HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy

TLDR

The risk of disease from persistent viruses such as HTLV‑I is strongly linked to viral load, and HAM/TSP patients exhibit higher loads than asymptomatic carriers. The study aims to determine whether HLA alleles modulate HTLV‑I proviral load and thereby affect susceptibility to HAM/TSP. HLA‑A*02 reduces HAM/TSP risk by 50 % and lowers proviral load to one‑third, while HLA‑DRB1*0101 increases risk, indicating that efficient CTL responses can lower viral load and prevent disease.

Abstract

The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM/TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus influence susceptibility to HAM/TSP. Here we show that, after infection with HTLV-I, the class I allele HLA - A*02 halves the odds of HAM/TSP ( P < 0.0001), preventing 28% of potential cases of HAM/TSP. Furthermore, HLA-A*02 + healthy HTLV-I carriers have a proviral load one-third that ( P = 0.014) of HLA - A*02 − HTLV-I carriers. An association of HLA - DRB1*0101 with disease susceptibility also was identified, which doubled the odds of HAM/TSP in the absence of the protective effect of HLA-A*02. These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.