Virus escape from CTL recognition.
Virus escape from CTL recognition.
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DOI：
10.1084/jem.180.3.779
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发表时间：
1994-09-01
期刊：
影响因子：
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通讯作者：
Koup RA
中科院分区：
文献类型：
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作者：
Koup RA
C类MHC限制性细胞毒性T淋巴细胞(CTL)在体外和体内都有很强的抗病毒活性(1-3)。因此，病毒进化出复杂的机制来逃避CTL的影响就不足为奇了。几乎按照定义，持久性病毒是一种进化出某种机制以避免宿主CTL反应的病毒。在大多数持续的病毒感染中，逃避CTL会导致宿主的终生感染，少数人会因病毒感染而遭受病理后果(4)。然而，在艾滋病毒感染中，病毒的持久性和感染的破坏性后果都是规则，而不是例外。假设逃离CTL在HIV维持持续感染的能力中起作用，那么更好地理解这一现象和这种病毒具体采用的机制就变得至关重要。在本期杂志中，Coulin等人对HIV如何通过基因变异逃避CTL识别提供了洞察力。一些证据表明，CTL是对艾滋病毒感染的保护性免疫反应的重要组成部分。HIV特异性CTL前体在感染早期出现的频率很高，通常在血清转换之前就可以检测到(6)。在随后延长的感染无症状阶段，在没有体外刺激的情况下，HIV特异性CD8+MHC I类限制性CTL活性通常可以直接从外周血中检测到(7，8)。极限稀释分析证实，这些患者的外周血中存在高频率的激活和记忆HIV特异性CTL(9-11)。然而，尽管有这种强有力的CTL反应，病毒仍在继续复制(12，13)。进展为艾滋病的特点是病毒复制增加，伴随着CD8+HIV特异性CTL反应的丧失(11，14)。CTL反应与最初的病毒血症的急剧下降以及随后的病毒血症控制的丧失和进展到艾滋病之间的联系强烈地涉及到在感染的无症状阶段控制HIV复制的CTL反应。那么，HIV或任何其他持久性病毒如何逃避宿主的CTL反应？在第一次检查时，人们可能会认为，通过改变CTL反应识别的表位(S)内的氨基酸序列，病毒就能逃脱CTL反应。虽然这可能是最深入的研究，但它绝不是唯一或最常用的病毒逃逸机制。表1列出了病毒用来避免主机CTL响应的已定义和建议的机制。这篇评论将会
C lass I MHC-restricted cytotoxic T lymphocytes (CTL) have been demonstrated to have potent antiviral activity both in vitro and in vivo (1-3). It is therefore not surprising that viruses have evolved sophisticated mechanisms to escape the effects of CTL. Almost by definition, a persistent virus is one that has evolved some mechanism for avoiding the CTL response of the host. In most persistent virus infections, escape from CTL results in life-long infection of the host with some small fraction of the population suffering pathologic consequences from the virus infection (4). In HIV infection, however, both viral persistence and the devastating consequences of that infection are the rule, rather than the exception. Assuming that escape from CTL plays a role in the ability of HIV to maintain persistent infection, it becomes imperative to better understand this phenomenon and the mechanisms specifically employed by this virus. In this issue of the Journal, Couillin et al.(5) provide insight into how HIV may escape CTL recognition through genetic variation. Several lines of evidence suggest that CTL are an important component of the protective immune response to HIV infection. HIV-specific CTL precursors are present at high frequency very early during infection, often being detectable before seroconversion (6). During the subsequent prolonged asymptomatic phase of infection, HIV-specific CD8+ MHC class I-restricted CTL activity can routinely be detected directly from the peripheral blood in the absence of in vitro stimulation (7, 8). Limiting dilution analysis has confirmed that a high frequency of activated and memory HIV-specific CTL are present in the peripheral blood of these patients (9-11). However, despite this vigorous CTL response, the virus continues to replicate (12, 13). Progression to AIDS is marked by an increase in virus replication accompanied by a loss of the CD8+ HIV-specific CTL response (11, 14). The association of the CTL response with the initial, acute decrease in viremia and the subsequent loss of that control with progression to AIDS strongly implicates the CTL response in control of HIV replication during the asymptomatic phase of infection.How then might HIV, or any other persistent virus, evade the CTL response of the host? On first inspection one might assume that a virus would simply escape a CTL response by altering the amino acid sequence within the epitope (s) recognized by that response. While this may be the most intensively studied, it is by no means the only, or the most frequently used, viral escape mechanism. Table 1 provides a listing of defined and proposed mechanisms utilized by viruses to avoid the CTL response of the host. This commentary will