Role of the β-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia

Anuja Ghorpade, Meng Q.I. Xia, Bradley T. Hyman, Yuri Persidsky, Adeline Nukuna, Paul Bock, Myhanh Che, Jenae Limoges, Howard E. Gendelman, Charles R. Mackay

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection in mononuclear phagocyte lineage cells (monocytes, macrophages, and microglia) is a critical component in the pathogenesis of viral infection. Viral replication in macrophages serves as a reservoir, a site of dissemination, and an instigator for neurological sequelae during HIV-1 disease. Recent studies demonstrated that chemokine receptors are necessary coreceptors for HIV-1 entry which determine viral tropism for different cell types. To investigate the relative contribution of the β-chemokine receptors CCR3 and CCR5 to viral infection of mononuclear phagocytes we utilized a panel of macrophage-tropic HIV-1 strains (from blood and brain tissue) to infect highly purified populations of monocytes and microglia. Antibodies to CD4 (OKT4A) abrogated HIV-1 infection. The β chemokines and antibodies to CCR3 failed to affect viral infection of both macrophage cell types. Antibodies to CCR5 (3A9) prevented monocyte infection but only slowed HIV replication in microglia. Thus, CCR5, not CCR3, is an essential receptor for HIV-1 infection of monocytes. Microglia express both CCR5 and CCR3, but antibodies to them fail to inhibit viral entry, suggesting the presence of other chemokine receptors for infection of these cells. These studies demonstrate the importance of mononuclear phagocyte heterogeneity in establishing HIV-1 infection and persistence.

Original languageEnglish (US)
Pages (from-to)3351-3361
Number of pages11
JournalJournal of virology
Volume72
Issue number4
DOIs
StatePublished - Apr 1998

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Ghorpade, A., Xia, M. Q. I., Hyman, B. T., Persidsky, Y., Nukuna, A., Bock, P., Che, M., Limoges, J., Gendelman, H. E., & Mackay, C. R. (1998). Role of the β-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia. Journal of virology, 72(4), 3351-3361. https://doi.org/10.1128/jvi.72.4.3351-3361.1998