TY - JOUR TI - The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans AU - Koelle, Katia AU - Rasmussen, David A A2 - Traulsen, Arne VL - 4 PY - 2015 DA - 2015/09/15 SP - e07361 C1 - eLife 2015;4:e07361 DO - 10.7554/eLife.07361 UR - https://doi.org/10.7554/eLife.07361 AB - 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. KW - influenza evolution KW - deleterious mutations KW - antigenic evolution KW - phylodynamics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -