Molecular mechanisms of regulation of HTLV-1 gene expression and its association with leukemogenesis.
Human T-cell leukemia virus type 1 (HTLV-1) has two trans-acting regulator genes, tax and rex, in the pX region. The tax gene is a trans-acting transcriptional activator of the long terminal repeat (LTR) and also of the cellular gene for IL-2R alpha. The latter seems to explain initiation of abnormal growth of HTLV-1 infected cells. The rex gene is a posttranscriptional regulator accumulating gag and env mRNA and also indirectly suppressing the transcription. The regulation requires two cis-acting elements, the LTR sequence at the 3' terminus and 5' splice signal, suggesting a novel mechanism of RNA processing in the nucleus. These two trans-activator genes are essential for efficient replication of HTLV-1 and also explain its poor replication competence and tendency to be latent in vivo.
Yoshida
M
M
Department of Viral Oncology, Cancer Institute, Tokyo, Japan.
Inoue
J
J
Fujisawa
J
J
Seiki
M
M
D000818:Animals; D002460:Cell Line; D015973:Gene Expression Regulation, Leukemic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D012326:RNA Splicing; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D012191:Retroviridae Proteins / Q000235:genetics* / Q000502:physiology; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation; D014779:Virus Replication
D016356:Gene Products, tax; D015375:Receptors, Interleukin-2; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors