Altered pattern in viral mRNA expression of Iranian type HTLV-1 leading to enhanced viral expression

Abstract

Risk for HAM/TSP development is known to differ among the subtypes of HTLV-1. In Japan, incident rate of HAM/ TSP in carrier people infected with cosmopolitan type A is 2.5 times higher than those with cosmopolitan type B. Although HTLV-1 of cosmopolitan type A is also prevalent in Jamaica and northern part of Iran, the rate of HAM/TSP development in this area is much higher than in Japan. Several polymorphisms in nucleotide sequence were found in pX region in Jamaican and Iranian type A compared to those in Japanese type A. These sequences include the substitution of stop codon to Trp codon, leading to extension of 20 a.a. in C-terminal of Rex. To assess the effect of these sequences on viral replication, we constructed the infectious clone harboring either Japanese type A (JP) or Jamaican/Iranian (J/I) pX sequences. Viral production from infectious clones in transiently transfected 293T cells was evaluated by p19 ELISA assay and J/I type virus was found to be produced higher than JP type. The virus produced in 293T cells was used to establish HTVL-1 infected Jurkat cell lines and viral mRNA expression was analyzed. In J/I type cell lines, full length mRNA was expressed more than doublyspliced pX mRNA, whereas JP type cell lines exhibited the opposite pattern of mRNA expression. These results indicate that the higher viral production of J/I type should result from distinct post-transcriptional control most provably due to the difference in Rex protein. We are currently investigating the molecular mechanism of this phenomenon.