Role of Human TRIM5α in Intrinsic Immunity.
Role of Human TRIM5α in Intrinsic Immunity.
复制标题
人类 TRIM5α 在内在免疫中的作用。
DOI：
10.3389/fmicb.2012.00097
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发表时间：
2012
影响因子：
5.2
通讯作者：
Shioda T
中科院分区：
文献类型：
--
作者：
Nakayama EE;Shioda T
人类免疫缺陷病毒（HIV）的宿主范围非常狭窄。HIV-1不会感染旧大陆的猴子，如恒河猴（Rh）。Rh TRIM 5 α被鉴定为赋予对HIV-1感染的抗性、内在免疫的因子。不幸的是，人类TRIM 5 α几乎无法限制HIV-1。然而，人TRIM 5 α有效限制N嗜性鼠白血病病毒（MLV），但不限制B嗜性MLV，表明人TRIM 5 α代表先前指定为Ref 1的限制因子。非洲绿色猴TRIM 5 α代表另一种限制因子，以前称为Lv 1，它限制HIV-1和从猕猴（SIVmac）感染中分离的猿猴免疫缺陷病毒。TRIM 5是包含RING、B-box 2和卷曲螺旋结构域的三重基序家族的成员。RING结构域通常存在于E3泛素连接酶中，TRIM 5 α被认为通过泛素-蛋白酶体依赖性和非依赖性途径降解病毒核心。TRIM 5的α同种型具有额外的C末端PRYSPRY结构域，其是TRIM 5 α的物种特异性逆转录病毒限制的决定因素。另一方面，病毒衣壳蛋白（CA）的靶区域分散在核心的表面。HIV-2 CA的α-螺旋6和7（L 6/7）之间的表面暴露环中的单个氨基酸差异会影响病毒对人TRIM 5 α的敏感性，并且还显示与西非HIV-2患者的病毒载量相关，表明人TRIM 5 α是体内HIV-2复制的关键调节剂。有趣的是，CA的L 6/7对应于MLV对小鼠因子FV 1敏感性的决定因素，其有效地限制了N-嗜性MLV。此外，人类基因多态性也影响人TRIM 5 α的抗病毒活性。最近，人TRIM 5 α被证明通过与TAK 1复合物相互作用而激活导致NF-κB和AP-1活化的信号通路。因此，TRIM 5 α以多种方式参与控制病毒感染。
Human immunodeficiency virus (HIV) has a very narrow host range. HIV type 1 (HIV-1) does not infect Old World monkeys, such as the rhesus monkey (Rh). Rh TRIM5α was identified as a factor that confers resistance, intrinsic immunity, to HIV-1 infection. Unfortunately, human TRIM5α is almost powerless to restrict HIV-1. However, human TRIM5α potently restricts N-tropic murine leukemia viruses (MLV) but not B-tropic MLV, indicating that human TRIM5α represents the restriction factor previously designated as Ref1. African green monkey TRIM5α represents another restriction factor previously designated as Lv1, which restricts both HIV-1 and simian immunodeficiency virus isolated from macaque (SIVmac) infection. TRIM5 is a member of the tripartite motif family containing RING, B-box2, and coiled-coil domains. The RING domain is frequently found in E3 ubiquitin ligase, and TRIM5α is thought to degrade viral core via ubiquitin–proteasome-dependent and -independent pathways. The alpha isoform of TRIM5 has an additional C-terminal PRYSPRY domain, which is a determinant of species-specific retrovirus restriction by TRIM5α. On the other hand, the target regions of viral capsid protein (CA) are scattered on the surface of core. A single amino acid difference in the surface-exposed loop between α-helices 6 and 7 (L6/7) of HIV type 2 (HIV-2) CA affects viral sensitivity to human TRIM5α and was also shown to be associated with viral load in West African HIV-2 patients, indicating that human TRIM5α is a critical modulator of HIV-2 replication in vivo. Interestingly, L6/7 of CA corresponds to the MLV determinant of sensitivity to mouse factor Fv1, which potently restricts N-tropic MLV. In addition, human genetic polymorphisms also affect antiviral activity of human TRIM5α. Recently, human TRIM5α was shown to activate signaling pathways that lead to activation of NF-κB and AP-1 by interacting with TAK1 complex. TRIM5α is thus involved in control of viral infection in multiple ways.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1013426108
发表时间：
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DOI：
10.1016/j.bbrc.2005.10.173
发表时间：
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影响因子：
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通讯作者：
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