Paediatric non-progression following grandmother-to-child HIV transmission.
Paediatric non-progression following grandmother-to-child HIV transmission.
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DOI：
10.1186/s12977-016-0300-y
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发表时间：
2016-09-08
期刊：
影响因子：
3.3
通讯作者：
Goulder PJ
中科院分区：
文献类型：
--
作者：
Tsai MH;Muenchhoff M;Adland E;Carlqvist A;Roider J;Cole DK;Sewell AK;Carlson J;Ndung'u T;Goulder PJ
与成人艾滋病毒感染不同，在成人艾滋病毒感染中，缓慢的疾病进展与由保护性的人类白细胞抗原I类分子(如HLA-B*81：01)介导的对艾滋病毒的免疫控制密切相关，而少数艾滋病毒感染儿童维持正常的CD4计数并保持临床健康的机制似乎不依赖于人类白细胞抗原I类，并且在很大程度上是未知的。为了更好地理解这些机制，我们在这里研究了一名感染艾滋病毒的南非女性，她在整个童年时期都没有进步。对感染艾滋病毒的家庭成员的病毒序列进行的系统发育分析，以及大母亲哺乳的历史表明，非进展性儿童是通过祖母对儿童的传播感染的。虽然祖母和孙女都表达了人类白细胞抗原B*81：01，但每个受试者的自体病毒都在免疫优势的人类白细胞抗原B*81：01限制性的Gag特异性表位TL9(TPQDLNTML，Gag 180-188)内编码了一个逃逸突变L188F。由于传播的病毒可以影响儿童和成人HIV疾病的进展，我们调查了L188F突变对复制能力的影响。当这个变种在体外被引入三个不同的HIV克隆时，病毒的复制能力完全被取消。然而，使用非进展型儿童的Gag序列构建的病毒复制效率与野生型病毒一样高。这些发现提示了另一种事件序列：没有补偿的低适合度L188F传递给两个孩子，可能导致两者进展缓慢，这与之前的研究一致，该研究表明，儿童的疾病进展可以受到传播的病毒复制能力的影响；或者传播完全补偿的病毒，以及进展缓慢，主要是由于尚未确定的HLA非依赖宿主特异性因素的结果。本文的在线版本(doi：10.1186/s12977-0160300-y)包含补充材料，授权用户可以使用。
In contrast to adult HIV infection, where slow disease progression is strongly linked to immune control of HIV mediated by protective HLA class I molecules such as HLA-B*81:01, the mechanisms by which a minority of HIV-infected children maintain normal-for-age CD4 counts and remain clinically healthy appear to be HLA class I-independent and are largely unknown. To better understand these mechanisms, we here studied a HIV-infected South African female, who remained a non-progressor throughout childhood. Phylogenetic analysis of viral sequences in the HIV-infected family members, together with the history of grand-maternal breast-feeding, indicated that, unusually, the non-progressor child had been infected via grandmother-to-child transmission. Although HLA-B*81:01 was expressed by both grandmother and grand-daughter, autologous virus in each subject encoded an escape mutation L188F within the immunodominant HLA-B*81:01-restricted Gag-specific epitope TL9 (TPQDLNTML, Gag 180–188). Since the transmitted virus can influence paediatric and adult HIV disease progression, we investigated the impact of the L188F mutant on replicative capacity. When this variant was introduced into three distinct HIV clones in vitro, viral replicative capacity was abrogated altogether. However, a virus constructed using the gag sequence of the non-progressor child replicated as efficiently as wildtype virus. These findings suggest alternative sequences of events: the transmission of the uncompensated low fitness L188F to both children, potentially contributing to slow progression in both, consistent with previous studies indicating that disease progression in children can be influenced by the replicative capacity of the transmitted virus; or the transmission of fully compensated virus, and slow progression here principally the result of HLA-independent host-specific factors, yet to be defined. The online version of this article (doi:10.1186/s12977-016-0300-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1126/science.1254031
发表时间：
2014-07-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carlson JM;Schaefer M;Monaco DC;Batorsky R;Claiborne DT;Prince J;Deymier MJ;Ende ZS;Klatt NR;DeZiel CE;Lin TH;Peng J;Seese AM;Shapiro R;Frater J;Ndung'u T;Tang J;Goepfert P;Gilmour J;Price MA;Kilembe W;Heckerman D;Goulder PJ;Allen TM;Allen S;Hunter E
通讯作者：
Hunter E
CTL逃生变体的传播和积累驱动HIV多态性与HLA之间的负相关。
影响因子：
15.3
作者：
Leslie, A;Kavanagh, D;Honeyborne, I;Pfafferott, K;Edwards, C;Pillay, T;Hilton, L;Thobakgale, C;Ramduth, D;Draenert, R;Le Gall, S;Luzzi, G;Edwards, A;Brander, C;Sewell, AK;Moore, S;Mullins, J;Moore, C;Mallal, S;Bhardwaj, N;Yusim, K;Phillips, R;Klenerman, P;Korber, B;Kiepiela, P;Walker, B;Goulder, P
通讯作者：
Goulder, P
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.4
作者：
Brockman, Mark A.;Schneidewind, Arne;Allen, Todd M.
通讯作者：
Allen, Todd M.
影响因子：
64.8
作者：
Goulder, PJR;Brander, C;Walker, BD
通讯作者：
Walker, BD