avian Influenza Virus Genesis

• Published in: Viruses Vol. 14; no. 7; p. 1566
• Main Authors: de Bruin, Anja C. M., Funk, Mathis, Spronken, Monique I., Gultyaev, Alexander P., Fouchier, Ron A. M., Richard, Mathilde
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.07.2022; MDPI
• Subjects: Amino acids; Analysis; Animals; Avian flu; avian influenza; Avian influenza viruses; Chickens; Classification; Distribution; Epidemics; Epidemiology; Genetic aspects; glycoproteins; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinins; Highly Pathogenic Avian Influenza Viruses; Identification and classification; Immunization; Infections; Influenza A virus; Influenza A virus - genetics; Influenza in Birds; Low-Pathogenic Avian Influenza Viruses; Mortality; multibasic cleavage site; pathogen evolution; Poultry; proteinases; proteolytic cleavage; Review; Viral proteins; Virulence; Virulence (Microbiology); Viruses; Waterfowl; Netherlands; Pakistan; United Kingdom > UK; Hong Kong; United States > US; China; England; Italy; Scotland; Mexico; Australia; Highly Pathogenic Avian Influenza Viruses; virulence; RNA-dependent RNA polymerase; pathogen evolution; multibasic cleavage site; proteolytic cleavage; Low-Pathogenic Avian Influenza Viruses
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14071566

Highly Pathogenic Avian Influenza Viruses (HPAIVs) arise from low pathogenic precursors following spillover from wild waterfowl into poultry populations. The main virulence determinant of HPAIVs is the presence of a multi-basic cleavage site (MBCS) in the hemagglutinin (HA) glycoprotein. The MBCS allows for HA cleavage and, consequently, activation by ubiquitous proteases, which results in systemic dissemination in terrestrial poultry. Since 1959, 51 independent MBCS acquisition events have been documented, virtually all in HA from the H5 and H7 subtypes. In the present article, data from natural LPAIV to HPAIV conversions and experimental in vitro and in vivo studies were reviewed in order to compile recent advances in understanding HA cleavage efficiency, protease usage, and MBCS acquisition mechanisms. Finally, recent hypotheses that might explain the unique predisposition of the H5 and H7 HA sequences to obtain an MBCS in nature are discussed.