Comparison of CREB- and NF-kappaB-mediated transactivation by human T lymphotropic virus type II (HTLV-II) and type I (HTLV-I) tax proteins.
The function of the transactivator protein Tax from HTLV-II subtype A, subtype B, Brazilian subtype C, and African subtype D isolates was compared to that of Tax from an HTLV-I isolate. HTLV-II subtypes A, B, and C were less active in the transactivation of a NF-kappaB reporter compared to HTLV-I Tax in 293T but not Jurkat T cells. In both cell types there were no significant differences between the functions of HTLV-II B, C, and D and HTLV-I Tax proteins on either a full-length HTLV-I LTR or a 21-bp repeat reporter, suggesting that there is equivalent CREB-mediated transactivation between the viruses and these subtypes. In contrast, Tax of some but not all HTLV-II subtype A isolates, including the prototype Mo, had a greatly decreased ability to transactivate, and this could be directly correlated with a decrease in protein expression. Employment of cDNA clones encoding both Rex and Tax demonstrated that Rex was unable to rescue the expression or activity of the IIA Mo isolate. These studies demonstrate that with the exception of some HTLV-IIA subtypes there are no significant differences in Tax transactivation via the CREB and NF-kappaB pathways between the two viruses and suggest that the HTLV-II Tax may have a pathogenic potential equivalent to that of HTLV-I.
Lewis
Martha J
MJ
Department of Medical Microbiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, 4, Ireland.
Sheehy
Noreen
N
Salemi
Marco
M
VanDamme
Anne-Mieke
AM
Hall
William W
WW
D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism; D015367:Human T-lymphotropic virus 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics*; D015533:Transcriptional Activation
D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D016328:NF-kappa B