Grivel J C, Margolis L B
Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Med. 1999 Mar;5(3):344-6. doi: 10.1038/6565.
A rapid decline in T-cell counts and the progression to AIDS is often associated with a switch from CCR5-tropic (R5) HIV-1 to CXCR4-tropic (X4) HIV-1 or R5/X4 HIV-1 variants. Experimental infection with R5 HIV-1 causes less T-cell depletion than infection with X4 or R5/X4 variants in T-cell cultures, in ex vivo infected human lymphoid tissue and in SCID/hu mice, despite similar replication levels. Experimental genetic changes in those sequences in gp120 that transform R5 HIV-1 variants into otherwise isogenic X4 viruses make them highly cytopathic. Thus, it is now believed that R5 variants are less cytopathic for T cells than are X4 variants. However, it is not known why CCR5-mediated HIV-1 infection does not lead to a massive CD4+ T-cell depletion, as occurs in CXCR4-mediated HIV-1 infection. Here we demonstrate that R5 HIV-1 isolates are indeed highly cytopathic, but only for CCR5+/CD4+ T cells. Because these cells constitute only a small fraction of CD4+ T cells, their depletion does not substantially change the total CD4+ T-cell count. These results may explain why the clinical stage of HIV disease correlates with viral tropism.
T细胞计数的迅速下降以及向艾滋病的进展通常与从CCR5嗜性（R5）HIV-1向CXCR4嗜性（X4）HIV-1或R5/X4 HIV-1变体的转变有关。在T细胞培养物、体外感染的人淋巴组织和SCID/hu小鼠中，R5 HIV-1的实验性感染比X4或R5/X4变体的感染导致的T细胞耗竭更少，尽管复制水平相似。gp120中那些将R5 HIV-1变体转化为其他同基因X4病毒的序列发生实验性基因变化后，会使其具有高度细胞病变性。因此，现在人们认为R5变体对T细胞的细胞病变性比X4变体小。然而，尚不清楚为什么CCR5介导的HIV-1感染不会像CXCR4介导的HIV-1感染那样导致大量CD4+ T细胞耗竭。在这里，我们证明R5 HIV-1分离株确实具有高度细胞病变性，但仅对CCR5+/CD4+ T细胞具有细胞病变性。由于这些细胞仅占CD4+ T细胞的一小部分，它们的耗竭不会显著改变总CD4+ T细胞计数。这些结果可能解释了为什么HIV疾病的临床阶段与病毒嗜性相关。
