Genetic protection against hepatitis B virus conferred by CCR5Δ32:: Evidence that CCR5 contributes to viral persistence
Genetic protection against hepatitis B virus conferred by CCR5Δ32:: Evidence that CCR5 contributes to viral persistence
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DOI：
10.1128/jvi.01897-06
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Carrington, Mary
中科院分区：
文献类型：
--
作者：
Thio, Chloe L.;Astemborski, Jacquie;Carrington, Mary
从急性B型肝炎病毒（HBV）感染中恢复需要广泛、有力的T细胞应答，当趋化因子受体5（CCR 5）缺失时，这种应答在小鼠中增强。为了检验非功能性CCR 5（CCR 5 Delta 32 [一种含有32 bp缺失的功能无效等位基因]）的产生增加人类从B型肝炎中恢复的可能性的假设，我们研究了来自三个队列的526人，其中一个HBV持续存在的人与两个从HBV感染中恢复的人相匹配。在拉米夫定可用之前确定恢复或持续。我们确定了CCR 5 Delta 32的基因型和CCR 5启动子的多态性以及邻近基因趋化因子受体2（CCR 2）和趋化因子受体样2（CCRL 2）的编码区。应用条件Logistic回归分析比较了190例病毒恢复者和336例病毒持续存在者的等位基因和单倍型频率。CCR 5 Delta 32使发生持续性HBV感染的风险降低近一半（比值比[OR]，0.53; 95%置信区间[CI]，0.33至0.83; P = 0.006）。这种关联在伴有和不伴有人类免疫缺陷病毒感染的人群中几乎相同。在9个缺失纯合子个体中，8个从感染中恢复（OR，0.25; 95%CI，0.03至1.99; P = 0.19）。其他邻近的多态性与HBV结果无关。这些数据证明了CCR 5 Delta 32在从HBV感染中恢复中的保护作用，为CCR 5在对HBV的免疫应答中的作用提供了遗传流行病学证据，并表明了对持续感染HBV的患者的潜在治疗性治疗。
Recovery from acute hepatitis B virus (HBV) infection requires a broad, vigorous T-cell response, which is enhanced in mice when chemokine receptor 5 (CCR5) is missing. To test the hypothesis that production of a nonfunctional CCR5 (CCR5 Delta 32 [a functionally null allele containing a 32-bp deletion]) increases the likelihood of recovery from hepatitis B in humans, we studied 526 persons from three cohorts in which one person with HBV persistence was matched to two persons who recovered from an HBV infection. Recovery or persistence was determined prior to availability of lamivudine. We determined genotypes for CCR5 Delta 32 and for polymorphisms in the CCR5 promoter and in coding regions of the neighboring genes, chemokine receptor 2 (CCR2) and chemokine receptor-like 2 (CCRL2). Allele and haplotype frequencies were compared among the 190 persons with viral recovery and the 336 with persistence by use of conditional logistic regression. CCR5 Delta 32 reduced the risk of developing a persistent HBV infection by nearly half (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.83; P = 0.006). This association was virtually identical in persons with and without a concomitant human immunodeficiency virus infection. Of the nine individuals who were homozygous for the deletion, eight recovered from infection (OR, 0.25; 95% CI, 0.03 to 1.99; P = 0.19). None of the other neighboring polymorphisms examined were associated with HBV outcome. These data demonstrate a protective effect of CCR5 Delta 32 in recovery from an HBV infection, provide genetic epidemiological evidence for a role of CCR5 in the immune response to HBV, and suggest a potential therapeutic treatment for patients persistently infected with HBV.