The Multiple Immune-Evasion Genes of Murine Cytomegalovirus Are Not Redundant
The Multiple Immune-Evasion Genes of Murine Cytomegalovirus Are Not Redundant
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鼠巨细胞病毒的多个免疫逃避基因并非冗余
DOI：
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发表时间：
2001
影响因子：
15.3
通讯作者：
A. Hill
中科院分区：
文献类型：
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作者：
D. Kavanagh;Marielle C. Gold;M. Wagner;U. Koszinowski;A. Hill
人类巨细胞病毒 (HCMV) 和鼠巨细胞病毒 (MCMV) 均编码多个基因，这些基因可干扰 I 类主要组织相容性复合体 (MHC) 的抗原呈递，从而保护感染目标免遭病毒特异性细胞毒性 T 淋巴细胞 (CTL) 裂解。 HCMV 已被证明编码四个这样的基因，MCMV 编码两个。 MCMV m152 阻断 I 类从前高尔基体区室的输出，MCMV m6 将 I 类引导至溶酶体进行降解。第三个 MCMV 基因 m4 编码一种与 I 类相关的在细胞表面表达的糖蛋白。在这里，我们表明 m4 是一种 CTL 逃避基因，与之前描述的免疫逃避基因不同，它抑制 CTL 而不阻断 I 类表面表达。 m152 是阻断抗原呈递给 Kb 和 Db 限制性 CTL 克隆所必需的，而 m4 则是阻断抗原呈递给 Kb 限制性克隆所必需的。 m152 导致 Db 完全保留在前高尔基体隔室中，但仅部分保留 Kb。因此，虽然 m152 有效抑制 Db 限制性 CTL，但需要 m4 才能完全抑制 Kb 限制性 CTL。我们认为巨细胞病毒编码多个免疫逃避基因，以应对远交宿主群体中 I 类分子的多样性。
Both human cytomegaloviruses (HCMVs) and murine cytomegaloviruses (MCMVs) encode multiple genes that interfere with antigen presentation by major histocompatibility complex (MHC) class I, and thus protect infected targets from lysis by virus-specific cytotoxic T lymphocytes (CTLs). HCMV has been shown to encode four such genes and MCMV to encode two. MCMV m152 blocks the export of class I from a pre-Golgi compartment, and MCMV m6 directs class I to the lysosome for degradation. A third MCMV gene, m4, encodes a glycoprotein which is expressed at the cell surface in association with class I. Here we here show that m4 is a CTL-evasion gene which, unlike previously described immune-evasion genes, inhibited CTLs without blocking class I surface expression. m152 was necessary to block antigen presentation to both Kb- and Db-restricted CTL clones, while m4 was necessary to block presentation only to Kb-restricted clones. m152 caused complete retention of Db, but only partial retention of Kb, in a pre-Golgi compartment. Thus, while m152 effectively inhibited Db-restricted CTLs, m4 was required to completely inhibit Kb-restricted CTLs. We propose that cytomegaloviruses encode multiple immune-evasion genes in order to cope with the diversity of class I molecules in outbred host populations.
DOI：
10.1073/pnas.93.21.11327
发表时间：
1996-10-15
影响因子：
11.1
作者：
Jones, TR;Wiertz, EJHJ;Ploegh, HL
通讯作者：
Ploegh, HL