Familial Transmission and Minimal Sequence Variability of Human T-Lymphotropic Virus Type I (HTLV-I) in Zaire

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Abstract
Our group previously reported a strong familial clustering of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Zaire, suggesting a familial transmission of the virus together with the presence 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 children had a seropositive mother and that all 15 children with a seropositive father but a seronegative mother were seronegative. Lymphocytes of 17 relatives from 2 families with a familial HTLV-I-associated neuropathy were tested in 2 polymerase chain reaction (PCR) assays amplifying 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 period between infection with HTLV-I and seroconversion. The HTLV-I long terminal repeat (LTR) of these 10 individuals, related in the first to 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 with a single nucleotide substitution in the 755 sequenced nucleotides of the LTR region. The family strain and the mutant were both present in two samples taken 1 year apart. Together, the HTLV-I serology, PCR, and sequencing results point toward mother-to-child transmission as the main mode of HTLV-I infection in this population. Comparison of the LTR sequences of the two families with other HTLV-I strains from different 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 the identical LTR sequences within families and by the small differences between the Zairean strains.

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