title: Demographic processes affect HIV-1 evolution in primary infection before the onset of selective processes.
abstract: HIV-1 transmission and viral evolution in the first year of infection were studied in 11 individuals representing four transmitter-recipient pairs and three independent seroconverters. Nine of these individuals were enrolled during acute infection; all were men who have sex with men (MSM) infected with HIV-1 subtype B. A total of 475 nearly full-length HIV-1 genome sequences were generated, representing on average 10 genomes per specimen at 2 to 12 visits over the first year of infection. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled during acute HIV-1 infection. Restriction to a single founder variant was not due to a lack of diversity in the transmitter as homogeneous populations were found in recipients from transmitters with chronic infection. Mutational patterns indicative of rapid viral population growth dominated during the first 5 weeks of infection and included a slight contraction of viral genetic diversity over the first 20 to 40 days. Subsequently, selection dominated, most markedly in env and nef. Mutants were detected in the first week and became consensus as early as day 21 after the onset of symptoms of primary HIV infection. We found multiple indications of cytotoxic T lymphocyte (CTL) escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with mutually exclusive mutations nearby, indicating the existence of a maturational escape process, possibly in adaptation to viral fitness constraints or to immune responses against new variants. We showed that establishment of HIV-1 infection is likely due to a biological mechanism that restricts transmission rather than to early adaptive evolution during acute infection. Furthermore, the diversity of HIV strains coupled with complex and individual-specific patterns of CTL escape did not reveal shared sequence characteristics of acute infection that could be harnessed for vaccine design.
authors: Department of Microbiology, SC-42, University of Washington School of Medicine, Seattle, WA 98195-8070, USA.
authors: Joshua T
authors: JT
authors: Herbeck
authors: Morgane
authors: M
authors: Rolland
authors: Yi
authors: Y
authors: Liu
authors: Sherry
authors: S
authors: McLaughlin
authors: John
authors: J
authors: McNevin
authors: Hong
authors: H
authors: Zhao
authors: Kim
authors: K
authors: Wong
authors: Julia N
authors: JN
authors: Stoddard
authors: Dana
authors: D
authors: Raugi
authors: Stephanie
authors: S
authors: Sorensen
authors: Indira
authors: I
authors: Genowati
authors: Brian
authors: B
authors: Birditt
authors: Angela
authors: A
authors: McKay
authors: Kurt
authors: K
authors: Diem
authors: Brandon S
authors: BS
authors: Maust
authors: Wenjie
authors: W
authors: Deng
authors: Ann C
authors: AC
authors: Collier
authors: Joanne D
authors: JD
authors: Stekler
authors: M Juliana
authors: MJ
authors: McElrath
authors: James I
authors: JI
authors: Mullins
references: J Virol. 2008 Sep;82(17):8548-59
references: 18596105
references: Virology. 1992 Jul;189(1):103-10
references: 1376536
references: PLoS Pathog. 2009 Apr;5(4):e1000365
references: 19343217
references: J Virol. 2002 Dec;76(23):11953-9
references: 12414937
references: J Virol. 1998 Jan;72(1):617-23
references: 9420266
references: J Virol. 1998 Oct;72(10):8240-51
references: 9733867
references: Lancet. 1997 Oct 18;350(9085):1141
references: 9343504
references: Nature. 2009 Apr 2;458(7238):641-5
references: 19242411
references: J Virol. 2004 Oct;78(20):11208-18
references: 15452240
references: J Infect Dis. 2005 May 1;191(9):1403-9
references: 15809897
references: J Acquir Immune Defic Syndr (1988). 1992;5(2):143-7
references: 1732506
references: Am J Med. 1997 May 19;102(5B):117-24; discussion 125-6
references: 9845513
references: J Virol. 2010 Jun;84(12):6241-7
references: 20375173
references: J Virol. 1994 Sep;68(9):6103-10
references: 8057491
references: J Virol. 1993 Jun;67(6):3345-56
references: 8497055
references: J Virol. 2005 Nov;79(21):13239-49
references: 16227247
