Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta. 2000

R Kitai, and M L Zhao, and N Zhang, and L L Hua, and S C Lee
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

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.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015213 Neuroimmunomodulation The biochemical and electrophysiological interactions between the NERVOUS SYSTEM and IMMUNE SYSTEM. Cholinergic Anti-inflammatory Pathway,Neuro-immune Axis,Neuro-immune Communication,Neuro-immune Interactions,Neuro-immunomodulation,Neuroimmune Axis,Neuroimmune Communication,Neuroimmune Interactions,Neuroimmune Processes,Vagal Anti-inflammatory Pathway,Vagal-immune Interactions,Neuroimmune Mechanisms,Neuroimmune Process,Anti-inflammatory Pathway, Cholinergic,Anti-inflammatory Pathway, Vagal,Cholinergic Anti inflammatory Pathway,Cholinergic Anti-inflammatory Pathways,Communication, Neuro-immune,Communication, Neuroimmune,Interaction, Neuro-immune,Interaction, Neuroimmune,Mechanism, Neuroimmune,Neuro immune Axis,Neuro immune Communication,Neuro immune Interactions,Neuro immunomodulation,Neuro-immune Communications,Neuro-immune Interaction,Neuroimmune Communications,Neuroimmune Interaction,Neuroimmune Mechanism,Process, Neuroimmune,Vagal Anti inflammatory Pathway,Vagal Anti-inflammatory Pathways,Vagal immune Interactions,Vagal-immune Interaction
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015526 AIDS Dementia Complex A neurologic condition associated with the ACQUIRED IMMUNODEFICIENCY SYNDROME and characterized by impaired concentration and memory, slowness of hand movements, ATAXIA, incontinence, apathy, and gait difficulties associated with HIV-1 viral infection of the central nervous system. Pathologic examination of the brain reveals white matter rarefaction, perivascular infiltrates of lymphocytes, foamy macrophages, and multinucleated giant cells. (From Adams et al., Principles of Neurology, 6th ed, pp760-1; N Engl J Med, 1995 Apr 6;332(14):934-40) AIDS Encephalopathy,Dementia Complex, AIDS-Related,HIV Dementia,HIV Encephalopathy,HIV-1-Associated Cognitive Motor Complex,HIV-Associated Cognitive Motor Complex,AIDS-Related Dementia Complex,Acquired-Immune Deficiency Syndrome Dementia Complex,Dementia Complex, Acquired Immune Deficiency Syndrome,Encephalopathy, AIDS,Encephalopathy, HIV,HIV-1 Cognitive and Motor Complex,AIDS Encephalopathies,AIDS Related Dementia Complex,Complex, AIDS Dementia,Complex, AIDS-Related Dementia,Dementia Complex, AIDS,Dementia Complex, AIDS Related,Dementia, HIV,Dementias, HIV,Encephalopathies, AIDS,Encephalopathies, HIV,HIV 1 Associated Cognitive Motor Complex,HIV 1 Cognitive and Motor Complex,HIV Associated Cognitive Motor Complex,HIV Dementias,HIV Encephalopathies
D015700 HIV Envelope Protein gp41 Transmembrane envelope protein of the HUMAN IMMUNODEFICIENCY VIRUS which is encoded by the HIV env gene. It has a molecular weight of 41,000 and is glycosylated. The N-terminal part of gp41 is thought to be involved in CELL FUSION with the CD4 ANTIGENS of T4 LYMPHOCYTES, leading to syncytial formation. Gp41 is one of the most common HIV antigens detected by IMMUNOBLOTTING. Envelope Protein gp41, HIV,HIV Transmembrane Protein gp41,HTLV-III gp41,env Protein gp41, HIV,gp41(HIV),gp41 Envelope Protein, HIV

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