MOLECULAR ANALYSIS OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-II FROM WAYUU-INDIANS-OF-COLOMBIA DEMONSTRATES 2 SUBTYPES OF HTLV-IIB

Studies of the genetic heterogeneity of human T-cell lymphotropic viru s type II (HTLV-II) have revealed the presence of two genetic subtypes , termed HTLV-IIa and HTLV-IIb. The HTLV-IIb subtype encodes an immuno dominant epitope present at the C terminus of the extended Tax protein and, by using an LTR-based, restriction fragment-length polymorphism (RFLP) assay, can be further classified into IIb0-IIb5, with HTLV-IIb1 (Central Amerindian-like) and HTLV-IIb5 (North Amerindian-like) being characteristic subtypes for Native American Indians. To determine the antigenic and genetic heterogeneity among HTLV-II-infected South Amer indians, we used a Tax synthetic peptide immunoassay on serum, and RFL P and phylogenetic analysis on LTR sequences amplified from genomic DN A from four Wayuu Indians of Colombia. The Wayuu specimens displayed s eroreactivity to the immunodominant epitope located in the extended Ta x region, as predicted, and demonstrated genetic heterogeneity by the presence of both the IIb1 (Wyu1, Zuc31) and IIb5 (Wyu2, Zuc42) subtype s of HTLV-II. This genetic diversity was further supported by clusteri ng of the Wyu1 and Wyu2 LTR sequences within separate phylogroups repr esented by the Guaymi Indian (IIb1) and North Amerindian (IIb5) sequen ces, respectively. Sequence analysis showed that major LTR regulatory motifs and the cis-acting repressive elements in the LTR RNA secondary structure were relatively conserved in both Wayuu subtypes, but the p redicted secondary structure of the rex response stem loop in the Wyu2 (IIb5) LTR sequence was 45 nucleotides (nt) and 95 nt longer than tha t observed in the Wyu1 (IIb1) and G12.1 (IIb1) LTR sequences, respecti vely. These results extend our knowledge of the genetic heterogeneity of HTLV-II in South Amerindians.