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Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir Resistance

Year: 2010

Type: article

Abstract: The His274-->Tyr274 (H274Y) mutation confers oseltamivir resistance on N1 influenza neuraminidase but had long been thought to compromise viral fitness. However, beginning in 2007-2008, viruses containing H274Y rapidly became predominant among human seasonal H1N1 isolates. We show that H274Y decreases the amount of neuraminidase that reaches the cell surface and that this defect can be counteracted by secondary mutations that also restore viral fitness. Two such mutations occurred in seasonal H1N1 shortly before the widespread appearance of H274Y. The evolution of oseltamivir resistance was therefore enabled by "permissive" mutations that allowed the virus to tolerate subsequent occurrences of H274Y. An understanding of this process may provide a basis for predicting the evolution of oseltamivir resistance in other influenza strains.

Source: Science

DOI: 10.1126/science.1187816

Authors: Jesse D. Bloom, Lizhi Ian Gong, David Baltimore

Institution: California Institute of Technology

Language: English

Topic: Influenza Virus Research Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute