Immune Escape Adaptive Mutations in the H7N9 Avian Influenza Hemagglutinin Protein Increase Virus Replication Fitness...

Area of Science:

• Virology
• Immunology
• Public Health

Background:

• H7N9 avian influenza viruses (AIVs) pose a continuous threat to human and animal health.
• Immune escape mutants, identified through serial passaging, carry specific hemagglutinin (HA) mutations (A125T, A151T, L217Q).
• These mutations have been detected in recent field isolates, necessitating an investigation into their impact.

Purpose of the Study:

• To evaluate the impact of H7N9 HA mutations (A125T, A151T, L217Q) on virus properties.
• To assess the potential threat of these serum escape mutants to humans and poultry.
• To understand the role of N-linked glycosylation in receptor binding and viral fitness.

Main Methods:

• Serial passaging of H7N9 virus in ferret antiserum to generate immune escape mutants.
• Analysis of HA protein substitutions (A125T, A151T, L217Q).
• Investigation of receptor binding, pH of fusion, thermal stability, and virus replication in vitro and in ovo.

Main Results:

• Serum escape mutants exhibited robust replication, increased thermal stability, and a lower pH of fusion.
• Mutations A125T and A151T, via N-linked glycosylation, reduced receptor-binding avidity.
• The triple mutant (A125T+A151T+L217Q) abolished human-like receptor binding while retaining avian-like receptor binding.

Conclusions:

• H7N9 viruses with HA mutations A125T+A151T+L217Q may present a reduced pandemic risk due to altered receptor binding.
• These mutants demonstrate enhanced replication and stability, posing a heightened threat to poultry populations.
• Antigenic drift and improved viral fitness in poultry underscore the continued risk posed by these emergent H7N9 variants.