title: A multi-scale analysis of influenza A virus fitness trade-offs due to temperature-dependent virus persistence.
abstract: Successful replication within an infected host and successful transmission between hosts are key to the continued spread of most pathogens. Competing selection pressures exerted at these different scales can lead to evolutionary trade-offs between the determinants of fitness within and between hosts. Here, we examine such a trade-off in the context of influenza A viruses and the differential pressures exerted by temperature-dependent virus persistence. For a panel of avian influenza A virus strains, we find evidence for a trade-off between the persistence at high versus low temperatures. Combining a within-host model of influenza infection dynamics with a between-host transmission model, we study how such a trade-off affects virus fitness on the host population level. We show that conclusions regarding overall fitness are affected by the type of link assumed between the within- and between-host levels and the main route of transmission (direct or environmental). The relative importance of virulence and immune response mediated virus clearance are also found to influence the fitness impacts of virus persistence at low versus high temperatures. Based on our results, we predict that if transmission occurs mainly directly and scales linearly with virus load, and virulence or immune responses are negligible, the evolutionary pressure for influenza viruses to evolve toward good persistence at high within-host temperatures dominates. For all other scenarios, influenza viruses with good environmental persistence at low temperatures seem to be favored.
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, Georgia, United States of America. ahandel@uga.edu
authors.forename: Andreas
authors.initials: A
authors.lastname: Handel
authors.forename: Justin
authors.initials: J
authors.lastname: Brown
authors.forename: David
authors.initials: D
authors.lastname: Stallknecht
authors.forename: Pejman
authors.initials: P
authors.lastname: Rohani
mesh_terms: D000818:Animals; D001717:Birds; D019295:Computational Biology; D005243:Feces / Q000821:virology; D056084:Genetic Fitness / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000635:transmission / Q000821:virology; D008954:Models, Biological; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology*; D013696:Temperature
references.citation: Poult Sci. 2011 Jun;90(6):1234-8
references.pmid: 21597064
references.citation: PLoS One. 2012;7(8):e43115
references.pmid: 22952637
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17736-41
references.pmid: 19004788
references.citation: Avian Dis. 2010 Mar;54(1 Suppl):461-5
references.pmid: 20521680
references.citation: Scand J Immunol. 2004 Jan;59(1):1-15
references.pmid: 14723616
references.citation: Am Nat. 2009 Apr;173(4):446-55
references.pmid: 19231966
references.citation: Proc Biol Sci. 2008 Apr 7;275(1636):853-9
references.pmid: 18198145
references.citation: J Infect Dis. 1979 Oct;140(4):610-3
references.pmid: 512419
references.citation: J Virol. 2009 Jul;83(14):7151-65
references.pmid: 19439465
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10365-9
references.pmid: 19497868
references.citation: Infect Genet Evol. 2009 Sep;9(5):800-5
references.pmid: 19379841
references.citation: PLoS One. 2011;6(10):e26566
references.pmid: 22028909
references.citation: Annu Rev Med. 2006;57:139-54
references.pmid: 16409141
references.citation: Am Nat. 2011 Dec;178(6):E174-E188
references.pmid: 22089879
references.citation: PLoS Comput Biol. 2007 Dec;3(12):e240
references.pmid: 18069885
references.citation: Proc Biol Sci. 1996 Jun 22;263(1371):715-21
references.pmid: 8763793
references.citation: Bull Math Biol. 2008 Apr;70(3):820-67
references.pmid: 18278533
references.citation: Avian Dis. 2007 Mar;51(1 Suppl):285-9
references.pmid: 17494568
references.citation: PLoS One. 2008;3(12):e3942
references.pmid: 19079604
references.citation: J Theor Biol. 2008 Feb 7;250(3):569-79
references.pmid: 18062992
references.citation: J Theor Biol. 2004 Dec 7;231(3):435-41
references.pmid: 15501473
references.citation: Avian Dis. 1990 Apr-Jun;34(2):406-11
references.pmid: 2142420
references.citation: Trends Ecol Evol. 2008 Sep;23(9):511-7
references.pmid: 18657880
references.citation: Theor Popul Biol. 2007 Dec;72(4):576-91
references.pmid: 17900643
references.citation: J R Soc Interface. 2009 Dec 6;6 Suppl 6:S737-46
references.pmid: 19773291
references.citation: Genetics. 2008 Dec;180(4):2193-200
references.pmid: 18854584
references.citation: Vet Microbiol. 2009 Apr 14;136(1-2):20-6
references.pmid: 19081209
