caa a22 4500 528785575 20190908091347.0 cr unu---uuuuu 180924e201509 xx s 000 0 eng 10.3929/ethz-b-000111475 doi 10.7554/eLife.07361 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/111475 Koelle Katia The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans [Elektronische Daten] [Katia Koelle, David A. Rasmussen] Open access ethresearch 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Rasmussen David A. joint author eLife Cambridge : eLife Sciences Publications 4, p. e07361 2050-084X http://hdl.handle.net/20.500.11850/111475 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/111475 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 100 1- Koelle Katia ETHRESEARCH 700 1- Rasmussen David A. joint author ETHRESEARCH 773 0- eLife Cambridge : eLife Sciences Publications 4, p. e07361 2050-084X BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access