Catalog Home Page

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

Jeffery, K.J.M., Usuku, K., Hall, S.E., Matsumoto, W., Taylor, G.P., Procter, J., Bunce, M., Ogg, G.S., Welsh, K.I., Weber, J.N., Lloyd, A.L., Nowak, M.A., Nagai, M., Kodama, D., Izumo, S., Osame, M. and Bangham, C.R.M. (1999) HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. Proceedings of the National Academy of Sciences, 96 (7). pp. 3848-3853.

[img]
Preview
PDF - Published Version
Download (102kB) | Preview
    Link to Published Version: http://dx.doi.org/10.1073/pnas.96.7.3848
    *Subscription may be required

    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.

    Publication Type: Journal Article
    Publisher: National Academy of Sciences
    URI: http://researchrepository.murdoch.edu.au/id/eprint/5685
    Item Control Page

    Downloads

    Downloads per month over past year