Role of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia.
Human immunodeficiency virus type 1 (HIV-1) infection in mononuclear phagocyte lineage cells (monocytes, macrophages, and microglia) is a critical component in the pathogenesis of viral infection. Viral replication in macrophages serves as a reservoir, a site of dissemination, and an instigator for neurological sequelae during HIV-1 disease. Recent studies demonstrated that chemokine receptors are necessary coreceptors for HIV-1 entry which determine viral tropism for different cell types. To investigate the relative contribution of the beta-chemokine receptors CCR3 and CCR5 to viral infection of mononuclear phagocytes we utilized a panel of macrophage-tropic HIV-1 strains (from blood and brain tissue) to infect highly purified populations of monocytes and microglia. Antibodies to CD4 (OKT4A) abrogated HIV-1 infection. The beta chemokines and antibodies to CCR3 failed to affect viral infection of both macrophage cell types. Antibodies to CCR5 (3A9) prevented monocyte infection but only slowed HIV replication in microglia. Thus, CCR5, not CCR3, is an essential receptor for HIV-1 infection of monocytes. Microglia express both CCR5 and CCR3, but antibodies to them fail to inhibit viral entry, suggesting the presence of other chemokine receptors for infection of these cells. These studies demonstrate the importance of mononuclear phagocyte heterogeneity in establishing HIV-1 infection and persistence.
Ghorpade
A
A
Center for Neurovirology and Neurodegenerative Disorders and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198, USA.
Xia
M Q
MQ
Hyman
B T
BT
Persidsky
Y
Y
Nukuna
A
A
Bock
P
P
Che
M
M
Limoges
J
J
Gendelman
H E
HE
Mackay
C R
CR
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D018076:DNA, Complementary; D004279:DNA, Viral / Q000096:biosynthesis; D018792:Encephalitis, Viral / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000473:pathology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000821:virology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D016133:Polymerase Chain Reaction; D011817:Rabbits; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000502:physiology*; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000502:physiology*; D014771:Virion
C515350:CCR3 protein, human; C515351:Ccr3 protein, mouse; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018076:DNA, Complementary; D004279:DNA, Viral; D019402:Macrophage Inflammatory Proteins; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D054303:HIV Reverse Transcriptase