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

Verfasser / Beitragende:
[Katia Koelle, David A. Rasmussen]
Ort, Verlag, Jahr:
2015
Enthalten in:
eLife, 4, p. e07361
Format:
Artikel (online)
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024 7 0 |a 10.3929/ethz-b-000111475  |2 doi 
024 7 0 |a 10.7554/eLife.07361  |2 doi 
035 |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/111475 
100 1 |a Koelle  |D Katia 
245 1 4 |a The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans  |h [Elektronische Daten]  |c [Katia Koelle, David A. Rasmussen] 
506 |a Open access  |2 ethresearch 
520 3 |a 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. 
540 |a Creative Commons Attribution 4.0 International  |u http://creativecommons.org/licenses/by/4.0  |2 ethresearch 
700 1 |a Rasmussen  |D David A.  |e joint author 
773 0 |t eLife  |d Cambridge : eLife Sciences Publications  |g 4, p. e07361  |x 2050-084X 
856 4 0 |u http://hdl.handle.net/20.500.11850/111475  |q text/html  |z WWW-Backlink auf das Repository (Open access) 
908 |D 1  |a Journal Article  |2 ethresearch 
950 |B ETHRESEARCH  |P 856  |E 40  |u http://hdl.handle.net/20.500.11850/111475  |q text/html  |z WWW-Backlink auf das Repository (Open access) 
950 |B ETHRESEARCH  |P 100  |E 1-  |a Koelle  |D Katia 
950 |B ETHRESEARCH  |P 700  |E 1-  |a Rasmussen  |D David A.  |e joint author 
950 |B ETHRESEARCH  |P 773  |E 0-  |t eLife  |d Cambridge : eLife Sciences Publications  |g 4, p. e07361  |x 2050-084X 
898 |a BK010053  |b XK010053  |c XK010000 
949 |B ETHRESEARCH  |F ETHRESEARCH  |b ETHRESEARCH  |j Journal Article  |c Open access