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.
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.
Tomaras
Georgia D
GD
Duke Human Vaccine Institute, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. gdt@duke.edu
Yates
Nicole L
NL
Liu
Pinghuang
P
Qin
Li
L
Fouda
Genevieve G
GG
Chavez
Leslie L
LL
Decamp
Allan C
AC
Parks
Robert J
RJ
Ashley
Vicki C
VC
Lucas
Judith T
JT
Cohen
Myron
M
Eron
Joseph
J
Hicks
Charles B
CB
Liao
Hua-Xin
HX
Self
Steven G
SG
Landucci
Gary
G
Forthal
Donald N
DN
Weinhold
Kent J
KJ
Keele
Brandon F
BF
Hahn
Beatrice H
BH
Greenberg
Michael L
ML
Morris
Lynn
L
Karim
Salim S Abdool
SS
Blattner
William A
WA
Montefiori
David C
DC
Shaw
George M
GM
Perelson
Alan S
AS
Haynes
Barton F
BF
D001402:B-Lymphocytes / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D008954:Models, Biological; D014766:Viremia / Q000276:immunology* / Q000635:transmission; D014771:Virion / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D054299:env Gene Products, Human Immunodeficiency Virus; C514787:gp41 protein, Human immunodeficiency virus 1