Noninfectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor.
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.
Trujillo
J Roberto
JR
Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Rogers
Rick
R
Molina
Ramon M
RM
Dangond
Fernando
F
McLane
Mary Fran
MF
Essex
Max
M
Brain
Joseph D
JD
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000821:virology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000378:metabolism; D015699:HIV Envelope Protein gp120; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000382:microbiology / Q000821:virology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000382:microbiology / Q000821:virology; D008954:Models, Biological; D010587:Phagocytosis; D045363:Pneumocystis carinii; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D053586:Virus Internalization
D018076:DNA, Complementary; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins