Isolation, cloning, and complete nucleotide sequence of a phenotypically distinct Brazilian isolate of human T-lymphotropic virus type II (HTLV-II)

Analysis of human T-lymphotropic virus type II (HTLV-II) isolates from Nort h America and Europe have demonstrated the existence of two molecular subty pes of the virus, HTLV-IIa and HTLV-IIb. Recently, studies on HTLV-II infec tions in Brazil have revealed isolates that are related phylogenetically to the HTLV-IIa subtype but have a HTLV-IIb phenotype with respect to the tra nsactivating protein, tax To more clearly define this relationship, HTLV-II was isolated from peripheral blood of an IVDA from Sao Paulo, Brazil (SP-W V), and the complete provirus was cloned and sequenced. Comparison of HTLV- IISP-WV nucleotide sequences to other available complete HTLV-II proviral s equences revealed that HTLV-IISP-WV is most closely related to HTLV-IIMor t he prototypic HTLV-IIa subtype sequence. Phylogenetic analysis of LTR, env and tax regions unequivocally demonstrated that HTLV-IISP-WV and all other Brazilian sequences examined are members of the IIa subtype. The predicted amino acid sequences of the major coding regions of HTLV-ISP-WV, are also m ost closely related to HTLV-IIMor with the important exception of tax. The tax protein encoded by HTLV-IISP-WV is 96-99% identical to the tax of IIb i solates and is similar in that it has an additional 25 amino acids at the c arboxy-terminus compared to the HTLV-II,, tax with which it shares 91% iden tity. Analysis of tax stop codon usage of a number of HTLV-IIa isolates fro m North American, Europe, and Brazil demonstrated that isolates from the la st region appear to be unique in their extended tax phenotype. It could be demonstrated that the extended tax proteins in the HTLV-llb and Brazilian i solates had equivalent ability to transactivate the viral LTR, and studies with deletion mutants indicated that the extended C-terminus is not essenti al for transactivation. In contrast, the HTLV-IIa tax was found to have a g reatly diminished ability to transactivate the viral LTR, which appeared to be a consequence of reduced expression of the protein. The studies show th at although the Brazilian strains do not represent an entirely new subtype based on nucleotide sequence analysis they are a phenotypically unique mole cular variant within the HTLV-IIa subtype. (C) 2000 Academic Press.