Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia

被引:500
作者
Tomaras, Georgia D. [1 ,3 ]
Yates, Nicole L.
Liu, Pinghuang
Qin, Li [4 ]
Fouda, Genevieve G.
Chavez, Leslie L. [5 ]
Decamp, Allan C. [4 ]
Parks, Robert J. [2 ]
Ashley, Vicki C.
Lucas, Judith T.
Cohen, Myron [6 ]
Eron, Joseph [6 ]
Hicks, Charles B. [2 ]
Liao, Hua-Xin [2 ]
Self, Steven G. [4 ]
Landucci, Gary [7 ]
Forthal, Donald N. [7 ]
Weinhold, Kent J. [3 ]
Keele, Brandon F. [8 ]
Hahn, Beatrice H. [8 ]
Greenberg, Michael L.
Morris, Lynn [9 ]
Karim, Salim S. Abdool [10 ]
Blattner, William A. [11 ]
Montefiori, David C.
Shaw, George M. [8 ]
Perelson, Alan S. [5 ]
Haynes, Barton F. [2 ,3 ]
机构
[1] Duke Univ, Dept Surg, Duke Human Vaccine Inst, Med Ctr,Sch Med, Durham, NC 27710 USA
[2] Duke Univ, Sch Med, Dept Med, Durham, NC 27710 USA
[3] Duke Univ, Sch Med, Dept Immunol, Durham, NC 27710 USA
[4] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Stat Ctr HIV AIDS Res, Seattle, WA 98104 USA
[5] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA
[6] Univ N Carolina, Chapel Hill, NC USA
[7] Univ Calif Irvine, Irvine, CA USA
[8] Univ Alabama Birmingham, Birmingham, AL USA
[9] Natl Inst Communicable Dis, Johannesburg, South Africa
[10] Univ KwaZulu Natal, Ctr AIDS Programme Res S Africa, Durban, South Africa
[11] Univ Maryland, Inst Human Virol, Div Epidemiol & Prevent, Baltimore, MD 21202 USA
关键词
D O I
10.1128/JVI.01708-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.
引用
收藏
页码:12449 / 12463
页数:15
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