CCR5-and CXCR4-tropic HIV-1 are equally cytopathic for their T-cell targets in human lymphoid tissue

Jean Charles Grivel, Leonid B. Margolis

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)344-346
Number of pages3
JournalNature Medicine
Volume5
Issue number3
DOIs
Publication statusPublished - 22 Mar 1999

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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