c-Myb influences HIV type 1 gene expression and virus production.
c-Myb is expressed in proliferating T cells. Fifteen c-Myb-binding sites can be identified in the HIV-1 long terminal repeat (LTR), suggesting that c-Myb may regulate HIV-1 gene expression and virus replication. Increasing the cellular levels of c-Myb by transient transfection of CEM cells resulted in a 10- to 20-fold activation of HIV-1 LTR-driven gene expression and mutation of one high-affinity Myb-binding site within the LTR reduced this activation by 60 to 70%. Conversely, inhibition of c-Myb expression in MT-2 cells by treatment with c-myb antisense oligonucleotides decreased HIV-1 replication by 85%, as measured by reverse transcriptase activity and cytopathic effects. The effect of c-myb antisense oligonucleotides on HIV-1 gene expression and virus particle production appeared to be independent of cell proliferation, but dependent on the presence of c-Myb activity mediated through the HIV-1 LTR. These data show that c-myb expression affects HIV-1 replication in CD4(+) T cells.
Churchill
M J
MJ
AIDS Molecular Biology Unit, National Centre in HIV Virology Research, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria 3078, Australia. churchil@burnet.edu.au
Ramsay
R G
RG
Rhodes
D I
DI
Deacon
N J
NJ
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism / Q000494:pharmacology*; D015533:Transcriptional Activation; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D020598:Proto-Oncogene Proteins c-myb