Purinergic receptors are required for HIV-1 infection of primary human macrophages

Joy E. Hazleton, Joan W. Berman, Eliseo A. Eugenin

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Macrophages play a significant role in HIV infection, viral rebound, and the development of AIDS. However, the function of host proteins in viral replication is incompletely characterized in macrophages. Purinergic receptors P2X and P2Y are major components of the macrophage immune response to pathogens, inflammation, and cellular damage. We demonstrate that these receptors are necessary for HIV infection of primary human macrophages. Inhibition of purinergic receptors results in a significant reduction in HIV replication in macrophages. This inhibition is independent of viral strain and is dose dependent. We also identify that P2X 1, P2X 7, and P2Y 1 receptors are involved in viral replication. We show that P2X 1, but not P2X 7 or P2Y 1, is necessary for HIV entry into macrophages. We demonstrate that interaction of the HIV surface protein gp120 with macrophages stimulates an increase in ATP release. Thus, we propose that HIV's binding to macrophages triggers a local release of ATP that stimulates purinergic receptors and facilitates HIV entry and subsequent stages of viral replication. Our data implicate a novel role for a family of host proteins in HIV replication in macrophages and suggest new therapeutic targets to reduce the devastating consequences of HIV infection and AIDS.

Original languageEnglish (US)
Pages (from-to)4488-4495
Number of pages8
JournalJournal of Immunology
Volume188
Issue number9
DOIs
StatePublished - May 1 2012

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Purinergic Receptors
HIV Infections
HIV-1
Macrophages
HIV
Human Immunodeficiency Virus Proteins
Purinergic P2Y Receptors
Acquired Immunodeficiency Syndrome
Purinergic P2X Receptors
Adenosine Triphosphate
Viral Proteins
Membrane Proteins
Inflammation

ASJC Scopus subject areas

  • Immunology

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Purinergic receptors are required for HIV-1 infection of primary human macrophages. / Hazleton, Joy E.; Berman, Joan W.; Eugenin, Eliseo A.

In: Journal of Immunology, Vol. 188, No. 9, 01.05.2012, p. 4488-4495.

Research output: Contribution to journalArticle

Hazleton, Joy E. ; Berman, Joan W. ; Eugenin, Eliseo A. / Purinergic receptors are required for HIV-1 infection of primary human macrophages. In: Journal of Immunology. 2012 ; Vol. 188, No. 9. pp. 4488-4495.
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