Influenza viruses, cell enzymes, and pathogenicity

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Proteolytic cleavage of influenza hemagglutinin (HA) is essential for virus infectivity, spread, tropism, and pathogenicity.
• The HA cleavage site structure and the specific cellular proteases involved dictate these outcomes.
• Different influenza viruses utilize distinct cleavage site motifs recognized by specific proteases.

Purpose of the Study:

• To elucidate the role of HA proteolytic cleavage in influenza virus pathogenesis.
• To differentiate the mechanisms of HA activation by various proteases.
• To explore novel disease control strategies based on virus activation conditions.

Main Methods:

• Analysis of HA cleavage site sequences in different influenza virus strains.
• Characterization of cellular and bacterial protease specificities for HA.
• Correlation of protease distribution with viral spread and pathogenicity.

Main Results:

• Avian influenza viruses with multibasic HA cleavage sites are activated by furin, leading to systemic infections.
• Mammalian and apathogenic avian influenza viruses with monobasic HA sites are activated by proteases with restricted tissue distribution, causing localized infections.
• Protease substrate specificity and enzyme distribution are critical determinants of influenza virus infection patterns.

Conclusions:

• The specificities of proteases cleaving the influenza HA influence viral pathogenicity and spread.
• Targeting these virus-host interactions, specifically protease activation, presents a potential avenue for disease control.