Coreceptor choice and T cell depletion by R5, X4, and R5X4 HIV-1 variants in CCR5-deficient (CCR5δ32) and normal human lymphoid tissue

Nina Malkevitch, David H. McDermott, Yanjie Yi, Jean-Charles B. Grivel, Dominique Schols, Erik De Clercq, Philip M. Murphy, Svetlana Glushakova, Ronald G. Collman, Leonid Margolis

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Coreceptor utilization by HIV-1 is an important determinant of pathogenesis. However, coreceptor selectivity is defined in vitro, while in vivo critical pathogenic events occur in lymphoid tissues. Using pharmacological inhibitors, we recently provided evidence that coreceptor selectivity by the R5X4 dual-tropic isolate 89.6 was more restricted in ex vivo infected lymphoid tissue than in vitro [S. Glushakova, Y. Yi, J. C. Grivel, A. Singh, D. Schols, E. De Clercq, R. G. Collman, and L. Margolis (1999). J. Clin. Invest. 104, R7-R11]. Here we extend those observations using CCR5-deficient (CCR5Δ32) lymphoid tissue as well as additional primary isolates. We definitively show that neither CCR5 nor secondary coreceptors used in vitro mediate 89.6 infection in lymphoid tissue. We also demonstrate that restricted coreceptor use in lymphoid tissue ex vivo compared with in vitro utilization occurs with other dual-tropic primary isolates and is not unique to 89.6. For all strains tested that are dual tropic in vitro, severe CD4 T cell depletion in lymphoid tissue correlated with preferential CXCR4 use in this ex vivo system.

Original languageEnglish
Pages (from-to)239-247
Number of pages9
JournalVirology
Volume281
Issue number2
DOIs
Publication statusPublished - 15 Mar 2001
Externally publishedYes

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Keywords

  • AMD3100
  • CCR5
  • Chemokine receptor
  • CXCR4
  • HIV
  • Pathogenesis
  • RANTES
  • T lymphocytes

ASJC Scopus subject areas

  • Virology

Cite this

Malkevitch, N., McDermott, D. H., Yi, Y., Grivel, J-C. B., Schols, D., De Clercq, E., Murphy, P. M., Glushakova, S., Collman, R. G., & Margolis, L. (2001). Coreceptor choice and T cell depletion by R5, X4, and R5X4 HIV-1 variants in CCR5-deficient (CCR5δ32) and normal human lymphoid tissue. Virology, 281(2), 239-247. https://doi.org/10.1006/viro.2000.0807