Lower HIV provirus levels are associated with more APOBEC3G protein in blood resting memory CD4+ T lymphocytes of controllers in vivo.
Lower HIV provirus levels are associated with more APOBEC3G protein in blood resting memory CD4+ T lymphocytes of controllers in vivo.
复制标题
DOI：
10.1371/journal.pone.0076002
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
D'Aquila RT
中科院分区：
文献类型：
--
作者：
De Pasquale M;Kourteva Y;Allos T;D'Aquila RT
在一些人类免疫缺陷病毒1型（HIV）感染的HLA B57和/或B27阳性受试者中，即使在没有抗逆转录病毒治疗（ART）的情况下，免疫缺陷也不会长期进展。这些“控制者”比“非控制者”受试者具有更少的含有HIV前病毒的外周血单核细胞，但是迄今为止的研究中没有专门检查携带潜伏前病毒的淋巴细胞。在控制者和ART抑制的非控制者之间，比较了静息记忆细胞中的前病毒水平，这些细胞可以作为血液中HIV的潜在储存库。还研究了APOBEC 3G（A3 G），一种细胞因子，如果不被HIV病毒体感染因子（Vif）拮抗，则可在多个步骤中阻断前病毒形成。HLA连锁的HIV控制与静息CD 4 + T中枢记忆（Tcm）和效应记忆（Tem）淋巴细胞中较少的前病毒和较多的A3 G蛋白相关（前病毒：Tcm p =0.01， Tem p =0.02; A3 G： Tcm p =0.02， Tem p =0.02）。 具有最高A3 G蛋白水平（>0.5 RLU/单位肌动蛋白）的静息记忆T细胞在体内具有最低水平的前病毒（<1，000拷贝DNA/百万细胞）（p = 0.03，Fisher精确检验）。 使用两种不同的实验方法，发现具有更多A3 G的Vif阳性病毒具有降低的离体病毒体感染性。这些结果提出了这样的假设，即HIV控制与增加的细胞A3 G相关，所述细胞A3 G可以被包装成Vif阳性病毒体，以将抑制前病毒形成的模式添加到先前描述的用于HIV控制的适应性免疫机制中。
Immunodeficiency does not progress for prolonged periods in some HLA B57- and/or B27-positive subjects with human immunodeficiency virus type 1 (HIV) infection, even in the absence of antiretroviral therapy (ART). These “controllers” have fewer HIV provirus-containing peripheral blood mononuclear cells than “non-controller” subjects, but lymphocytes that harbor latent proviruses were not specifically examined in studies to date. Provirus levels in resting memory cells that can serve as latent reservoirs of HIV in blood were compared here between controllers and ART-suppressed non-controllers. APOBEC3G (A3G), a cellular factor that blocks provirus formation at multiple steps if not antagonized by HIV virion infectivity factor (Vif), was also studied. HLA-linked HIV control was associated with less provirus and more A3G protein in resting CD4+ T central memory (Tcm) and effector memory (Tem) lymphocytes (provirus: p = 0.01 for Tcm and p = 0.02 for Tem; A3G: p = 0.02 for Tcm and p = 0.02 for Tem). Resting memory T cells with the highest A3G protein levels (>0.5 RLU per unit of actin) had the lowest levels of provirus (<1,000 copies of DNA per million cells) in vivo (p = 0.03, Fisher's exact test). Using two different experimental approaches, Vif-positive viruses with more A3G were found to have decreased virion infectivity ex vivo. These results raise the hypothesis that HIV control is associated with increased cellular A3G that may be packaged into Vif-positive virions to add that mode of inhibition of provirus formation to previously described adaptive immune mechanisms for HIV control.
登录
查看更多内容
影响因子：
6.4
作者：
Hunt, Peter W.;Brenchley, Jason;Deeks, Steven G.
通讯作者：
Deeks, Steven G.
影响因子：
15.9
作者：
Chen, Huabiao;Li, Chun;Lichterfeld, Mathias
通讯作者：
Lichterfeld, Mathias
影响因子：
5.4
作者：
Champiat, Stephane;Garrison, Keith E.;Nixon, Douglas F.
通讯作者：
Nixon, Douglas F.
影响因子：
3.7
作者：
Anderson, Jenny L.;Hope, Thomas J.
通讯作者：
Hope, Thomas J.
影响因子：
2.7
作者：
Gourraud, P. A.;Karaouni, A.;Barbour, J. D.
通讯作者：
Barbour, J. D.