title: Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.
abstract: The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens.
authors: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. hliao@duke.edu
authors: Hua-Xin
authors: HX
authors: Liao
authors: Xi
authors: X
authors: Chen
authors: Supriya
authors: S
authors: Munshaw
authors: Ruijun
authors: R
authors: Zhang
authors: Dawn J
authors: DJ
authors: Marshall
authors: Nathan
authors: N
authors: Vandergrift
authors: John F
authors: JF
authors: Whitesides
authors: Xiaozhi
authors: X
authors: Lu
authors: Jae-Sung
authors: JS
authors: Yu
authors: Kwan-Ki
authors: KK
authors: Hwang
authors: Feng
authors: F
authors: Gao
authors: Martin
authors: M
authors: Markowitz
authors: Sonya L
authors: SL
authors: Heath
authors: Katharine J
authors: KJ
authors: Bar
authors: Paul A
authors: PA
authors: Goepfert
authors: David C
authors: DC
authors: Montefiori
authors: George C
authors: GC
authors: Shaw
authors: S Munir
authors: SM
authors: Alam
authors: David M
authors: DM
authors: Margolis
authors: Thomas N
authors: TN
authors: Denny
authors: Scott D
authors: SD
authors: Boyd
authors: Eleanor
authors: E
authors: Marshal
authors: Michael
authors: M
authors: Egholm
authors: Birgitte B
authors: BB
authors: Simen
authors: Bozena
authors: B
authors: Hanczaruk
authors: Andrew Z
authors: AZ
authors: Fire
authors: Gerald
authors: G
authors: Voss
authors: Garnett
authors: G
authors: Kelsoe
authors: Georgia D
authors: GD
authors: Tomaras
authors: M Anthony
authors: MA
authors: Moody
authors: Thomas B
authors: TB
authors: Kepler
authors: Barton F
authors: BF
authors: Haynes
mesh_terms: D000328:Adult; D019070:Cell Lineage; D005260:Female; D015483:HIV Antibodies / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D009154:Mutation; D010802:Phylogeny; D010950:Plasma Cells / Q000276:immunology / Q000821:virology; D017422:Sequence Analysis, DNA; D019562:Viral Load; D014766:Viremia / Q000276:immunology
chemical_list: D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41