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

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 strongl y determined by the virus load. However, it is not known whether a persiste nt class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response r educes viral load and is therefore beneficial or causes tissue damage and c ontributes 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 inf luence susceptibility to HAM/TSP. Here we show that, after infection with H TLV-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(+) hea lthy 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 susc eptibility also was identified, which doubled the odds of HAM/TSP in the ab sence of the protective effect of HLA-A*02. These data have implications fo r other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response ran reduce vir us load and so prevent disease in persistent virus infections.