Thioredoxin-mediated redox control of human T cell lymphotropic virus type I (HTLV-I) gene expression.
Thioredoxin (TRX) is a small ubiquitous protein with multiple biological functions, including the thiol-mediated redox-regulation of gene expression. We have previously demonstrated that human TRX is overexpressed as a major protein oxidoreductase in human T cell lymphotropic virus type I (HTLV-I)-infected cells. In the present study, we investigated the relationship between TRX and viral gene expression in HTLV-I infection. To study the mechanism that causes overexpression of TRX in HTLV-I-infected cells, we first examined the effect of the HTLV-I transactivator, Tax, on TRX expression. Induction of HTLV-I Tax protein increased the expression of TRX protein in a Tax-transfected Jurkat cell line, JPX-9. Moreover, chloramphenicol acetyltransferase (CAT) analysis with a reporter gene containing the TRX promoter revealed that Tax activates the transcription of TRX gene. To study the role of overexpressed TRX in HTLV-I infection, we next examined the effect of TRX on HTLV-I long terminal repeat (LTR)-mediated transcription using CAT analysis. In an HTLV-I-infected human T cell line MT-2, the HTLV-I LTR transactivation was suppressed by the overexpression of wild-type TRX, but activated by the introduction of inactive mutant TRX. Moreover, in HTLV-I negative Jurkat T cells, the HTLV-I LTR transactivation induced by Tax was also repressed by overexpression of wild-type TRX. Because cellular redox changes were shown to affect the HTLV-I gene expression, it is likely that TRX modulates the HTLV-I gene expression by regulating cellular redox state. Taken together, these findings suggest that overexpressed TRX, which is induced by HTLV-I Tax, may play an important role in HTLV-I infection through the negative regulation of viral gene expression.
Sasada
Tetsuro
T
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan.
Nakamura
Hajime
H
Masutani
Hiroshi
H
Ueda
Shugo
S
Sono
Hiroshi
H
Takabayashi
Arimichi
A
Yodoi
Junji
J
D015967:Gene Expression Regulation, Viral / Q000502:physiology; D016355:Genes, pX; D015490:HTLV-I Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D010084:Oxidation-Reduction; D013601:T-Lymphocytes / Q000502:physiology / Q000821:virology*; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D014779:Virus Replication / Q000235:genetics
D013879:Thioredoxins