A high proportion of early response genes are constitutively activated in T cells by HTLV-I.
Immortalization of T cells by HTLV-I is mediated by the X region of the virus and probably involves transactivation of cellular genes. We show that T cells transformed by HTLV-I constitutively express a high proportion of early response genes that are normally transiently induced following antigenic or mitogenic activation of T cells. Thus, HTLV-I-infected T cells display an 'early activation' phenotype that is distinct from the gene expression pattern of continuously dividing T cells. Ten early response genes representing a diverse array of functional categories were assayed. Four DNA-binding proteins/transcription factors including the p50 subunit of NF-kappa B were evaluated. A protein(s) encoded by the X region of HTLV-I appeared to contribute to up-regulated expression of most, if not all, of the early response genes. For those genes that could be assayed, increased transcriptional rates, but not substantial changes in mRNA half-life, were demonstrated in the presence of pX-encoded proteins, suggesting that the transcriptional transactivator, Tax, affects the induction or maintenance of transcription for these mitogen-inducible genes. Therefore, Tax may mimic or interact with a component(s) of the signal transduction pathway activated by antigen or mitogen treatment. These data demonstrate that early response genes, some of which probably play roles in initiating or maintaining cellular proliferation, are frequent targets of HTLV-I activation.
Kelly
K
K
Laboratory of Pathology, NCI, NIH, Bethesda, Maryland 20892.
Davis
P
P
Mitsuya
H
H
Irving
S
S
Wright
J
J
Grassmann
R
R
Fleckenstein
B
B
Wano
Y
Y
Greene
W
W
Siebenlist
U
U
D015152:Blotting, Northern; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D016356:Gene Products, tax / Q000235:genetics*; D005814:Genes, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D013601:T-Lymphocytes / Q000382:microbiology*; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D016356:Gene Products, tax; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; C059786:transactivator protein p38(tax)