CD4+ lymphocytopenia in acute infection of Asian macaques by a vaginally transmissible subtype-C, CCR5-tropic simian/human immunodeficiency virus (SHIV)
CD4+ lymphocytopenia in acute infection of Asian macaques by a vaginally transmissible subtype-C, CCR5-tropic simian/human immunodeficiency virus (SHIV)
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DOI：
10.1097/01.qa1.0000017963.22053.47
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发表时间：
2002-06-01
期刊：
影响因子：
--
通讯作者：
Ho, DD
中科院分区：
文献类型：
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作者：
Chen, ZW;Zhao, XQ;Ho, DD
先前使用初级HIV-1亚型C包膜产生R5嗜性SHIVCHN 19 P4。我们进一步的特点，这SHIV在两种猕猴。为了确定该分离株是否可经阴道传播，通过阴道途径向雌性猪尾猕猴接种2 × 10（3）TCID 50的SHIVCHN 19 P4。动物感染了高峰血浆病毒血症（> 10（7）病毒拷贝/mL）和快速血清转化。病毒血症伴随肠道固有层淋巴细胞（LPL）群体中的CD 4+淋巴细胞减少。在外周血和结肠淋巴结中未观察到相当的CD 4 + T细胞损失。这些研究结果表明，一种独特的R5嗜性SHIV可用于研究最流行的HIV-1亚型阴道传播中的阴道相关问题。我们还发现，静脉接种1 × 10（3）TCID 50的SHIVCHN 19 P4的恒河猴被感染，并显示肠道LPL群体中的CD 4（+）淋巴细胞减少。尽管SHIVCHN 19 P4中的vpu基因失活，但该病毒似乎在感染的初始阶段主要靶向肠道相关淋巴组织，如对另一种R5嗜性（亚型B）重组病毒SHIVSF 162 P所述。我们的数据表明，肠道中R5介导的CD 4（+）淋巴细胞减少可能与HIV-1基因型和病毒感染急性期vpu的功能无关。
An R5-tropic SHIVCHN19P4 was previously generated using a primary HIV-1 subtype-C envelope. We have further characterized this SHIV in two species of macaques. To determine whether this isolate is transmissible vaginally, female pig-tailed macaques were inoculated with 2 x 10(3) TCID50 Of SHIVCHN19P4 by the vaginal route. Animals became infected with a high peak plasma viremia (> 10(7) viral copies/mL) and rapid seroconversion. The viremia was accompanied by CD4+ lymphocytopenia in the gut lamina propria lymphocyte (LPL) Population. Comparable CD4+ T-cell loss was not seen in peripheral blood and colonic lymph nodes. These findings demonstrate a unique R5-tropic SHIV that can be used to study envelope-related issues in vaginal transmission of the most prevalent subtype of HIV-1. We also found that rhesus macaques intravenously inoculated with 1 X 10(3) TCID50 of SHIVCHN19P4 became infected and showed CD4(+) lymphocytopenia in the gut LPL Population. Despite inactivation of the vpu gene in SHIVCHN19P4, the virus appears to target mainly gut-associated lymphoid tissues during the initial stage of infection as has been described for SHIVSF162P, another R5-tropic (Subtype B) recombinant virus. Our data indicate that the R5-mediated CD4(+) lymphocytopenia in the gut is likely independent of HIV-1 genotypes and of the function of vpu at the acute phase of viral infection.