title: Potent intratype neutralizing activity distinguishes human immunodeficiency virus type 2 (HIV-2) from HIV-1.
abstract: HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side the potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1-, 20 HIV-2-, and 11 dually HIV-1/2 (HIV-D)-seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2 isolates, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent and also broader than intratype NAc in HIV-1 plasma. This indicates that HIV-2-infected individuals display potent type-specific neutralizing antibodies, whereas such strong type-specific antibodies are absent in HIV-1 infection. Furthermore, the potency of intratype NAc was positively associated with the viral load of HIV-1 but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation dependent than in HIV-2 infection, where plasma viral loads typically are at least 10-fold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infections was, instead, of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2-infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from that of HIV-1 and that HIV-2 may display structures that favor triggering of potent neutralizing antibody responses.
authors.affiliation: Department of Laboratory Medicine Lund, Lund University, Lund, Sweden.
authors.forename: Gülsen
authors.initials: G
authors.lastname: Ozkaya Sahin
authors.forename: Birgitta
authors.initials: B
authors.lastname: Holmgren
authors.forename: Zacarias
authors.initials: Z
authors.lastname: da Silva
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.forename: Salma
authors.initials: S
authors.lastname: Nowroozalizadeh
authors.forename: Joakim
authors.initials: J
authors.lastname: Esbjörnsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Månsson
authors.forename: Sören
authors.initials: S
authors.lastname: Andersson
authors.forename: Hans
authors.initials: H
authors.lastname: Norrgren
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.forename: Marianne
authors.initials: M
authors.lastname: Jansson
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Fenyö
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006169:Guinea-Bissau; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D015498:HIV-2 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
references.citation: J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Dec 15;16(5):327-32
references.pmid: 9420309
references.citation: Virology. 1991 Nov;185(1):162-8
references.pmid: 1926772
references.citation: J Acquir Immune Defic Syndr (1988). 1993 Aug;6(8):941-8
references.pmid: 8315578
references.citation: PLoS Pathog. 2010 May 27;6(5):e1000908
references.pmid: 20523901
references.citation: J Virol. 2009 Jan;83(2):757-69
references.pmid: 18987148
references.citation: AIDS Res Hum Retroviruses. 1994 Nov;10(11):1401-8
references.pmid: 7888193
references.citation: J Virol. 2010 Feb;84(3):1439-52
references.pmid: 19939925
references.citation: PLoS Pathog. 2011 Jan 13;7(1):e1001251
references.pmid: 21249232
references.citation: J Infect Dis. 2009 Sep 15;200(6):984-90
references.pmid: 19656066
references.citation: J Virol. 2007 May;81(10):5331-8
references.pmid: 17301136
references.citation: AIDS. 2008 Jun 19;22(10):1195-202
references.pmid: 18525265
references.citation: Virology. 1993 Mar;193(1):528-30
references.pmid: 8438591
references.citation: Clin Infect Dis. 2009 Jun 1;48(11):e117-20
references.pmid: 19382874
references.citation: AIDS Res Hum Retroviruses. 2012 Jan;28(1):1-15
references.pmid: 21495876
references.citation: Mem Inst Oswaldo Cruz. 1996 Nov-Dec;91(6):745-6
references.pmid: 9283657
references.citation: Virology. 2002 Dec 5;304(1):70-80
references.pmid: 12490404
references.citation: Curr Opin Immunol. 2000 Aug;12(4):397-402
references.pmid: 10899027
references.citation: Arch Intern Med. 2000 Nov 27;160(21):3286-93
references.pmid: 11088091
references.citation: J Gen Virol. 2005 Dec;86(Pt 12):3385-3396
references.pmid: 16298986
references.citation: Nature. 2008 Oct 2;455(7213):613-9
references.pmid: 18833271
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4144-9
references.pmid: 12644702
references.citation: J Virol. 2010 Sep;84(18):9415-26
references.pmid: 20631143
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18514-9
references.pmid: 16339909
references.citation: J Virol. 2009 Jul;83(14):7337-48
references.pmid: 19439467
references.citation: Proc Natl Acad Sci U S A. 2003 May 27;100(11):6588-92
references.pmid: 12743376
references.citation: Lancet. 1989 Apr 15;1(8642):827-31
references.pmid: 2564911
references.citation: J Infect Dis. 1999 Oct;180(4):1116-21
references.pmid: 10479138
references.citation: J Virol. 1999 Mar;73(3):2343-9
references.pmid: 9971817
references.citation: APMIS. 2011 Aug;119(8):487-97
references.pmid: 21749448
references.citation: AIDS. 1990 Feb;4(2):107-12
references.pmid: 2328092
references.citation: AIDS Res Hum Retroviruses. 2002 Sep 1;18(13):957-67
references.pmid: 12230938
references.citation: Virology. 1999 Sep 30;262(2):312-20
references.pmid: 10502510
references.citation: J Virol. 2004 Apr;78(7):3279-95
references.pmid: 15016849
references.citation: J Infect Dis. 1996 Jan;173(1):245-8
references.pmid: 8537668
references.citation: J Virol. 1992 Apr;66(4):2473-83
references.pmid: 1347797
references.citation: Virology. 2010 Feb 5;397(1):7-13
references.pmid: 19962720
references.citation: AIDS. 1998 Sep 10;12(13):1707-14
references.pmid: 9764792
references.citation: Virology. 1996 Apr 1;218(1):134-40
references.pmid: 8615015
references.citation: Lancet. 1989 Apr 15;1(8642):852-3
references.pmid: 2564945
references.citation: AIDS. 1990 Apr;4(4):291-5
references.pmid: 2190603
references.citation: J Infect Dis. 1990 Sep;162(3):735-7
references.pmid: 2387997
references.citation: J Virol. 1997 Oct;71(10):7478-87
references.pmid: 9311827
references.citation: Retrovirology. 2010 Mar 22;7:23
references.pmid: 20307309
references.citation: Nature. 2003 Mar 20;422(6929):307-12
references.pmid: 12646921
references.citation: PLoS One. 2009;4(2):e4505
references.pmid: 19229336
references.citation: AIDS. 2009 Jul 31;23(12):1575-82
references.pmid: 19521234
references.citation: J Acquir Immune Defic Syndr (1988). 1992;5(3):303-7
references.pmid: 1740756
references.citation: AIDS. 2003 Dec 5;17(18):2561-9
references.pmid: 14685050
references.citation: AIDS. 2003 Feb 14;17(3):291-300
references.pmid: 12556682
references.citation: AIDS Res Hum Retroviruses. 1988 Apr;4(2):137-48
references.pmid: 3259142
references.citation: AIDS. 1988 Dec;2(6):433-6
references.pmid: 2853951
references.citation: Nature. 2006 Jun 15;441(7095):847-52
references.pmid: 16728975
references.citation: Curr HIV Res. 2010 Dec;8(8):579-86
references.pmid: 21054254
references.citation: J Virol. 2010 Feb;84(3):1631-6
references.pmid: 19923174