TAR-independent replication of human immunodeficiency virus type 1 in glial cells.
The molecular mechanisms involved in the replication of human immunodeficiency virus type 1 (HIV-1) may differ in various cell types and with various exogenous stimuli. Astrocytic glial cells, which can support HIV-1 replication in cell cultures and may be infected in vivo, are demonstrated to provide a cellular milieu in which TAR mutant HIV-1 viruses may replicate. Using transfections of various TAR mutant HIV-1 proviral constructs, we demonstrate TAR-independent replication in unstimulated astrocytic cells. We further demonstrate, using viral constructs with mutations in the tat gene and in the nuclear factor kappa B (NF-kappa B)-binding sites (enhancer) of the HIV-1 long terminal repeat, that TAR-independent HIV-1 replication in astrocytic cells requires both intact NF-kappa B moiety-binding motifs in the HIV-1 long terminal repeat and Tat expression. We measured HIV-1 p24 antigen production, syncytium formation, and levels and patterns of viral RNA expression by Northern (RNA) blotting to characterize TAR-independent HIV-1 expression in astrocytic glial cells. This alternative regulatory pathway of TAR-independent, Tat-responsive viral production may be important in certain cell types for therapies which seek to perturb Tat-TAR binding as a strategy to interrupt the viral lytic cycle.
Bagasra
O
O
Dorrance H. Hamilton Laboratories, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-6799.
Khalili
K
K
Seshamma
T
T
Taylor
J P
JP
Pomerantz
R J
RJ
D001253:Astrocytes / Q000382:microbiology*; D015152:Blotting, Northern; D002460:Cell Line; D015726:Giant Cells / Q000166:cytology / Q000382:microbiology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009457:Neuroglia / Q000382:microbiology*; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014779:Virus Replication; D000099253:Trans-Activation Responsive RNA-Binding Protein
D012367:RNA, Viral; D016601:RNA-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D000099253:Trans-Activation Responsive RNA-Binding Protein