Origin and molecular evolution of primate lentiviruses-Genetic analysis of HIV/HTLV in Africa

阐明SIV和HIV的起源是理解HIV发病机制和艾滋病在世界范围内传播的基础。中非被认为是HIV-1的发源地，灵长类慢病毒从自然感染的猴子到人类的人畜共患传播被认为产生了HIV。本研究对喀麦隆4种家庭宠物山魈（Mandrillus sphinx）新分离到的SIV （SIVmnd98CM16、99CM31、99CM32、99CM33）进行了遗传鉴定。33只山魈中有4只的血浆中有HIV-2交叉反应抗体，其中2只也有HIV-1弱交叉反应抗体。为了确认猴子是否真的携带SIV，我们扩增并测序了整合酶（288-bp）亚基因组基因。系统发育分析显示，4个喀麦隆SIVmnd与先前报道的来自加蓬山魈的SIVmnd GB1没有聚类，而是形成了一个新的独立谱系。对分离的SIV进行全基因组测序，发现其基因组组织与HIV-2/SIVsmm相似，具有vpx和vpr。基于基因组的不同部分构建系统发育树时，既有相似之处，又有不同之处；SIVmnd98CM16明显包含三个不同的区域，形成了与SIVrcm和sivmnddgb1 /SIVsun/ sivhoest聚集的新的独立谱系。这种镶嵌结构可能是由于三种不同SIV谱系之间的重组，并提供了过去类人猿-类人猿跨物种传播的证据。

Elucidation of the origins of SIV and HIV is fundamental to the understanding of HIV pathogenesis and the worldwide spread of AIDS. Central Africa is thought to be the birth place of HIV-1, and zoonotic transmissions of primate lentiviruses from naturally infected monkeys to human were suggested to have generated HIV. In this study, the genetic characterization of newly isolated SIV, termed SIVmnd98CM16, 99CM31, 99CM32, 99CM33 from four household pet mandrills (Mandrillus sphinx) in Cameroon were examined.Plasma from four out of 33 mandrills had cross-reactive antibodies to HIV-2, and two of these four had also weakly cross-reactive antibodies to HIV-1. To confirm whether the monkeys truly carry SIV, the subgenomic pol (integrase, 288-bp) gene was amplified and sequenced. Phylogenetic analysis revealed that four Cameroonian SIVmnds did not cluster with previously reported SIVmnd GB1 from a mandrill in Gabon but formed a new independent lineage. When the full genome of the isolated SIV was sequenced, its genomic organization was found to be similar to that of HIV-2/SIVsmm possessing vpx and vpr. When phylogenetic trees were constructed based on different parts of the genome, some of them were similar but some showed patterns that were different from each other; SIVmnd98CM16 evidently comprised three different regions which formed a new independent lineage clustered with SIVrcm and with SIVmndGB1/SIVsun/SIVlhoest. This mosaic structure might be due to recombination among three different SIV lineages and provides evidence of simian-simian cross-species transmission in the past.