title: Viral quasispecies.
abstract: New generation sequencing is greatly expanding the capacity to examine the composition of mutant spectra of viral quasispecies in infected cells and host organisms. Here we review recent progress in the understanding of quasispecies dynamics, notably the occurrence of intra-mutant spectrum interactions, and implications of fitness landscapes for virus adaptation and de-adaptation. Complementation or interference can be established among components of the same mutant spectrum, dependent on the mutational status of the ensemble. Replicative fitness relates to an optimal mutant spectrum that provides the molecular basis for phenotypic flexibility, with implications for antiviral therapy. The biological impact of viral fitness renders particularly relevant the capacity of new generation sequencing to establish viral fitness landscapes. Progress with experimental model systems is becoming an important asset to understand virus behavior in the more complex environments faced during natural infections.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, USA. Electronic address: raul.andino@ucsf.edu.
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
mesh_terms: D000220:Adaptation, Biological; D014644:Genetic Variation; D005828:Genetics, Population; D059014:High-Throughput Nucleotide Sequencing; D009154:Mutation; D014774:Virulence; D018406:Virus Physiological Phenomena; D014779:Virus Replication; D014780:Viruses / Q000145:classification* / Q000235:genetics*
keywords: Adaptation; Evolution; Genome sequencing; Pathogenesis; Quasispecies; Virus
references.citation: Annu Rev Microbiol. 1997;51:151-78
references.pmid: 9343347
references.citation: Virology. 1996 Sep 1;223(1):113-9
references.pmid: 8806545
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4448-52
references.pmid: 15767582
references.citation: Nat Genet. 2005 Jul;37(7):701-9
references.pmid: 15965477
references.citation: J Virol. 2005 Oct;79(20):12650-7
references.pmid: 16188967
references.citation: Nature. 2006 Jan 19;439(7074):344-8
references.pmid: 16327776
references.citation: PLoS Pathog. 2005 Oct;1(2):e11
references.pmid: 16220146
references.citation: J Virol. 2007 Mar;81(5):2485-96
references.pmid: 17151104
references.citation: J Mol Biol. 2007 Jun 15;369(4):985-1000
references.pmid: 17481660
references.citation: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9457-62
references.pmid: 17517601
references.citation: Hepatology. 2007 Dec;46(6):1704-12
references.pmid: 17935229
references.citation: Nat Med. 2008 Feb;14(2):154-61
references.pmid: 18246077
references.citation: AIDS Rev. 2008 Apr-Jun;10(2):93-109
references.pmid: 18615120
references.citation: Nucleic Acids Res. 2008 Sep;36(16):e105
references.pmid: 18660515
references.citation: Nat Biotechnol. 2008 Oct;26(10):1135-45
references.pmid: 18846087
references.citation: PLoS Pathog. 2009 May;5(5):e1000412
references.pmid: 19412342
references.citation: J Virol. 2011 Apr;85(8):3780-91
references.pmid: 21289109
references.citation: J Virol. 2011 Jul;85(14):7169-76
references.pmid: 21543479
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16038-43
references.pmid: 21896755
references.citation: Semin Liver Dis. 2011 Nov;31(4):356-74
references.pmid: 22189976
references.citation: Microbiol Mol Biol Rev. 2012 Jun;76(2):159-216
references.pmid: 22688811
references.citation: Trends Microbiol. 2012 Dec;20(12):595-603
references.pmid: 22989762
references.citation: Nat Commun. 2012;3:1235
references.pmid: 23212364
references.citation: J Virol. 2013 Jul;87(13):7593-607
references.pmid: 23637397
references.citation: J Virol. 2013 Dec;87(23):12648-55
references.pmid: 24049174
references.citation: Nature. 2014 Jan 30;505(7485):686-90
references.pmid: 24284629
references.citation: J Virol. 2014 May;88(10):5803-15
references.pmid: 24623423
references.citation: Proc Natl Acad Sci U S A. 2014 May 6;111(18):6678-83
references.pmid: 24757055
references.citation: Nat Protoc. 2014 Jul;9(7):1760-9
references.pmid: 24967624
references.citation: J Virol. 2014 Aug;88(15):8656-66
references.pmid: 24850745
references.citation: Science. 2014 Sep 12;345(6202):1369-72
references.pmid: 25214632
references.citation: J Virol. 2014 Oct;88(20):12098-111
references.pmid: 25122776
references.citation: J Theor Biol. 2002 Nov 7;219(1):93-8
references.pmid: 12392978
references.citation: J Virol. 2003 Oct;77(20):10994-1005
references.pmid: 14512548
references.citation: J Virol. 2004 Apr;78(7):3319-24
references.pmid: 15016853
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8396-401
references.pmid: 15159545
references.citation: J Virol. 2004 Nov;78(21):11678-85
references.pmid: 15479809
references.citation: Naturwissenschaften. 1971 Oct;58(10):465-523
references.pmid: 4942363
references.citation: Naturwissenschaften. 1977 Nov;64(11):541-65
references.pmid: 593400
references.citation: Cell. 1978 Apr;13(4):735-44
references.pmid: 657273
references.citation: Science. 1982 Mar 26;215(4540):1577-85
references.pmid: 7041255
references.citation: Rev Infect Dis. 1984 May-Jun;6 Suppl 2:S499-504
references.pmid: 6330846
references.citation: Nature. 1989 Jul 13;340(6229):156-7
references.pmid: 2544809
references.citation: J Virol. 1990 Dec;64(12):6278-81
references.pmid: 2173792
references.citation: Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):199-203
references.pmid: 1846038
references.citation: Vaccine. 1990 Dec;8(6):605-8
references.pmid: 1708184
references.citation: J Virol. 1992 May;66(5):3225-9
references.pmid: 1313927
references.citation: J Virol. 1993 Oct;67(10):6071-9
references.pmid: 7690417
references.citation: J Virol. 1994 Jul;68(7):4295-301
references.pmid: 8207804
references.citation: J Biol Chem. 2014 Oct 24;289(43):29531-44
references.pmid: 25213864
references.citation: Elife. 2014;3. doi: 10.7554/eLife.03830
references.pmid: 25365453
references.citation: J Virol. 2000 Apr;74(8):3543-7
references.pmid: 10729128
references.citation: Science. 2000 Apr 14;288(5464):339-44
references.pmid: 10764648
references.citation: Virology. 2000 May 10;270(2):251-3
references.pmid: 10792982
references.citation: Science. 2002 Apr 12;296(5566):356-9
references.pmid: 11896235
references.citation: Nature. 2002 Jul 11;418(6894):144
references.pmid: 12110879
references.citation: J Virol. 1994 Aug;68(8):5280-3
references.pmid: 7545939
references.citation: J Virol. 1994 Dec;68(12):8089-101
references.pmid: 7966599
references.citation: J Virol. 1995 Jan;69(1):23-31
references.pmid: 7983713
references.citation: Virus Res. 1994 Dec;34(3):327-38
references.pmid: 7856318
references.citation: Arch Virol. 1995;140(2):259-71
references.pmid: 7710354
references.citation: J Virol. 2004 Dec;78(24):13512-21
references.pmid: 15564462