Studies on apoptosis induced in the virus-infected cells

为了了解病毒感染动物细胞中病毒诱导细胞凋亡的生物学意义，我们对病毒感染细胞中的细胞凋亡和病毒增殖进行了定量表征。病毒诱导的细胞凋亡是宿主抵抗病毒入侵的一种防御机制。然而，与昆虫病毒感染不同的是，流感病毒和一些RNA动物病毒在感染细胞诱导凋亡的条件下可以快速生长。在感染细胞诱导凋亡时，子代病毒产量达到最高水平，表明流感病毒能够通过快速增殖克服感染细胞的凋亡。另一方面，我们发现HEp-2细胞在用多元醇之一山梨醇处理后立即诱导大量凋亡。通过使用胆固醇处理，我们表明（1）动物病毒能够在凋亡细胞中生长，（2）大DNA病毒，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凋亡，这允许病毒抑制感染细胞中凋亡的诱导，（3）US 3基因是HSV-2抗凋亡基因之一。这些结果表明，细胞凋亡在动物病毒感染中的生物学意义并不在于使感染细胞过早死亡而使病毒增殖失败，而可能是通过将病毒转化为宿主细胞的一种防御机制。感染的细胞对感染动物中巨噬细胞的吞噬活性的靶。

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.