HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy
HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy
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DOI：
10.1073/pnas.96.7.3848
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发表时间：
1999-03-30
影响因子：
11.1
通讯作者：
Bangham, CRM
中科院分区：
文献类型：
--
作者：
Jeffery, KJM;Usuku, K;Bangham, CRM
与持续性病毒感染相关的疾病风险，如HIV-I、乙型和丙型肝炎B和人类嗜T淋巴细胞病毒-I（HTLV-I），主要由病毒载量决定。然而，目前尚不清楚持续的I类HLA限制性抗病毒细胞毒性T淋巴细胞（CTL）应答是否降低病毒载量并因此有益或导致组织损伤并有助于疾病发病机制。与无症状HTLV-Ⅰ携带者相比，HTLV-Ⅰ相关性脊髓病（HAM/TSP）患者具有较高的病毒载量。我们假设HLA等位基因控制HTLV-Ⅰ前病毒载量，从而影响HAM/TSP的易感性。我们发现，在感染HTLV-I后，I类等位基因HLA-A*02使HAM/TSP的几率减半（P < 0.0001），预防了28%的HAM/TSP潜在病例。此外，HLA-A*02（+）健康HTLV-I携带者的前病毒载量是HLA-A*02（-）HTLV-I携带者的三分之一（P = 0.014）。还鉴定了HLA-DRB 1 *0101与疾病易感性的相关性，这在不存在HLA-A*02的保护作用的情况下使HAM/TSP的几率加倍。这些数据对其他持续性病毒感染具有意义，其中病毒载量与预后相关，并暗示有效的抗病毒CTL应答可以降低病毒载量，从而预防持续性病毒感染中的疾病。
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.