The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans

Author:

Koelle Katia12,Rasmussen David A13

Affiliation:

1. Department of Biology, Duke University, Durham, United States

2. Fogarty International Center, National Institutes of Health, Bethesda, United States

3. Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, Switzerland

Abstract

Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.

Funder

James S. McDonnell Foundation (JSMF)

National Institute of General Medical Sciences (NIGMS)

U.S. Department of Homeland Security

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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