Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta.
Microglia are the major target of HIV-1 infection in the brain. Microglial infection is CD4-dependent, but the role of chemokine receptors CCR5 and CCR3 and their natural ligands in modulating HIV-1 infection in microglia has been questioned. In primary human fetal microglial cultures, we demonstrate that HIV-1 infection of these cells is dependent on CCR5, since an antibody to CCR5 completely blocked productive infection. Anti-CCR3, in contrast, had a smaller inhibitory effect which was not statistically significant. The chemokine ligands for CCR5, RANTES and MIP-1beta, also potently inhibited HIV-1 infection in microglia, but the third ligand MIP-1alpha failed to show inhibition. Interestingly, when microglial cultures were treated with antibodies specific to each of these chemokines, HIV-1 infection was enhanced by anti-RANTES and anti-MIP-1beta, but not by anti-MIP-1alpha. These results demonstrate the presence of endogenous chemokines that act as endogenous inhibitors of HIV-1 infection in microglia. Additionally, IFNbeta, a known anti-viral cytokine, also provided potent inhibition of viral infection as well as induction of all three chemokines in microglia. These results suggest the possibility that type I interferon can down-modulate microglial HIV-1 infection in vivo by multiple mechanisms.
Kitai
R
R
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Zhao
M L
ML
Zhang
N
N
Hua
L L
LL
Lee
S C
SC
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001921:Brain / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000276:immunology*; D015726:Giant Cells / Q000276:immunology / Q000821:virology; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000276:immunology*; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000821:virology*; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology; D019713:Receptors, CCR5 / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
D000998:Antiviral Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D015700:HIV Envelope Protein gp41; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D016899:Interferon-beta