references: J Virol. 2006 Feb;80(4):1637-44
references: 16439520
references: PLoS Pathog. 2009 Sep;5(9):e1000590
references: 19779560
references: Protein Sci. 2003 May;12(5):1007-17
references: 12717023
references: J Infect Dis. 2000 Mar;181(3):872-80
references: 10720507
references: AIDS. 2003 Sep 5;17(13):1871-9
references: 12960819
references: J Virol. 2006 Oct;80(19):9519-29
references: 16973556
references: J Virol. 2008 Apr;82(8):3952-70
references: 18256145
references: J Virol. 1994 Oct;68(10):6672-83
references: 8084001
references: AIDS Res Hum Retroviruses. 1996 Dec 10;12(18):1681-5
references: 8959243
references: J Virol. 2009 Mar;83(6):2715-27
references: 19116249
references: Tissue Antigens. 1995 Feb;45(2):81-90
references: 7792765
references: J Virol. 2009 Feb;83(3):1228-39
references: 19019964
references: Science. 2007 Mar 16;315(5818):1583-6
references: 17363674
references: Glycobiology. 2004 Dec;14(12):1229-46
references: 15175256
references: Genetics. 1987 May;116(1):153-9
references: 3110004
references: PLoS Pathog. 2009 Apr;5(4):e1000377
references: 19360131
references: J Infect Dis. 2008 Sep 1;198(5):687-93
references: 18662132
references: J Exp Med. 2009 Jun 8;206(6):1253-72
references: 19487423
references: Tissue Antigens. 2003 Nov;62(5):378-84
references: 14617044
references: J Virol. 2005 Feb;79(3):1734-42
references: 15650198
references: J Virol. 2007 Jan;81(1):193-201
references: 17065207
references: PLoS Pathog. 2010 Aug 19;6(8):e1001053
references: 20808902
references: Bioinformatics. 1999 Feb;15(2):174-5
references: 10089204
references: Ann Intern Med. 1998 Apr 15;128(8):613-20
references: 9537934
references: Syst Biol. 2003 Oct;52(5):696-704
references: 14530136
references: J Virol. 2007 Nov;81(22):12179-88
references: 17728222
references: Science. 1996 May 24;272(5265):1167-70
references: 8638160
references: Ann Intern Med. 1995 Apr 15;122(8):573-9
references: 7887550
references: Nature. 1995 Jun 15;375(6532):606-11
references: 7791879
references: PLoS Pathog. 2009 May;5(5):e1000414
references: 19424423
references: J Virol. 2010 Nov;84(22):11937-49
references: 20810731
references: J Virol Methods. 2006 Sep;136(1-2):118-25
references: 16701907
references: J Infect Dis. 2008 Apr 1;197(7):1011-5
references: 18419538
references: PLoS Pathog. 2009 Jan;5(1):e1000274
references: 19165325
references: Nat Med. 1997 Nov;3(11):1259-65
references: 9359702
references: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552-7
references: 18490657
references: Jpn J Genet. 1994 Oct;69(5):481-8
references: 7999369
references: J Virol. 2003 Dec;77(24):13376-88
references: 14645592
references: J Virol. 1999 Dec;73(12):10489-502
references: 10559367
references: PLoS Pathog. 2007 Nov;3(11):e157
references: 18052528
references: AIDS. 2002 Jan 25;16(2):189-95
references: 11807302
references: PLoS Pathog. 2010 May 13;6(5):e1000890
references: 20485520
references: J Infect Dis. 2004 May 15;189(10):1785-92
references: 15122514
references: J Virol. 2009 Apr;83(8):3556-67
references: 19193811
references: Nat Med. 2011 Mar;17(3):366-71
references: 21358627
references: JAMA. 2007 Jun 6;297(21):2349-50
references: 17551128
references: Bioinformatics. 2005 Mar 1;21(5):676-9
references: 15509596
references: AIDS Res Hum Retroviruses. 2008 Apr;24(4):561-71
references: 18426336
references: J Exp Med. 2009 Jun 8;206(6):1273-89
references: 19487424
references: J Virol Methods. 2010 Sep;168(1-2):114-20
references: 20451557
references: AIDS Res Hum Retroviruses. 1994 Sep;10(9):1187-9
references: 7826703
references: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references: 7984417
references: Genetics. 1989 Nov;123(3):585-95
references: 2513255
references: J Virol. 1994 Jul;68(7):4650-5
references: 8207839
references: Science. 1993 Aug 27;261(5125):1179-81
references: 8356453
references: Genetics. 1991 Oct;129(2):555-62
references: 1743491
references: Genetics. 2004 Aug;167(4):1573-83
references: 15342499
references: Genetics. 1993 Mar;133(3):693-709
references: 8454210
references: J Theor Biol. 2009 Nov 21;261(2):341-60
references: 19660475