title: Experimentally guided models reveal replication principles that shape the mutation distribution of RNA viruses.
abstract: Life history theory posits that the sequence and timing of events in an organism's lifespan are fine-tuned by evolution to maximize the production of viable offspring. In a virus, a life history strategy is largely manifested in its replication mode. Here, we develop a stochastic mathematical model to infer the replication mode shaping the structure and mutation distribution of a poliovirus population in an intact single infected cell. We measure production of RNA and poliovirus particles through the infection cycle, and use these data to infer the parameters of our model. We find that on average the viral progeny produced from each cell are approximately five generations removed from the infecting virus. Multiple generations within a single cell infection provide opportunities for significant accumulation of mutations per viral genome and for intracellular selection.
authors: Tetrad Graduate Program, University of California, San Francisco, San Francisco, United States.
authors: Michael B
authors: MB
authors: Schulte
authors: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors: Jeremy A
authors: JA
authors: Draghi
authors: Department of Biology, University of Pennsylvania, Philadelphia, United States.
authors: Joshua B
authors: JB
authors: Plotkin
authors: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States.
authors: Raul
authors: R
authors: Andino
mesh_terms: D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D017955:Poliovirus / Q000235:genetics / Q000502:physiology; D012328:RNA Viruses / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
keywords: RNA replication; evolutionary biology; genomics; infectious disease; microbiology; population structure; stochastic mathematical modeling; virus replication; viruses
references: J Virol. 2009 Dec;83(23):12579-89
references: 19776117
references: J Virol. 2014 Jun;88(11):6205-12
references: 24648454
references: Nature. 2010 Jan 21;463(7279):353-5
references: 20090752
references: Proc Biol Sci. 2010 Mar 7;277(1682):809-17
references: 19906671
references: Cell. 2010 May 28;141(5):799-811
references: 20510927
references: Trends Ecol Evol. 2010 Jul;25(7):410-8
references: 20488578
references: Infect Genet Evol. 2010 Aug;10(6):826-33
references: 19879976
references: Cell Host Microbe. 2010 Jul 22;8(1):77-85
references: 20638644
references: J Virol. 2010 Oct;84(19):9733-48
references: 20660197
references: PLoS Pathog. 2010;6(8):e1001066
references: 20865167
references: Nature. 2011 Jun 2;474(7349):92-5
references: 21637259
references: Genetics. 2011 Jul;188(3):637-46
references: 21515574
references: Cell Host Microbe. 2012 Nov 15;12(5):623-32
references: 23159052
references: Curr Protoc Microbiol. 2013;Chapter 15:Unit 15H.2
references: 23686829
references: Nature. 2014 Jan 30;505(7485):686-90
references: 24284629
references: J Virol. 2000 Mar;74(5):2219-26
references: 10666252
references: J Virol. 2000 Jul;74(14):6570-80
references: 10864671
references: Evolution. 2000 Apr;54(2):686-91
references: 10937243
references: Mol Cell. 2001 Mar;7(3):581-91
references: 11463383
references: J Virol. 2002 Apr;76(7):3276-81
references: 11884552
references: J Theor Biol. 2002 Oct 7;218(3):309-21
references: 12381432
references: J Evol Biol. 2003 Jan;16(1):64-73
references: 14635881
references: Virology. 1966 Jun;29(2):179-89
references: 4287327
references: EMBO J. 1990 Jun;9(6):2011-6
references: 2161336
references: Virology. 1992 Jun;188(2):676-84
references: 1316678
references: Proc Natl Acad Sci U S A. 1993 May 1;90(9):4171-5
references: 8387212
references: Genes Dev. 1994 Jul 15;8(14):1726-37
references: 7958852
references: J Virol. 1995 Jan;69(1):13-22
references: 7983702
references: J Virol. 1996 Oct;70(10):6576-88
references: 8794292
references: Adv Virus Res. 1996;46:1-68
references: 8824697
references: Genes Dev. 1998 Aug 1;12(15):2293-304
references: 9694795
references: J Virol. 1998 Nov;72(11):8578-85
references: 9765396
references: J Virol. 1999 Jan;73(1):427-35
references: 9847348
references: Nature. 1999 Apr 1;398(6726):441-3
references: 10201376
references: Cold Spring Harb Symp Quant Biol. 1951;16:463-70
references: 14942756
references: J Gen Virol. 2005 Mar;86(Pt 3):707-18
references: 15722531
references: Am Nat. 2005 Mar;165(3):364-73
references: 15729666
references: Nucleic Acids Res. 2005;33(10):3245-52
references: 15942027
references: Virology. 2006 Jan 5;344(1):9-16
references: 16364730
references: Nature. 2006 Jan 19;439(7074):344-8
references: 16327776
references: PLoS Pathog. 2005 Oct;1(2):e11
references: 16220146
references: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1760-5
references: 17264216
references: J R Soc Interface. 2009 Feb 6;6(31):187-202
references: 19205079
references: PLoS Biol. 2007 Jul;5(7):e183
references: 17622193
references: J Virol. 2009 Sep;83(18):9370-87
references: 19587035
references: Bull Math Biol. 2009 Oct;71(7):1671-92
references: 19459014
references: Bioinformatics. 2010 Jan 1;26(1):104-10
references: 19880371