权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of Epstein-Barr virus-encoded latent membrane protein 2A on maintenance of latent infection

EB病毒编码的潜伏膜蛋白2A在维持潜伏感染中的作用

基本信息

批准号：
11470073
负责人：
TAKADA Kenzo
金额：
$ 10.11万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470073/
关键词：
Epstein-Barr virus LMP2A latent infection membrane immunoglobulin 活性化カルシウム動員

项目摘要

To quantitatively evaluate the role of Epstein-Barr virus (EBV)-encoded latent membrane protein 2A(LMP2A) in immortalization of peripheral B-lymphocytes, we used the Akata cell system to generate an EBV recombinant in which the first exon of the LMP2A gene was disrupted. The results indicated that deletion of the LMP2A gene did not affect the immortalization efficiency of EBV in B-lymphocytes. Deletion of the LMP2A gene made EBV-transformed lymphocytes more permissive for virus replication in response to surface immunoglobulin cross-linking. On the other hand Akata cells, in which LMP2A expression was much lower than in EBV-transformed lymphocytes, were equally permissive for virus replication whether they were infected with wild EBV or LMP2A-knockout EBV. The results raise a question as to the role of LMP2A in inhibition of disruption of virus latency in vivo, where LMP2A expression has been expected to be low as in Akata cells. Furthermore, to clarify the strain variation of the LMP2A gene, we determined the nucleotide sequence of the LMP2A gene of Akata strain and compared it with that of B95-8 strain. Three nucleotide differences were found between Akata and B95-8 strains, which resulted in three amino acid changes, but the two ITAM motifs that were important for blocking signal transduction through crosslinking of B-cell surface immunoglobulins were conserved in two EBV strains. These results suggest that the LMP2A genes of both viruses are not functionally different.

为了定量评价EB病毒（EBV）编码的潜伏膜蛋白2A（LMP 2A）在外周血B淋巴细胞永生化中的作用，我们使用Akata细胞系统产生EBV重组体，其中LMP 2A基因的第一个外显子被破坏。结果表明，LMP 2A基因的缺失并不影响EB病毒在B淋巴细胞中的永生化效率。LMP 2A基因的缺失使得EBV转化的淋巴细胞更容易响应于表面免疫球蛋白交联而进行病毒复制。另一方面，Akata细胞中LMP 2A的表达比EBV转化的淋巴细胞低得多，无论它们被野生型EBV还是LMP 2A敲除的EBV感染，它们都同样允许病毒复制。该结果提出了一个关于LMP 2A在体内抑制病毒潜伏期破坏中的作用的问题，其中LMP 2A表达预期与Akata细胞中一样低。此外，为了阐明LMP 2A基因的菌株变异，我们测定了Akata株LMP 2A基因的核苷酸序列，并与B 95 -8株进行了比较。Akata和B 95 -8株之间发现三个核苷酸差异，这导致三个氨基酸的变化，但两个ITAM基序，这是重要的阻断信号转导通过交联的B细胞表面免疫球蛋白是保守的两个EBV株。这些结果表明，两种病毒的LMP 2A基因在功能上没有差异。