Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response.
Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response.
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DOI：
10.1084/jem.187.3.341
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发表时间：
1998-02-02
影响因子：
15.3
通讯作者：
Hendricks, RL
中科院分区：
文献类型：
--
作者：
Goldsmith, K;Chen, W;Johnson, DC;Hendricks, RL
单纯疱疹病毒（HSV）感染的细胞蛋白（ICP）47通过抑制与抗原呈递相关的转运蛋白（TAP）来阻断CD 8 + T细胞对感染细胞的识别。在体内，HSV-1在两种不同的组织中复制：在上皮粘膜或表皮中，病毒进入感觉神经元;以及在外周和中枢神经系统中，发生急性和随后的潜伏感染。在这里，我们表明HSV-1 ICP 47 −突变体在小鼠中的神经毒性低于野生型HSV-1，但在上皮组织中复制正常。ICP 47 −突变体的神经毒力降低是由于保护性CD 8 + T细胞反应。与野生型病毒相比，ICP 47 −突变体在免疫正常小鼠和用CD 8 + T细胞重建后的T细胞缺陷裸鼠中表达的神经毒力降低。然而，ICP 47 −突变体在急性耗尽CD 8 + T细胞的小鼠和未重建或用CD 4 + T细胞重建的裸鼠中表现出正常的神经毒力。相比之下，CD 8 + T细胞耗竭并没有增加一种无关的减毒HSV-1糖蛋白（g）E−突变体的神经毒力。ICP 47是第一个显示通过抑制CD 8 + T细胞保护来影响神经毒力的病毒蛋白。
The herpes simplex virus (HSV) infected cell protein (ICP)47 blocks CD8+ T cell recognition of infected cells by inhibiting the transporter associated with antigen presentation (TAP). In vivo, HSV-1 replicates in two distinct tissues: in epithelial mucosa or epidermis, where the virus enters sensory neurons; and in the peripheral and central nervous system, where acute and subsequently latent infections occur. Here, we show that an HSV-1 ICP47− mutant is less neurovirulent than wild-type HSV-1 in mice, but replicates normally in epithelial tissues. The reduced neurovirulence of the ICP47− mutant was due to a protective CD8+ T cell response. When compared with wild-type virus, the ICP47− mutant expressed reduced neurovirulence in immunologically normal mice, and T cell–deficient nude mice after reconstitution with CD8+ T cells. However, the ICP47− mutant exhibited normal neurovirulence in mice that were acutely depleted of CD8+ T cells, and in nude mice that were not reconstituted, or were reconstituted with CD4+ T cells. In contrast, CD8+ T cell depletion did not increase the neurovirulence of an unrelated, attenuated HSV-1 glycoprotein (g)E− mutant. ICP47 is the first viral protein shown to influence neurovirulence by inhibiting CD8+ T cell protection.
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影响因子：
5.4
作者：
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