MULTIPLE INDEPENDENT LOCI WITHIN THE HUMAN CYTOMEGALOVIRUS UNIQUE SHORT REGION DOWN-REGULATE EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I HEAVY-CHAINS
MULTIPLE INDEPENDENT LOCI WITHIN THE HUMAN CYTOMEGALOVIRUS UNIQUE SHORT REGION DOWN-REGULATE EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I HEAVY-CHAINS
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DOI：
10.1128/jvi.69.8.4830-4841.1995
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发表时间：
1995-08-01
影响因子：
5.4
通讯作者：
CAMPBELL, AE
中科院分区：
文献类型：
--
作者：
JONES, TR;HANSON, LK;CAMPBELL, AE
主要组织相容性复合物 I 类细胞表面表达的减少发生在腺病毒、单纯疱疹病毒、人巨细胞病毒 (HCMV) 和鼠巨细胞病毒喂养的细胞系统中。最近，已证明由 HCMV 感染介导的下调是翻译后的，这是由于内质网中 I 类重链的周转增加所致（M.F.C.Beersma、M.J.E.Bijlmakers、和 H、L.Ploegh、J.Immunol.151:4455-4464, 1993 ；Y.Yamashita、L Shimokata、S. Saga，S. Mizuno，T. Tsurumi，Y. Nishiyama，J. Virol。 68:7933-7943, 1994。为了鉴定参与 I 类调控的 HCMV 基因，我们筛选了我们的 HCMV 缺失突变体库中的这种表型，该突变体在 HCMV 基因组的 S 部分（包括开放阅读框 IRS1 至 US9 和 US11) 未能下调 I 类重链。通过检查 HCMV 基因组这一部分内较小缺失的影响，发现包含至少 9 个开放阅读框的 7 kb 区域包含减少重链表达所需的基因。此外，确定 7-kb 区域内至少有两个独立基因座能够引起 I 类重链下调。其中之一， US11 编码一种 32 kDa 糖蛋白，在没有其他病毒基因产物的情况下，该糖蛋白会导致 I 类重链下调。因此，与HCMV复制周期表型相关的特定功能已被映射到可有可无的基因区域。这些位点可能对于逃避宿主的免疫反应和病毒持续存在很重要。
Reduction of major histocompatibility complex class I cell surface expression occurs in adenovirus-, herpes simplex virus-, human cytomegalovirus (HCMV)-, and murine cytomegalovirus-infeded cell systems. Recently, it was demonstrated that the down-regulation mediated by HCMV infection is posttranslational, as a result of increased turnover of class I heavy chains in the endoplasmic reticulum (M. F. C. Beersma, M. J. E. Bijlmakers, and H, L. Ploegh, J. Immunol. 151:4455-4464, 1993; Y. Yamashita, L Shimokata, S. Saga, S. Mizuno, T. Tsurumi, and Y. Nishiyama, J. Virol. 68:7933-7943, 1994. To identify HCMV genes involved in class I regulation, we screened our bank of HCMV deletion mutants for this phenotype, A mutant with a 9-kb deletion in the S component of the HCMV genome (including open reading frames IRS1 to US9 and US11) failed to down-regulate class I heavy chains. By examining the effects of smaller deletions within this portion of the HCMV genome, a 7-kb region containing at least nine open reading frames was shown to contain the genes required for reduction in heavy-chain expression. Furthermore, it was determined that at least two independent loci within the 7-kb region were able to cause class I heavy-chain down-regulation. One of these, US11, encodes a 32-kDa glycoprotein which causes down-regulation of class I heavy chains in the absence of other viral gene products. Hence, a specific function associated with a phenotype of the HCMV replicative cycle has been mapped to a dispensable gene region. These loci may be important for evasion of the host's immune response and viral persistence.