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

Studies on apoptosis induced in the virus-infected cells

病毒感染细胞诱导细胞凋亡的研究

基本信息

批准号：
11670298
负责人：
KOYAMA Hajime
金额：
$ 1.86万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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/grant/KAKENHI-PROJECT-11670298/
关键词：
apoptosis antiapoptosis sorbitol virus phagocytosis defense mechanism 抗ウイルス作用

项目摘要

To understand the biological significance of virus-induced apoptosis in animal virus infection, we quantitatively characterized apoptosis and virus multiplication in the virus-infected cells. Based on the observation that the multiplication of the insect virus was abolished when the infected cells induced apoptosis, virus-induced apoptosis has been considered to be one of the host defense mechanism against virus invasion. However, in contrast to the infection with insect viruses, influenza virus and some RNA animal viruses can grow rapidly under the conditions that the infected cells induced apoptosis. The progeny virus yield reached the maximum level at the time when these infected cells induced apoptosis, indicating influenza virus is able to overcome apoptosis of the infected cells by a rapid multiplication.On the other hand, we found that HEp-2 cells induced massive apoptosis immediately after the treatment with sorbitol, one of the polyhydric alcohol. By the use of sorbitol-treatment, we showed that (1) animal viruses are able to grow in the apoptotic cells, (2) large DNA viruses, such as herpes simplex virus type one (HSV-1) and type 2 (HSV-2), overcome apoptosis by multiple antiapoptosis genes of the viruses which allow the viruses to suppress the induction of apoptosis in the infected cells, and (3) one of antiapoptosis genes of HSV-2 is US3 gene.These results indicate that the biological significance of apoptosis in the animal virus infection is not the abortion of virus multiplication by premature death of the infected cells and suggest that apoptosis works as a host defense mechanism by converting the virus-infected cells to the target of phagocytotic activity of macrophages in the infected animal.

为了了解动物病毒感染中病毒诱导细胞凋亡的生物学意义，我们定量表征了病毒感染细胞中的细胞凋亡和病毒增殖。基于当受感染的细胞诱导细胞凋亡时昆虫病毒的增殖被终止的观察，病毒诱导的细胞凋亡被认为是宿主抵抗病毒入侵的防御机制之一。然而，与昆虫病毒的感染不同，流感病毒和一些RNA动物病毒在被感染细胞诱导凋亡的条件下可以快速生长。当这些感染细胞诱导细胞凋亡时，子代病毒产量达到最高水平，这表明流感病毒能够通过快速增殖来克服感染细胞的凋亡。另一方面，我们发现HEp-2细胞在用山梨醇（一种多元醇）处理后立即诱导大量细胞凋亡。通过使用山梨醇处理，我们表明（1）动物病毒能够在凋亡细胞中生长，（2）大型DNA病毒，例如单纯疱疹病毒1型（HSV-1）和2型（HSV-2），通过病毒的多个抗凋亡基因克服细胞凋亡，使病毒能够抑制感染细胞中细胞凋亡的诱导，以及（3）其中一种 HSV-2的抗凋亡基因是US3基因。这些结果表明，动物病毒感染中细胞凋亡的生物学意义并不在于受感染细胞过早死亡而导致病毒增殖的中止，并且表明细胞凋亡通过将病毒感染的细胞转变为受感染动物中巨噬细胞吞噬活性的目标而发挥宿主防御机制的作用。