Human immunodeficiency virus type 1 tropism for brain microglial cells is determined by a region of the env glycoprotein that also controls macrophage tropism.
Human immunodeficiency virus type 1 (HIV-1), the agent of AIDS, frequently infects the central nervous system. We inoculated adult human brain cultures with chimeric viruses containing parts of the env gene of a cloned primary isolate from brain tissue, HIV-1 JRFl, inserted into the cloned DNA of a T-cell-tropic strain. A chimeric virus containing the carboxy-terminal portion of HIV-1 JRFl env did not replicate in these brain tissue cultures, while a chimera expressing an env-encoded protein containing 158 amino acids of HIV-1 JRFl gp120, including the V3 loop, replicated well in brain microglial cells, as it does in blood macrophages. Infection of brain microglial cells with such a chimera was blocked by an antibody to the V3 loop of gp 120. Thus, env determinants in the region of gp120, outside the CD4-binding site and comprising the V3 loop, are critical for efficient viral binding to and/or entry into human brain microglia.
Sharpless
N E
NE
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
O'Brien
W A
WA
Verdin
E
E
Kufta
C V
CV
Chen
I S
IS
Dubois-Dalcq
M
M
D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000382:microbiology*; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004279:DNA, Viral; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000382:microbiology*; D010446:Peptide Fragments / Q000378:metabolism; D011533:Proviruses / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D015704:CD4 Antigens; D004279:DNA, Viral; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins