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
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
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DOI：
10.1128/jvi.01708-08
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发表时间：
2008-12-15
影响因子：
5.4
通讯作者：
Haynes, Barton F.
中科院分区：
文献类型：
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作者：
Tomaras, Georgia D.;Yates, Nicole L.;Haynes, Barton F.
从传播到HIV-1感染细胞潜伏池的建立，存在免疫应答消灭人类免疫缺陷病毒1型（HIV-1）的机会之窗。研究对传播/创始者病毒的初始免疫应答的关键时间是HIV-1感染的日食期（从传播到血浆病毒首次出现的时间），但迄今为止，这一时期在逻辑上难以分析。为了探测HIV-1传播后立即发生的B细胞反应，我们确定了来自美国的血浆供体对自体和共有Env的特异性抗体反应，对于这些血浆供体，在急性感染中HIV-1血浆病毒载量（VL）上升之前、期间和之后的时间点，可以获得频繁的血浆样本，并且我们模拟了抗体对血浆病毒血症动力学的影响。第一个可检测的B细胞反应是在血浆病毒检测后8天以免疫复合物的形式出现，而第一个游离的血浆抗HIV-1抗体是针对gp 41的，并在血浆病毒出现后13天出现。相比之下，包膜gp 120特异性抗体被延迟额外的14天。进行最早病毒动力学的数学建模以确定抗体对体内HIV复制的影响，如通过血浆VL评估的。在模型中包括初始抗gp 41免疫球蛋白G（IgG）、IgM或两者的应答没有显著影响血浆VL的早期动力学。这些结果表明，由传播的HIV-1诱导的第一IgM和IgG抗体能够结合病毒体，但在自然感染中发生的时间和程度上对急性期病毒血症几乎没有影响。
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.