Regulation of the human neurotropic virus promoter by JCV-T antigen and HIV-1 tat protein.
We compared the ability of HIV-1 tat protein and JCV T-antigen in inducing transcription from the JCV late promoter, JCVL. A JCVL promoter-chloramphenicol acetyltransferase plasmid (pJCL-CAT) was transfected into human glial cells alone or together with plasmids producing T-antigen and tat protein. CAT enzyme activity obtained from the transfected cells indicated that both JCV T-antigen and HIV-1 tat proteins stimulated JCV late gene expression. However, the level of induction mediated by tat protein was significantly higher than that obtained with T-antigen. Moreover, in contrast to JCV T-antigen, tat stimulated JCVL-promoter activity over a narrow range of ptat expressor plasmid concentration. Co-transfection of both T-antigen and tat plasmids at optimal concentrations resulted in greater than additive CAT activity from the JCVL promoter. This synergism suggests that the two activator proteins utilize alternative mechanisms to exert their effects. Using deletion mutations from the 5' end of the JCVL promoter, we demonstrated that different regions within the JCV enhancer/promoter are important for T-antigen and tat induction, implying that these activators function through distinct targets to increase JCVL promoter activity.
Chowdhury
M
M
Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-6799.
Taylor
J P
JP
Tada
H
H
Rappaport
J
J
Wong-Staal
F
F
Amini
S
S
Khalili
K
K
D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D015696:Gene Products, tat / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000201:enzymology / Q000502:physiology; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus
D000952:Antigens, Polyomavirus Transforming; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase