Title |
Extended stability of cyclin D1 contributes to limited cell cycle arrest at G1-phase in BHK-21 cells with Japanese encephalitis virus persistent infection |
Author |
Ji Young Kim, Soo Young Park, Hey Rhyoung Lyoo, Eung Seo Koo, Man Su Kim, and Yong Seok Jeong* |
Address |
Department of Biology and Research Institute of Basic Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea |
Bibliography |
Journal of Microbiology, 53(1),77-83, 2015,
|
DOI |
10.1007/s12275-015-4661-z
|
Key Words |
Japanese encephalitis virus, persistent infection,
cell cycle, cyclin D1, GSK-3β |
Abstract |
There is increasing evidence that many RNA viruses manipulate
cell cycle control to achieve favorable cellular environments
for their efficient replication during infection. Although
virus-induced G0/G1 arrest often delays early apoptosis temporarily,
a prolonged replication of the infected virus leads
host cells to eventual death. In contrast, most mammalian
cells with RNA virus persistent infection often escape cytolysis
in the presence of productive viral replication. In this study,
we demonstrated that the extended endurance of cyclin D1
was clearly associated with the suppression of glycogen synthase
kinase-3β (GSK-3β) expression in BHK-21 cells that are
persistently infected with Japanese encephalitis virus (JEV).
The G0/G1 arrest of these cells turned much loose compared
to the normal BHK-21 cells with JEV acute infection. After
cycloheximide treatment, cyclin D1 in the persistently infected
cells lasted several hours longer than those in acutely
infected cells. Furthermore, both p21Cip1 and p27Kip1, positive
regulators for cyclin D1 accumulation in the nucleus, were
suppressed in their expression, which contrasts with those
in JEV acute infection. Inhibition of the GSK-3β by lithium
chloride treatment rescued a significant number of cells from
cytolysis in JEV acute infection, which coincided with the
levels of cyclin D1 that escaped from proteolysis. Therefore,
the limitation of G1/S arrest in the BHK-21 cells with JEV persistent
infection is associated with the suppression of GSK-3β
expression, resulting in the extended duration of cyclin D1. |