Inactivation of inhibitors by the receptor-destroying enzyme of influenza C virus

This study investigated whether influenza C virus's receptor-destroying enzyme (acetylesterase) inactivates natural inhibitors that block viral infection. Researchers tested three inhibitors—rat serum, bovine submaxillary mucin, and bovine brain gangliosides—using hemagglutination and cell infection assays. Results showed that while the acetylesterase could inactivate inhibitors at low concentrations in hemagglutination assays, approximately 100-fold higher inhibitor concentrations were required to prevent actual virus infection. Importantly, the enzyme could not inactivate these higher concentrations. The authors conclude the receptor-destroying enzyme's primary function is not to neutralize soluble inhibitors in natural infections. Supporting evidence comes from other sialic acid-binding viruses (polyomavirus, rotavirus, reovirus) that successfully infect hosts despite lacking receptor-destroying enzymes. The authors propose that the enzyme's actual role in enveloped viruses is maintaining a clean viral surface by removing sialic acid receptors from viral glycoproteins, preventing particle aggregation during maturation and entry, rather than clearing external inhibitors from infection sites.

Key findings

• Influenza C virus's acetylesterase inactivates inhibitors at concentrations roughly 100-fold lower than those required to prevent viral infection
• The receptor-destroying enzyme cannot inactivate inhibitor concentrations sufficient to block cell infection, arguing against a natural antiviral inhibitor-neutralizing role
• Several sialic acid-binding viruses lacking receptor-destroying enzymes successfully infect hosts, indicating these enzymes are not essential for overcoming soluble inhibitors
• The receptor-destroying enzyme's primary function is likely maintaining viral surface integrity in enveloped viruses, not neutralizing extracellular inhibitors during natural infection