Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes

Barbara Sherry, Gabriele Zybarth, Massimo Alfano, Larisa Dubrovsky, Robert Mitchell, Daniel Rich, Peter Ulrich, Richard Bucala, Anthony Cerami, Michael Bukrinsky

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Cyclophilins are a family of proteins that bind cyclosporin A (CsA) and possess peptidyl-prolyl cis-trans isomerase activity. In addition, they are secreted by activated cells and act in a cytokine-like manner, presumably via signaling through a cell surface cyclophilin receptor. More recently, host- derived cyclophilin A (CyPA) has been shown to be incorporated into HIV-1 virions and its incorporation essential for viral infectivity. Here we present evidence supporting a role for viral-associated CyPA in the early events of HIV-1 infection. We report that HIV-1 infection of primary peripheral blood mononuclear cells can be inhibited by: (i) an excess of exogenously added CyPA; (ii) a CsA analogue unable to enter the cells; (iii) neutralizing antibodies to CyPA. Taken together with our observations that recombinant CyPA-induced mobilization of calcium in immortalized, as well as primary, CD4+ T lymphocytes, and that incubation of T cells with iodinated CyPA, followed by chemical cross-linking, resulted in the formation of a high molecular mass complex on the cell surface, these results suggest that HIV- 1-associated CyPA mediates an early event in viral infection via interaction with a cellular receptor. This interaction may present a target for anti-HIV therapies and vaccines.

Original languageEnglish
Pages (from-to)1758-1763
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
Publication statusPublished - Feb 17 1998

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Cyclophilin A
HIV-1
Macrophages
T-Lymphocytes
Cyclophilins
Cyclosporine
HIV Infections
Peptidylprolyl Isomerase
AIDS Vaccines
Cell Surface Receptors
Virus Diseases
Neutralizing Antibodies
Virion
Blood Cells
Cytokines
Calcium

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes. / Sherry, Barbara; Zybarth, Gabriele; Alfano, Massimo; Dubrovsky, Larisa; Mitchell, Robert; Rich, Daniel; Ulrich, Peter; Bucala, Richard; Cerami, Anthony; Bukrinsky, Michael.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 4, 17.02.1998, p. 1758-1763.

Research output: Contribution to journalArticle

Sherry, B, Zybarth, G, Alfano, M, Dubrovsky, L, Mitchell, R, Rich, D, Ulrich, P, Bucala, R, Cerami, A & Bukrinsky, M 1998, 'Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes', Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 4, pp. 1758-1763. https://doi.org/10.1073/pnas.95.4.1758
Sherry, Barbara ; Zybarth, Gabriele ; Alfano, Massimo ; Dubrovsky, Larisa ; Mitchell, Robert ; Rich, Daniel ; Ulrich, Peter ; Bucala, Richard ; Cerami, Anthony ; Bukrinsky, Michael. / Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 4. pp. 1758-1763.
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