references.citation: Avian Dis. 1990 Apr-Jun;34(2):412-8
references.pmid: 2142421
references.citation: J R Soc Interface. 2005 Sep 22;2(4):281-93
references.pmid: 16849186
references.citation: Annu Rev Med. 2000;51:407-21
references.pmid: 10774473
references.citation: Trends Microbiol. 2011 Jan;19(1):24-32
references.pmid: 21055948
references.citation: J Infect. 2008 Nov;57(5):361-73
references.pmid: 18848358
references.citation: Nat Rev Microbiol. 2005 Aug;3(8):591-600
references.pmid: 16064053
references.citation: J R Soc Interface. 2010 Jan 6;7(42):35-47
references.pmid: 19474085
references.citation: Parasitology. 2007 Jul;134(Pt 7):949-58
references.pmid: 17324298
references.citation: Poult Sci. 1998 Jan;77(1):75-82
references.pmid: 9469755
references.citation: PLoS Comput Biol. 2010 Oct 28;6(10):e1000969
references.pmid: 21060854
references.citation: J Infect Dis. 2008 Sep 1;198(5):687-93
references.pmid: 18662132
references.citation: PLoS One. 2012;7(3):e32729
references.pmid: 22427870
references.citation: PLoS Biol. 2006 Jul;4(7):e193
references.pmid: 16756387
references.citation: PLoS Comput Biol. 2012;8(6):e1002588
references.pmid: 22761567
references.citation: Annu Rev Pathol. 2008;3:499-522
references.pmid: 18039138
references.citation: PLoS One. 2010 Jun 23;5(6):e10997
references.pmid: 20585637
references.citation: J Wildl Dis. 2011 Jul;47(3):566-78
references.pmid: 21719821
references.citation: J Wildl Dis. 2012 Oct;48(4):991-8
references.pmid: 23060500
references.citation: J Virol. 2010 Apr;84(8):3974-83
references.pmid: 20130053
references.citation: Evolution. 2011 Dec;65(12):3448-61
references.pmid: 22133217
references.citation: Science. 2011 Aug 12;333(6044):850-6
references.pmid: 21798894
references.citation: Theor Popul Biol. 2006 Sep;70(2):201-13
references.pmid: 16765401
references.citation: Biol Rev Camb Philos Soc. 2004 Nov;79(4):849-69
references.pmid: 15682873
references.citation: BMC Med. 2009 Dec 24;7:81
references.pmid: 20034378
references.citation: PLoS Pathog. 2009 May;5(5):e1000424
references.pmid: 19436701
references.citation: Indoor Air. 2009 Oct;19(5):401-13
references.pmid: 19659895
references.citation: J Virol. 2010 Jul;84(13):6687-98
references.pmid: 20410284
references.citation: J Theor Biol. 2010 Aug 21;265(4):501-10
references.pmid: 20570681
references.citation: Risk Anal. 2009 Sep;29(9):1292-303
references.pmid: 19558389
references.citation: PLoS One. 2012;7(2):e31114
references.pmid: 22348042
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2011 Jul-Aug;3(4):429-45
references.pmid: 21197654
references.citation: J Theor Biol. 2010 Jun 7;264(3):729-36
references.pmid: 20211630
references.citation: Science. 1996 Jan 5;271(5245):14-5
references.pmid: 8539587
references.citation: Bull Math Biol. 2009 May;71(4):845-62
references.pmid: 19096894
references.citation: Vet Microbiol. 2000 May 22;74(1-2):3-13
references.pmid: 10799774
references.citation: Microbiol Rev. 1992 Mar;56(1):152-79
references.pmid: 1579108
references.citation: Am J Epidemiol. 1983 Oct;118(4):573-82
references.pmid: 6637984
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14711-5
references.pmid: 19706556
references.citation: N Engl J Med. 1998 May 14;338(20):1405-12
references.pmid: 9580647
references.citation: PLoS Comput Biol. 2009 Oct;5(10):e1000536
references.pmid: 19847288
references.citation: Proc Biol Sci. 1998 Aug 22;265(1405):1545-52
references.pmid: 9744106
references.citation: N Engl J Med. 2000 Mar 30;342(13):921-9
references.pmid: 10738050
references.citation: Nat Med. 2004 Dec;10(12 Suppl):S82-7
references.pmid: 15577936
references.citation: Am J Epidemiol. 2009 Jul 15;170(2):257-65
references.pmid: 19474071
references.citation: PLoS Pathog. 2007 Oct 19;3(10):1470-6
references.pmid: 17953482
references.citation: BMC Public Health. 2011 Feb 25;11 Suppl 1:S7
references.pmid: 21356136
references.citation: J Virol. 2006 Aug;80(15):7590-9
references.pmid: 16840338
references.citation: Philos Trans R Soc Lond B Biol Sci. 2010 Jun 27;365(1548):1931-41
references.pmid: 20478888
references.citation: PLoS One. 2012;7(5):e37088
references.pmid: 22615902
references.citation: Lancet. 2003 Nov 22;362(9397):1733-45
references.pmid: 14643124
references.citation: Theor Popul Biol. 2006 Mar;69(2):145-53
references.pmid: 16198387
references.citation: JAMA. 2003 Jan 8;289(2):179-86
references.pmid: 12517228
references.citation: J Math Biol. 2010 May;60(5):711-26
references.pmid: 19633852
references.citation: J R Soc Interface. 2010 Sep 6;7(50):1311-8
references.pmid: 20335194
references.citation: PLoS Comput Biol. 2009 Apr;5(4):e1000346
references.pmid: 19360126