Vpx is required for dissemination and pathogenesis of SIVSM PBj:: Evidence of macrophage-dependent viral amplification
Vpx is required for dissemination and pathogenesis of SIVSM PBj:: Evidence of macrophage-dependent viral amplification
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DOI：
10.1038/3992
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发表时间：
1998-12-01
期刊：
影响因子：
82.9
通讯作者：
Stevenson, M
中科院分区：
文献类型：
--
作者：
Hirsch, VM;Sharkey, ME;Stevenson, M
病毒辅助蛋白Vpx是猴免疫缺陷病毒（SIVSM）体外感染巨噬细胞所必需的。为了评估Vpx和巨噬细胞感染在体内的作用，我们用分子克隆的、嗜巨噬细胞的、急性致病性病毒SIVSM PBj 6.6或该病毒的辅助基因缺失突变体（Δ Vpr或Δ Vpx）静脉内或直肠内接种猪尾猕猴。野生型和SIVSM PBj Delta Vpx病毒都容易通过直肠粘膜传播。观察到野生型病毒感染和传播的局部扩增的后续“逐步”过程，但SIVSM PBj Delta Vpx未观察到，其复制的整体动力学和程度也显示出相当大的损害。在用等量的野生型和SIVSM Pbj Δ Vpx静脉内或直肠内共接种的动物中，Δ Vpx突变体处于强烈的竞争劣势。可能通过巨噬细胞依赖性机制，在初始感染的局部部位的Vpx依赖性病毒扩增可能是通过粘膜或静脉途径暴露后感染和致病后果有效传播的先决条件。
The viral accessory protein Vpx is required for productive in vitro infection of macrophages by simian immunodeficiency virus from sooty mangabey monkeys (SIVSM). To evaluate the roles of Vpx and macrophage infection in vivo, we inoculated pigtailed macaques intravenously or intrarectally with the molecularly cloned, macrophage tropic, acutely pathogenic virus SIVSM PBj 6.6, or accessory gene deletion mutants (Delta Vpr or Delta Vpx) of this virus. Both wild-type and SIVSM PBj Delta Vpx viruses were readily transmitted across the rectal mucosa. A subsequent 'stepwise' process of local amplification of infection and dissemination was observed for wild-type virus, but not for SIVSM PBj Delta Vpx, which also showed considerable impairment of the overall kinetics and extent of its replication. In animals co-inoculated with equivalent amounts of wild-type and SIVSM Pbj Delta Vpx intravenously ol intrarectally, the Delta Vpx mutant was at a strong competitive disadvantage. Vpx-dependent viral amplification at local sites of initial infection, perhaps through a macrophage-dependent mechanism, may be a prerequisite for efficient dissemination of infection and pathogenic consequences after exposure through either mucosal or intravenous routes.