Avian-type receptor-binding ability can increase influenza virus pathogenicity in macaques

Area of Science:

• Virology
• Pathogenesis
• Molecular Biology

Background:

• The 2009 H1N1 influenza pandemic was caused by novel viruses.
• A specific mutation in hemagglutinin (HA-222) influences H1N1's severity in humans.
• This mutation affects binding to human versus avian receptors.

Purpose of the Study:

• To investigate if binding to avian-type receptors increases influenza virus pathogenicity.
• To understand the role of HA-222 variants in H1N1 infection and severity.

Main Methods:

• Testing 2009 pandemic H1N1 viruses with HA-222G (severe cases) and HA-222D mutations.
• Utilizing glycan arrays to analyze receptor-binding specificity.
• Infection studies in human lung tissue and a nonhuman primate model.

Main Results:

• Viruses with HA-222D bound to human-type receptors; HA-222G viruses bound to both human and avian receptors.
• HA-222G viruses showed more efficient infection in human lung tissue, particularly alveolar type II pneumocytes.
• One H1N1 virus with HA-222G caused more severe lung damage in nonhuman primates compared to HA-222D.

Conclusions:

• Avian-type receptor binding specificity can enhance H1N1 infection of human lung cells.
• This enhanced binding may lead to more severe lung damage, increasing pathogenicity.
• Suggests a novel mechanism for increased influenza virus virulence in mammals.