Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs
Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs
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DOI：
10.1126/science.284.5415.816
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发表时间：
1999-04-30
期刊：
影响因子：
56.9
通讯作者：
Cheng-Mayer, C
中科院分区：
文献类型：
--
作者：
Harouse, JM;Gettie, A;Cheng-Mayer, C
用嵌合猿猴-人类免疫缺陷病毒 (SHIV) 感染猕猴，为研究包膜对 HIV-1 发病机制的影响提供了一个极好的体内模型。将致病性 CCR5 (R5) 特异性包膜病毒 SHIVSF162P 的感染与 CXCR4 (X4) 特异性 SHIVSF33A.2 的感染进行比较。尽管病毒复制水平相当，但感染 R5 和 X4 SHIV 的动物具有不同的致病结果，SHIVSF162P 导致 CD4(+) 肠道 T 细胞急剧减少，随后外周 CD4(+) T 细胞逐渐减少，而感染 SHIVSF33A.2 则导致外周 T 细胞严重损失，而肠道中不存在类似情况。这些结果表明共受体利用在病毒发病机制中发挥着关键作用，并为 HIV-1 包膜蛋白背景下的 HIV-1 疫苗和治疗剂的临床前检查提供了可靠的体内模型。
Infection of macaques with chimeric simian-human immunodeficiency virus (SHIV) provides an excellent in vivo model for examining the influence of envelope on HIV-1 pathogenesis. Infection with a pathogenic CCR5 (R5)-specific enveloped virus, SHIVSF162P, was compared with infection with the CXCR4 (X4)-specific SHIVSF33A.2. Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes, SHIVSF162P caused a dramatic loss of CD4(+) intestinal T cells followed by a gradual depletion in peripheral CD4(+) T cells, whereas infection with SHIVSF33A.2 caused a profound Loss in peripheral T cells that was not paralleled in the intestine. These results suggest a critical role of co-receptor utilization in viral pathogenesis and provide a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV-1 envelope protein.