Human T-cell lymphotropic virus type 3: complete nucleotide sequence and characterization of the human tax3 protein.
We and others have recently uncovered the existence of human T-cell lymphotropic virus type 3 (HTLV-3), the third member of the HTLV family. We have now sequenced the full-length HTLV-3Pyl43 provirus. As expected, HTLV-3Pyl43 contains open reading frames corresponding to the gag, pol, env, tax, and rex genes. Interestingly, its long terminal repeat (LTR) includes only two Tax-responsive elements, as is the case for type 3 simian T-cell lymphotropic viruses (STLV-3). Phylogenetic analyses reveal that HTLV-3Pyl43 is closely related to central African STLV-3. Unexpectedly, the proximal pX region of HTLV-3Pyl43 lacks 366 bp compared to its STLV-3 counterpart. Because of this deletion, the previously described RorfII sequence is lacking. At the amino acid level, Tax3Pyl43 displays strong similarities with HTLV-1 Tax, including the sequence of a PDZ class I binding motif. In transient-transfection assays, Tax3Pyl43 activates the transcriptions from HTLV-3, HTLV-1, and HTLV-2 LTRs. Mutational analysis indicates that two functional domains (M22 and M47) important for transactivation through the CREB/ATF or NF-kappaB pathway are similar but not identical in Tax1 and Tax3Pyl43. We also show that Tax3Pyl43 transactivates the human interleukin-8 and Bcl-XL promoters through the induction of the NF-kappaB pathway. On the other hand, Tax3Pyl43 represses the transcriptional activity of the p53 tumor suppressor protein as well as the c-Myb promoter. Altogether, these results demonstrate that although HTLV-3 and HTLV-1 have only 60% identity, Tax3Pyl43 is functionally closely related to the transforming protein Tax1 and suggest that HTLV-3, like HTLV-1, might be pathogenic in vivo.
Calattini
Sara
S
Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS URA 1930, Département de Virologie, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France. .
Chevalier
Sébastien Alain
SA
Duprez
Renan
R
Afonso
Philippe
P
Froment
Alain
A
Gessain
Antoine
A
Mahieux
Renaud
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016679:Genome, Viral / Q000235:genetics; D006678:HIV / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
D016209:Interleukin-8; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D051020:bcl-X Protein