title: Lack of in vivo compartmentalization among HIV-1 infected naïve and memory CD4+ T cell subsets.
abstract: Viral compartmentalization between naïve and memory CD4(+) T cell subsets has been described, but only for individuals who were receiving antiretroviral therapy (ART). We present here an extensive analysis of the viral quasispecies residing in the naïve, central and effector memory CD4(+) T cell subsets in a number of therapy naïve individuals and representing an array of HIV-1 subtypes. We longitudinally analyzed subset-specific infection and evolution in a subtype B infected individual who switches from CCR5 to dual CCR5/CXCR4 coreceptor usage. We show that the central memory subset, the predominantly infected subset, harbors a more diverse viral population compared to the others. Through sequence analysis of the env C2V3 region we demonstrate a lack of viral compartmentalization among all subsets. Upon coreceptor switch we observe a pronounced increase in the infection level of the naïve population. Our findings emphasize the importance of all CD4(+) T cell subsets to viral evolution.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, The Netherlands.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Heeregrave
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Geels
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Elly
authors.initials: E
authors.lastname: Baan
authors.forename: David R
authors.initials: DR
authors.lastname: Ambrozak
authors.forename: Renee M
authors.initials: RM
authors.lastname: van der Sluis
authors.forename: Rune
authors.initials: R
authors.lastname: Bennemeer
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Georgios
authors.initials: G
authors.lastname: Pollakis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: William A
authors.initials: WA
authors.lastname: Paxton
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology*; D055815:Young Adult
chemical_list: D004279:DNA, Viral
references.citation: J Infect Dis. 2000 Feb;181(2):740-5
references.pmid: 10669367
references.citation: Virology. 2006 Apr 25;348(1):35-46
references.pmid: 16455126
references.citation: AIDS. 2002 Jun 14;16(9):1245-9
references.pmid: 12045489
references.citation: J Immunol. 2005 Dec 15;175(12):8415-23
references.pmid: 16339584
references.citation: AIDS. 2002 Nov 22;16(17):2337-40
references.pmid: 12441808
references.citation: J Leukoc Biol. 2006 Nov;80(5):1118-26
references.pmid: 17056765
references.citation: Virology. 2006 Feb 5;345(1):209-19
references.pmid: 16246391
references.citation: Curr Opin Immunol. 2005 Jun;17(3):326-32
references.pmid: 15886125
references.citation: J Virol. 1999 Dec;73(12):10489-502
references.pmid: 10559367
references.citation: Science. 1998 Apr 17;280(5362):427-31
references.pmid: 9545219
references.citation: AIDS. 2005 Nov 4;19(16):1739-50
references.pmid: 16227781
references.citation: AIDS Res Hum Retroviruses. 2003 Oct;19(10):847-56
references.pmid: 14585216
references.citation: J Exp Med. 2004 Nov 15;200(10):1299-314
references.pmid: 15545355
references.citation: J Virol. 1997 Sep;71(9):6348-58
references.pmid: 9261352
references.citation: Nature. 2002 May 2;417(6884):95-8
references.pmid: 11986671
references.citation: J Acquir Immune Defic Syndr. 2009 Feb 1;50(2):126-36
references.pmid: 19131897
references.citation: J Clin Invest. 2000 Dec;106(12):1569
references.pmid: 11120764
references.citation: J Virol. 2000 Nov;74(21):10229-35
references.pmid: 11024154
references.citation: J Infect Dis. 2000 Jul;182(1):112-22
references.pmid: 10882588
references.citation: J Virol. 2000 Jun;74(11):5347-51
references.pmid: 10799612
references.citation: Nat Immunol. 2000 Oct;1(4):285-9
references.pmid: 11017098
references.citation: Science. 1999 Nov 12;286(5443):1353-7
references.pmid: 10558989
references.citation: J Virol. 1992 May;66(5):3183-7
references.pmid: 1560543
references.citation: Infect Genet Evol. 2008 Mar;8(2):110-20
references.pmid: 18249158
references.citation: J Virol. 2003 Dec;77(23):12430-40
references.pmid: 14610167
references.citation: J Virol. 2004 Aug;78(15):7883-93
references.pmid: 15254161
references.citation: J Exp Med. 2004 Sep 20;200(6):749-59
references.pmid: 15365096
references.citation: Nature. 2005 Apr 28;434(7037):1093-7
references.pmid: 15793563
references.citation: Immunity. 2001 Oct;15(4):671-82
references.pmid: 11672548
references.citation: J Exp Med. 2007 Sep 3;204(9):2171-85
references.pmid: 17724130
references.citation: Clin Exp Immunol. 1999 Mar;115(3):443-50
references.pmid: 10193416
references.citation: J Virol. 2004 Feb;78(3):1160-8
references.pmid: 14722271
references.citation: J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):267-75
references.pmid: 16249699
references.citation: J Virol. 1999 Aug;73(8):6430-5
references.pmid: 10400736
references.citation: Cell. 1996 Aug 9;86(3):367-77
references.pmid: 8756719
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1269-74
references.pmid: 10655520
references.citation: J Virol. 2002 Sep;76(18):9465-73
references.pmid: 12186928
references.citation: Science. 1996 Mar 15;271(5255):1582-6
references.pmid: 8599114
references.citation: Science. 1996 Apr 26;272(5261):537-42
references.pmid: 8614801
references.citation: J Clin Microbiol. 1990 Mar;28(3):495-503
references.pmid: 1691208
references.citation: Annu Rev Immunol. 2003;21:265-304
references.pmid: 12524385
references.citation: J Virol. 2007 Jan;81(2):599-612
references.pmid: 17065209
references.citation: Mol Biol Evol. 2007 Aug;24(8):1596-9
references.pmid: 17488738
references.citation: J Virol. 2004 Mar;78(6):2841-52
references.pmid: 14990703
references.citation: J Virol. 2007 Aug;81(15):8165-79
references.pmid: 17507486
references.citation: PLoS Comput Biol. 2007 Feb 16;3(2):e29
references.pmid: 17305421
references.citation: J Infect Dis. 1999 Oct;180(4):1106-15
references.pmid: 10479137
references.citation: J Infect Dis. 1996 Feb;173(2):349-54
references.pmid: 8568295
references.citation: J Virol. 2008 Sep;82(18):9154-63
references.pmid: 18596085
references.citation: J Biol Chem. 2001 Apr 20;276(16):13433-41
references.pmid: 11278567
references.citation: J Acquir Immune Defic Syndr. 2005 Aug 15;39(5):507-18
references.pmid: 16044000
references.citation: Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1925-30
references.pmid: 9050881
references.citation: Blood. 2003 Apr 1;101(7):2711-20
references.pmid: 12433688
references.citation: Nature. 2003 Jul 3;424(6944):99-103
references.pmid: 12808466
references.citation: Clin Exp Immunol. 2001 Oct;126(1):69-75
references.pmid: 11678901
references.citation: J Virol. 2004 Jan;78(1):524-30
references.pmid: 14671134
references.citation: J Exp Med. 2003 Dec 15;198(12):1909-22
references.pmid: 14676302
references.citation: J Virol. 2000 Dec;74(23):11001-7
references.pmid: 11069995
references.citation: Nature. 2005 Apr 28;434(7037):1148-52
references.pmid: 15793562
references.citation: Nat Med. 1997 Feb;3(2):205-11
references.pmid: 9018240
references.citation: Retrovirology. 2006 Aug 17;3:52
references.pmid: 16916447