Characterization of Near Full-Length Transmitted/Founder HIV-1 Subtype D and A/D Recombinant Genomes in a Heterosexual Ugandan Population (2006-2011).
Characterization of Near Full-Length Transmitted/Founder HIV-1 Subtype D and A/D Recombinant Genomes in a Heterosexual Ugandan Population (2006-2011).
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DOI：
10.3390/v14020334
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发表时间：
2022-02-07
期刊：
影响因子：
--
通讯作者：
Kaleebu P
中科院分区：
文献类型：
--
作者：
Balinda SN;Kapaata A;Xu R;Salazar MG;Mezzell AT;Qin Q;Herard K;Dilernia D;Kamali A;Ruzagira E;Kibengo FM;Song H;Ochsenbauer C;Salazar-Gonzalez JF;Gilmour J;Hunter E;Yue L;Kaleebu P
乌干达传播的 HIV-1 变种的详细特征对于疫苗设计至关重要，但对传播的 D 亚型病毒全长毒株的研究有限。在这里，我们扩增了单个基因组并表征了病毒，其中一些病毒先前通过亚基因组聚合酶测序被归类为 D 亚型，这些病毒在 2006 年 12 月至 2011 年 6 月期间在乌干达传播。对 5' 和 3' 半基因组序列的分析显示，73% (19/26) 的感染涉及单一病毒传播，而根据随机病毒进化模型的预测，27% (7/26) 的感染涉及多种变体传播。对推断的传播/创始病毒的亚型分析显示，亚型间重组体的传播率很高（69%，20/29），主要涉及 A1/D，而纯 D 亚型变体占感染的三分之一（31%，9/29）。重组模式包括 gag/pol 区域 D 亚型占优势以及高度重组的包膜基因。信号肽-C1 区域和 gp41 跨膜结构域（Tat2/Rev2 侧翼区域）是 A1/D 重组事件的热点。对一组 14 个传播/创始分子克隆的分析显示，D 亚型病毒 (n = 3) 和亚型间嵌合重组体 (n = 11) 之间的复制能力没有差异。然而，感染高复制能力病毒的个体 CD4 T 细胞损失更快。独特的亚型间重组体的高传播率是惊人的，并强调了疫苗设计的非凡挑战，特别是高度可变和重组基因的包膜基因，其是旨在引发广泛中和抗体的合理设计的目标。
Detailed characterization of transmitted HIV-1 variants in Uganda is fundamentally important to inform vaccine design, yet studies on the transmitted full-length strains of subtype D viruses are limited. Here, we amplified single genomes and characterized viruses, some of which were previously classified as subtype D by sub-genomic pol sequencing that were transmitted in Uganda between December 2006 to June 2011. Analysis of 5′ and 3′ half genome sequences showed 73% (19/26) of infections involved single virus transmissions, whereas 27% (7/26) of infections involved multiple variant transmissions based on predictions of a model of random virus evolution. Subtype analysis of inferred transmitted/founder viruses showed a high transmission rate of inter-subtype recombinants (69%, 20/29) involving mainly A1/D, while pure subtype D variants accounted for one-third of infections (31%, 9/29). Recombination patterns included a predominance of subtype D in the gag/pol region and a highly recombinogenic envelope gene. The signal peptide-C1 region and gp41 transmembrane domain (Tat2/Rev2 flanking region) were hotspots for A1/D recombination events. Analysis of a panel of 14 transmitted/founder molecular clones showed no difference in replication capacity between subtype D viruses (n = 3) and inter-subtype mosaic recombinants (n = 11). However, individuals infected with high replication capacity viruses had a faster CD4 T cell loss. The high transmission rate of unique inter-subtype recombinants is striking and emphasizes the extraordinary challenge for vaccine design and, in particular, for the highly variable and recombinogenic envelope gene, which is targeted by rational designs aimed to elicit broadly neutralizing antibodies.
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影响因子：
14.9
作者：
Dilernia DA;Chien JT;Monaco DC;Brown MP;Ende Z;Deymier MJ;Yue L;Paxinos EE;Allen S;Tirado-Ramos A;Hunter E
通讯作者：
Hunter E
影响因子：
3.7
作者：
Deymier, Martin J.;Claiborne, Daniel T.;Ende, Zachary;Ratner, Hannah K.;Kilembe, William;Allen, Susan;Hunter, Eric
通讯作者：
Hunter, Eric
影响因子：
3.7
作者：
Asmal M;Hellmann I;Liu W;Keele BF;Perelson AS;Bhattacharya T;Gnanakaran S;Daniels M;Haynes BF;Korber BT;Hahn BH;Shaw GM;Letvin NL
通讯作者：
Letvin NL
影响因子：
6.7
作者：
Kijak GH;Sanders-Buell E;Chenine AL;Eller MA;Goonetilleke N;Thomas R;Leviyang S;Harbolick EA;Bose M;Pham P;Oropeza C;Poltavee K;O'Sullivan AM;Billings E;Merbah M;Costanzo MC;Warren JA;Slike B;Li H;Peachman KK;Fischer W;Gao F;Cicala C;Arthos J;Eller LA;O'Connell RJ;Sinei S;Maganga L;Kibuuka H;Nitayaphan S;Rao M;Marovich MA;Krebs SJ;Rolland M;Korber BT;Shaw GM;Michael NL;Robb ML;Tovanabutra S;Kim JH
通讯作者：
Kim JH
DOI：
10.1084/jem.20072457
发表时间：
2008-05-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goepfert PA;Lumm W;Farmer P;Matthews P;Prendergast A;Carlson JM;Derdeyn CA;Tang J;Kaslow RA;Bansal A;Yusim K;Heckerman D;Mulenga J;Allen S;Goulder PJ;Hunter E
通讯作者：
Hunter E