Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent.
In the central nervous system of AIDS patients, human immunodeficiency virus (HIV) infects primarily microglia, a cell type of bone marrow origin. Moreover, microglial cells isolated from adult human brain support the replication of macrophage-adapted strains of HIV type 1 (HIV-1) (B.A. Watkins, H.H. Dorn, W.B. Kelly, R.C. Armstrong, B. Potts, F. Michaels, C.V. Kufta, and M. Dubois-Dalcq, Science 249:549-553, 1990). To determine whether the CD4 receptor, which is expressed in brain, mediates the entry of HIV-1 in microglial cells, we analyzed CD4 transcript expression in cultured microglia using highly sensitive polymerase chain reaction detection of cDNAs synthesized from RNA. With this method, CD4 transcripts could be detected in cultured microglia--as well as in various human brain regions and cultured macrophages used as positive controls--along with transcripts for the LDL and Fc receptors which are characteristic of cells of the macrophage lineage. We then attempted to block viral entry into microglial cells using anti-CD4 antibodies or soluble CD4 (sCD4), which recognize binding sites on CD4 and HIV-1 glycoprotein gp120, respectively. Cultures were pretreated with blocking antibodies (Leu-3a, OKT4A) or virus was preincubated with sCD4 prior to infection with HIV-1 strain AD87(M) or BaL. With either viral strain, these treatments resulted in the prevention of infection or significant and dose-dependent reduction in the number of infected cells and in the levels of reverse transcriptase or p24 antigen released in the medium. Thus, brain-derived microglial cells, which are the primary target of HIV-1 infection in the brain, express the CD4 receptor and this receptor is effectively used for viral entry in vitro.
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
C A
CA
Jordan
B A
BA
Watkins
C
C
Kufta
M
M
Dubois-Dalcq
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D000328:Adult; D001483:Base Sequence; D001921:Brain / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics*; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008297:Male; D008648:Mesoderm; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic; D014779:Virus Replication
D015704:CD4 Antigens; D015345:Oligonucleotide Probes; D012313:RNA