Toohey K, Wehrly K, Nishio J, Perryman S, Chesebro B
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.
Virology. 1995 Oct 20;213(1):70-9. doi: 10.1006/viro.1995.1547.
The V3 hypervariable region of the HIV-1 envelope protein is a major determinant of viral tropism for macrophages. However, the replication of macrophage-tropic HIV-1 strains varies considerably in macrophages, and this variability has been linked to the V1 and V2 envelope regions. In the present study, recombinant HIV clones were generated by inserting V1 and V2 sequences from the Ba-L HIV isolate, which has a high macrophage replication level, into the genomic background of a macrophage-tropic clone with a low macrophage replication level. Infection of macrophages with varying multiplicities of infection and direct detection of the number of infected macrophages per culture showed that the Ba-L V1 and V2 envelope sequences enhanced the ability of virus to spread in the cultures. In contrast, macrophage-tropic clones with low replication efficiency infected macrophages initially but showed no evidence of spread to additional cells during the culture period. This effect on virus spread appeared to be macrophage-specific as it was not observed in cultures of T lymphocytes. Comparison of recombinant clones containing V1, V2, and V3 envelope sequences from high-efficiency Ba-L and JR-FL strains indicated that markedly different V1 and V2 sequences could impart the same rapidly spreading phenotype in macrophages.
HIV-1包膜蛋白的V3高变区是病毒对巨噬细胞嗜性的主要决定因素。然而，巨噬细胞嗜性HIV-1毒株在巨噬细胞中的复制差异很大，这种变异性与V1和V2包膜区有关。在本研究中，通过将来自巨噬细胞复制水平高的Ba-L HIV分离株的V1和V2序列插入到巨噬细胞复制水平低的巨噬细胞嗜性克隆的基因组背景中，产生了重组HIV克隆。用不同感染复数感染巨噬细胞并直接检测每个培养物中被感染巨噬细胞的数量，结果表明Ba-L V1和V2包膜序列增强了病毒在培养物中的传播能力。相比之下，复制效率低的巨噬细胞嗜性克隆最初感染巨噬细胞，但在培养期间没有显示出传播到其他细胞的迹象。这种对病毒传播的影响似乎是巨噬细胞特异性的，因为在T淋巴细胞培养物中未观察到。对含有来自高效Ba-L和JR-FL毒株的V1、V2和V3包膜序列的重组克隆进行比较表明，明显不同的V1和V2序列可在巨噬细胞中赋予相同的快速传播表型。
