Frequency of p12K and p12R alleles of HTLV Type 1 in HAM/TSP patients and in asymptomatic HTLV type 1 carriers.

Abstract

HTLV-1 has a complex genome, and contains four open reading frames (ORFs) in the 3' region encoding viral and cellular regulatory proteins. p12 is a small, ORF I-encoded hydrophobic protein, the function of which is not well understood. It has been shown that p12 enhances the E5-transforming ability of bovine papillomavirus; and binds to the 16-kDa subunit of the vacuolar ATPase pump, immature forms of the beta and gamma(c) chains of the interleukin 2 receptor, and the free chain of MHC I. p12 carrying a lysine residue (p12K) at position 88 of its sequence may be rapidly degraded in the cell via proteasome, whereas p12 with an arginine residue (p12R) at the same position is severalfold more stable. These alleles are found in proviral DNA of HTLV-1-infected individuals and it was previously observed that the p12K allele was more frequent in HAM/TSP (HTLV-1-associated myelopathy/tropical spastic paraparesis) patients and was not found at all in asymptomatic carriers, whereas patients with adult T cell leukemia/lymphoma (ATLL) carry the p12R allele. To extend these observations and verify whether the p12K mutation could be used as a marker of progression to HAM/TSP, we analyzed 37 HAM/TSP patients and 40 asymptomatic carriers at different stages of infection. In our cohort, only one HAM/TSP patient carried the p12K phenotype, which accounted for a frequency of 2.7% (1 of 37). We also found, among the 40 asymptomatic HTLV-1 carriers, one who presented the p12K phenotype, contrasting with previous publications. Thus, p12K does not seem to be universally diagnostic for HTLV-1-associated neurological disease. Further screening of HTLV-1-infected individuals in other populations may elucidate this observation.