Igarashi Tatsuhiko, Donau Olivia K, Imamichi Hiromi, Dumaurier Marie-Jeanne, Sadjadpour Reza, Plishka Ronald J, Buckler-White Alicia, Buckler Charles, Suffredini Anthony F, Lane H Clifford, Moore John P, Martin Malcolm A
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Virol. 2003 Dec;77(24):13042-52. doi: 10.1128/jvi.77.24.13042-13052.2003.
After the nearly complete and irreversible depletion of CD4(+) T lymphocytes induced by highly pathogenic simian/human immunodeficiency virus chimeric viruses (SHIVs) during infections of rhesus monkeys, tissue macrophages are able to sustain high levels (>10(6) viral RNA copies/ml) of plasma viremia for several months. We recently reported that the virus present in the plasma during the late macrophage phase of infection had acquired changes that specifically targeted the V2 region of gp120 (H. Imamichi et al., Proc. Natl. Acad. Sci. USA 99:13813-13818, 2002); some of these SHIV variants were macrophage-tropic (M-tropic). Those findings have been extended by examining the tropic properties, coreceptor usage, and gp120 structure of five independent SHIVs recovered directly from lymph nodes of late-stage animals. All of these tissue-derived SHIV isolates were able to infect alveolar macrophages. These M-tropic SHIVs used CXCR4, not CCR5, for infections of rhesus monkey PBMC and primary alveolar macrophages. Because the starting highly pathogenic T-tropic SHIV inoculum also utilized CXCR4, these results indicate that the acquisition of M-tropism in the SHIV-macaque system is not accompanied by a change in coreceptor usage. Compared to the initial T-tropic SHIV inoculum, tissue-derived M-tropic SHIVs from individual infected animals carry gp120s containing similar changes (specific amino acid deletions, substitutions, and loss of N-linked glycosylation sites), primarily within the V1 and/or V2 regions of gp120.
在恒河猴感染高致病性猿猴/人类免疫缺陷病毒嵌合病毒（SHIV）期间，CD4(+) T淋巴细胞几乎完全且不可逆地耗竭后，组织巨噬细胞能够使血浆病毒血症维持在高水平（>10(6) 病毒RNA拷贝/毫升）数月之久。我们最近报道，在感染后期巨噬细胞阶段血浆中存在的病毒发生了变化，这些变化专门针对gp120的V2区域（H. Imamichi等人，《美国国家科学院院刊》99:13813 - 13818，2002年）；其中一些SHIV变体具有巨噬细胞嗜性（M嗜性）。通过检查直接从晚期动物淋巴结中分离出的五种独立SHIV的嗜性特性、共受体使用情况和gp120结构，这些发现得到了扩展。所有这些源自组织的SHIV分离株都能够感染肺泡巨噬细胞。这些M嗜性SHIV在感染恒河猴外周血单核细胞（PBMC）和原代肺泡巨噬细胞时使用CXCR4而非CCR5作为共受体。由于起始的高致病性T嗜性SHIV接种物也利用CXCR4，这些结果表明，在SHIV - 猕猴系统中获得M嗜性并不伴随着共受体使用的改变。与最初的T嗜性SHIV接种物相比，来自个体感染动物的源自组织的M嗜性SHIV携带的gp120含有类似的变化（特定氨基酸缺失、替换以及N - 连接糖基化位点的丢失），主要位于gp120的V1和/或V2区域内。
