Viral factors in influenza pandemic risk assessment.

Lipsitch M1, Barclay W2, Raman R3, Russell CJ4, Belser JA5, Cobey S6, Kasson PM7, Lloyd-Smith JO8, Maurer-Stroh S9, Riley S10, Beauchemin CA11, Bedford T12, Friedrich TC13, Handel A14, Herfst S15, Murcia PR16, Roche B17, Wilke CO18, Russell CA19.

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Abstract

The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk.