Noninfectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor

doi:10.1073/pnas.0611263104

Noninfectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor

*Molecular and Integrative Physiological Sciences, Department of Environmental Health,
^†Department of Immunology and Infectious Diseases, and
^‡Biomedical Imaging Laboratory, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115; and
^§Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

Communicated by Robert C. Gallo, University of Maryland, Baltimore, MD, January 8, 2007 (received for review January 16, 2006)

Abstract

Although protein receptors on the plasma membrane involved in the initial steps of productive HIV-1 infection have been well characterized, little is known about interactions between cellular carbohydrate receptors and HIV-1. Here, we report the involvement of a carbohydrate receptor, the macrophage mannose receptor (MR), and its role in supporting HIV-1 binding and entry. HIV-1 can enter the cytoplasm of human macrophages and microglia as well as murine macrophages by MR, although no subsequent viral replication was observed. Correspondingly, HIV-1 entry into Cos-7 cells after induction of expression of MR by transfection with MR-cDNA did not demonstrate viral replication. Our studies suggest that whereas MR may serve as a binding and an entry site, the MR-mediated pathway does not lead to productive HIV-1 infection. In addition, we report that recombinant HIV-1 gp120 blocks MR-mediated phagocytosis in human and murine alveolar macrophages and microglial cells. Therefore, characterization of the HIV-1 noninfectious MR-mediated phagocytic pathway may foster advances in HIV-1 vaccine design and an improved understanding of HIV-1/AIDS pathogenesis and host defenses.

Footnotes

^¶To whom correspondence should be addressed. E-mail: brain{at}hsph.harvard.edu
Author contributions: J.R.T., M.E., and J.D.B. designed research; J.R.T., R.R., R.M.M., F.D., and M.F.M. performed research; R.R. and F.D. contributed new reagents/analytic tools; J.R.T., R.R., R.M.M., F.D., M.F.M., M.E., and J.D.B. analyzed data; and J.R.T. and J.D.B. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0611263104/DC1.
Abbreviations:

PC,

Pneumocystis carinii;

MR,

mannose receptor;

rgp120,

recombinant HIV-1 gp120.
Freely available online through the PNAS open access option.