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

被引:325
作者
Jeffery, KJM
Usuku, K
Hall, SE
Matsumoto, W
Taylor, GP
Procter, J
Bunce, M
Ogg, GS
Welsh, KI
Weber, JN
Lloyd, AL
Nowak, MA
Nagai, M
Kodama, D
Izumo, S
Osame, M
Bangham, CRM
机构
[1] Univ London Imperial Coll Sci Technol & Med, Sch Med, Dept Immunol, London W2 1PG, England
[2] Univ London Imperial Coll Sci Technol & Med, Sch Med, Dept Genitourinary Med & Communicable dis, London W2 1PG, England
[3] Kagoshima Univ, Fac Med, Dept Med Informat, Kagoshima 8908520, Japan
[4] Kagoshima Univ, Fac Med, Dept Internal Med 3, Kagoshima 8908520, Japan
[5] Kagoshima Univ, Fac Med, Ctr Chron Viral Dis, Div Mol Pathol, Kagoshima 8908520, Japan
[6] Churchill Hosp, Nuffield Dept Surg, Oxford Transplant Ctr, Oxford OX3 7LJ, England
[7] John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England
[8] Univ Oxford, Dept Zool, Oxford OX1 3PS, England
关键词
D O I
10.1073/pnas.96.7.3848
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 ran reduce virus load and so prevent disease in persistent virus infections.
引用
收藏
页码:3848 / 3853
页数:6
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