Transcription and replication of human immunodeficiency virus-1 in B lymphocytes in vitro.
We and others have shown that HIV-1 transcription and replication in vitro are increased by the binding of transcriptional enhancer DNA sequences in the HIV-1 long terminal repeat (LTR) to a cellular protein designated Nuclear Factor-kappa B (NF-kappa B), a trans-acting transcription factor which is present in activated but not in resting T cells. Because NF-kappa B is also expressed in resting B cells we suggested that B cells might provide an optimal intracellular environment for HIV-1 transcription. Using a transient transfection assay, we show that the HIV-1 LTR is indeed more efficiently transcribed in the B cell line Raji than in the T cell line Jurkat, and that this effect maps to the transcriptional enhancer (NF-kappa B binding site) of the LTR. Furthermore, we show that Raji cells which have been rendered CD4-positive by gene transfection are susceptible to HIV-1 infection, and that viral gene expression and replication are more efficient in these CD4-positive B cells than in CD4-positive T cells. These findings demonstrate the crucial role of the transcriptional enhancer in regulating HIV-1 expression and, since receptors for HIV-1 are expressed by some Epstein-Barr virus (EBV)-positive B cells, they also suggest that HIV-1 replication could occur in EBV-positive B cells in vivo.
Calman
A F
AF
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Busch
M P
MP
Vyas
G N
GN
McHugh
T M
TM
Stites
D P
DP
Peterlin
B M
BM
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000382:microbiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005814:Genes, Viral; D006678:HIV / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014779:Virus Replication
D000945:Antigens, Differentiation, T-Lymphocyte