Selective transmission of R5 HIV-1 variants: where is the gatekeeper?
Selective transmission of R5 HIV-1 variants: where is the gatekeeper?
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DOI：
10.1186/1479-5876-9-s1-s6
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发表时间：
2011-01-27
影响因子：
7.4
通讯作者：
Margolis LB
中科院分区：
文献类型：
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作者：
Grivel JC;Shattock RJ;Margolis LB
为了进入靶细胞，HIV-1使用了CD4和一个辅助受体。在体内，共受体功能由CCR5(针对R5)或CXCR4(针对X4HIV-1)提供。虽然R5和X4 HIV-1变种都存在于体液(精液、血液、宫颈阴道和直肠分泌物)中，但R5 HIV-1似乎传播感染，并在HIV疾病的早期阶段占据主导地位。此外，最近对急性感染病毒的序列分析表明，在大多数传播病例中，感染是由单一病毒发起的。因此，有人建议存在一个“看门人”，它选择R5而不是X4 HIV-1，并在R5 HIV-1变种之间操作。在本次审查中，我们考虑了艾滋病毒传播的各种途径，并讨论了与每一种途径相关的潜在把关机制。虽然已经确定了许多机制，但没有一种机制解释了在HIV-1传播中，R5而不是X4几乎是完美的选择。我们建议，不是只有一个强大的看门人，而是有多个功能的看门人，它们的叠加足以预防X4HIV-1感染，并有可能在R5HIV-1变种中进行选择。综上所述，我们认为多障碍原理更具一般性，不限于对X4HIV-1的保护，而是可以应用于当一个因素具有选择性优势时的其他现象(S)。在HIV-1传播的把关人的情况下，任务是识别他们并破译他们的分子机制。了解守门人的本地化和功能可能使我们能够加强现有的针对R5传播的屏障，并建立针对所有HIV-1变种的新屏障。
To enter target cells HIV-1 uses CD4 and a coreceptor. In vivo the coreceptor function is provided either by CCR5 (for R5) or CXCR4 (for X4 HIV-1). Although both R5 and X4 HIV-1 variants are present in body fluids (semen, blood, cervicovaginal and rectal secretions), R5 HIV-1 appears to transmit infection and dominates early stages of HIV disease. Moreover, recent sequence analysis of virus in acute infection shows that, in the majority of cases of transmission, infection is initiated by a single virus. Therefore, the existence of a “gatekeeper” that selects R5 over X4 HIV-1 and that operates among R5 HIV-1 variants has been suggested. In the present review we consider various routes of HIV-transmission and discuss potential gatekeeping mechanisms associated with each of these routes. Although many mechanisms have been identified none of them explains the almost perfect selection of R5 over X4 in HIV-1 transmission. We suggest that instead of one strong gatekeeper there are multiple functional gatekeepers and that their superimposition is sufficient to protect against X4 HIV-1 infection and potentially select among R5 HIV-1 variants. In conclusion, we propose that the principle of multiple barriers is more general and not restricted to protection against X4 HIV-1 but rather can be applied to other phenomena when one factor has a selective advantage over the other(s). In the case of gatekeepers for HIV-1 transmission, the task is to identify them and to decipher their molecular mechanisms. Knowledge of the gatekeepers‘ localization and function may enable us to enhance existing barriers against R5 transmission and to erect the new ones against all HIV-1 variants.