FAMILIAL TRANSMISSION AND MINIMAL SEQUENCE VARIABILITY OF HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) IN ZAIRE

Our group previously reported a strong familial clustering of HTLV-I-a ssociated myelopathy/tropical spastic paraparesis (HAM/TSP) in Zaire, suggesting a familial transmission of the virus together with the pres ence of cofactors. In the present study among 84 relatives of 16 HTLV- I-positive or HAM/TSP index cases, we found that all 15 seropositive c hildren had a seropositive mother and that all 15 children with a sero positive father but a seronegative mother were seronegative. Lymphocyt es of 17 relatives from 2 families with a familial HTLV-I-associated n europathy were tested in 2 polymerase chain reaction (PCR) assays ampl ifying pol and tax/rex gene fragments. The 10 seropositive individuals were PCR positive for HTLV-I and the 7 seronegatives were negative in both PCR assays. The PCR results showed no evidence for a long lag pe riod between infection with HTLV-I and seroconversion. The HTLV-I long terminal repeat (LTR) of these 10 individuals, related in the first t o the fourth degree, was amplified and sequenced. Identical sequences were found within the families except for one woman infected with two variants, one being the familial strain and the other a mutated one wi th a single nucleotide substitution in the 755 sequenced nucleotides o f the LTR region. The family strain and the mutant were both present i n two samples taken 1 year apart. Together, the HTLV-I serology, PCR, and sequencing results point toward mother-to-child transmission as th e main mode of HTLV-I infection in this population. Comparison of the LTR sequences of the two families with other HTLV-I strains from diffe rent geographical regions shows that the Zairean HTLV-I strains form a separate cluster. In contrast to other retroviruses, which have high mutation rates, HTLV-I is genetically very stable as illustrated by th e identical LTR sequences within families and by the small differences between the Zairean strains.