Catching the Flu in the Act: Quantifying influenza A virus assembly and organization using multispectral viral strains

Michael Vahey, Postdoc, Dept. Bioengineering, UC Berkeley

Friday, February 24, 2017, 3:30–4:30pm

Rm. 100 (Spanos Auditorium), Cummings Hall

Enveloped viruses have substantial impact on human health, but their mechanisms of assembly remain largely mysterious. This is particularly true of influenza A virus (IAV), which (unlike viral capsids with stereotyped shape and composition) forms heterogeneous particles whose assembly cannot be described in terms of equilibrium thermodynamics. Although the ability to assemble into particles with diverse size and composition could have important implications for infectivity, understanding how virion-to-virion differences arise and how they ultimately influence virus replication has proven challenging due to the lack of available tools for studying the assembly process. To address this challenge and establish a dynamic picture of how IAV assembles, we have engineered viral strains that harbor small fluorescent tags on each of the virus’s five major structural proteins. Unlike fluorescent proteins (e.g. GFP) that are lethal to the virus when fused to its structural proteins, these small tags are non-disruptive and allow us to quantify the protein composition and dynamics of virions as they assemble in live infected cells. These previously inaccessible measurements reveal subpopulations of virus that favor either binding to host cells or destruction of host cell receptors. The size of these different subpopulations is malleable, shifting in response to environmental stimuli, including antiviral drugs that block receptor-destruction. This phenotypic diversity could act as an evolutionary hedge, enhancing the virus’s ability to replicate in complex and unpredictable environments like the human respiratory tract.

About the Speaker

Dr. Vahey is a postdoctoral researcher in the Department of Bioengineering at UC Berkeley and a Burroughs Wellcome Fund CASI Fellow. Prior to his time at UC Berkeley, Dr. Vahey completed his PhD in the department of Electrical Engineering and Computer Science at MIT. Dr. Vahey’s research focuses on understanding how biological systems cope with external constraints, a question that he works to address by developing new biochemical and microfluidic technologies.

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