TY - JOUR
T1 - Role of MIP-1β and RANTES in HIV-1 infection of microglia
T2 - Inhibition of infection and induction by IFNβ
AU - Kitai, Ryuhei
AU - Zhao, Meng Liang
AU - Zhang, Nan
AU - Hua, Liwei L.
AU - Lee, Sunhee C.
N1 - Funding Information:
The authors thank Karen Weidenheim, director of the Einstein Human Fetal Tissue Repository for fetal tissues, Wa Shen for microglial cultures, and the NIH AIDS Research and Reference Reagent Program for the virus, recombinant chemokines and antibodies. The authors greatly appreciate the help of Harris Goldstein and Massimo Pettoello-Mantovani for preparation of HIV-1 cultures in the initial phases of this study, and Judy Liu and Celia Brosnan for many insightful discussions. This study was supported by the NIH grant MH55477. NZ was supported by NS07098.
PY - 2000/10/2
Y1 - 2000/10/2
N2 - 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-1β, also potently inhibited HIV-1 infection in microglia, but the third ligand MIP-1α 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-1β, but not by anti-MIP-1α. These results demonstrate the presence of endogenous chemokines that act as endogenous inhibitors of HIV-1 infection in microglia. Additionally, IFNβ, 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.
AB - 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-1β, also potently inhibited HIV-1 infection in microglia, but the third ligand MIP-1α 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-1β, but not by anti-MIP-1α. These results demonstrate the presence of endogenous chemokines that act as endogenous inhibitors of HIV-1 infection in microglia. Additionally, IFNβ, 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.
KW - AIDS
KW - Brain
KW - Chemokine
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U2 - 10.1016/S0165-5728(00)00315-5
DO - 10.1016/S0165-5728(00)00315-5
M3 - Article
C2 - 11024554
AN - SCOPUS:0034596585
SN - 0165-5728
VL - 110
SP - 230
EP - 239
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -
