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-3ß (GSK-3ß) 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-3ß 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-3ß expression, resulting in the extended duration of cyclin D1.
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Alt, J.R., Gladden, A.B., and Diehl, J.A. 2002. p21 (Cip1) promotes cyclin D1 nuclear accumulation via direct inhibition of nuclear export. J. Biol. Chem. 277, 8517–8523.
Casanovas, O., Miro, F., Estanyol, J.M., Itarte, E., Agell, N., and Bachs, O. 2000. Osmotic stress regulates the stability of cyclin D1 in a p38SAPK2-dependent manner. J. Biol. Chem. 275, 35091–35097.
Das, S. and Basu, A. 2008. Japanese encephalitis virus infects neural progenitor cells and decreases their proliferation. J. Neurochem. 106, 1624–1636.
DeCaprio, J.A., Ludlow, J.W., Figge, J., Shew, J.Y., Huang, C.M., Lee, W.H., Marsilio, E., Paucha, E., and Livingston, D.M. 1988. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54, 275–283.
Desai, A.S., Chandramuki, A., Gourie-Devi, M., and Ravi, V. 1994. Detection of Japanese encephalitis virus antigens in the CSF using monoclonal antibodies. Clin. Diagn. Virol. 2, 191–199.
Diehl, J.A., Cheng, M., Roussel, M.F., and Sherr, C.J. 1998. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 12, 3499–3511.
Dove, B., Brooks, G., Bicknell, K., Wurm, T., and Hiscox, J.A. 2006. Cell cycle perturbations induced by infection with the corona virus infectious bronchitis virus and their effect on virus replication. J. Virol. 80, 4147–4156.
Eckner, R., Ewen, M.E., Newsome, D., Gerdes, M., DeCaprio, J.A., Lawrence, J.B., and Livingston, D.M. 1994. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev. 8, 869–884.
Fanning, E. and Knippers, R. 1992. Structure and function of simian virus 40 large tumor antigen. Annu. Rev. Biochem. 61, 55–85.
Feuer, R., Mena, I., Pagarigan, R., Slifka, M.K., and Whitton, J.L. 2002. Cell cycle status affects coxsackievirus replication, persistence, and reactivation in vitro. J. