Involvement of multiple epitope-specific cytotoxic T-lymphocyte responses in vaccine-based control of simian immunodeficiency virus replication in rhesus macaques
Involvement of multiple epitope-specific cytotoxic T-lymphocyte responses in vaccine-based control of simian immunodeficiency virus replication in rhesus macaques
复制标题
DOI：
10.1128/jvi.80.4.1949-1958.2006
复制
发表时间：
2006-02-01
影响因子：
5.4
通讯作者：
Matano, T
中科院分区：
文献类型：
--
作者：
Kawada, M;Igarashi, H;Matano, T
细胞毒性T淋巴细胞（CTL）反应是控制免疫缺陷病毒复制的关键。最近在临床前艾滋病疫苗试验中表明，可能参与控制病毒复制的显性单表位特异性CTL，但仍不清楚多个表位特异性CTL是否可以参与基于疫苗的控制。在这里，通过随访5只猕猴，显示基于疫苗的控制的猴免疫缺陷病毒，SlVmac239的初级复制，我们提出的证据表明参与多个表位特异性CTL反应在此控制。三只猕猴保持控制超过2年，而没有额外的前病毒突变。然而，在其他两个共享的主要组织相容性复合体单倍型，病毒突变积累在一个类似的顺序，导致病毒逃避三个表位特异性CTL反应与病毒健身成本。这些多重逃逸突变的积累导致在攻毒后约60周再次出现血浆病毒血症。我们的研究结果涉及多个表位特异性CTL反应在控制免疫缺陷病毒复制，并进一步表明，连续积累的多个CTL逃逸突变，如果允许的话，可以导致病毒逃避这种控制。
Cytotoxic T-lymphocyte (CTL) responses are crucial for the control of immunodeficiency virus replication. Possible involvement of a dominant single epitope-specific CTL in control of viral replication has recently been indicated in preclinical AIDS vaccine trials, but it has remained unclear if multiple epitope-specific CTLs can be involved in the vaccine-based control. Here, by following up five rhesus macaques that showed vaccine-based control of primary replication of a simian immunodeficiency virus, SlVmac239, we present evidence indicating involvement of multiple epitope-specific CTL responses in this control. Three macaques maintained control for more than 2 years without additional mutations in the provirus. However, in the other two that shared a major histocompatibility complex haplotype, viral mutations were accumulated in a similar order, leading to viral evasion from three epitope-specific CTL responses with viral fitness costs. Accumulation of these multiple escape mutations resulted in the reappearance of plasma viremia around week 60 after challenge. Our results implicate multiple epitope-specific CTL responses in control of immunodeficiency virus replication and furthermore suggest that sequential accumulation of multiple CTL escape mutations, if allowed, can result in viral evasion from this control.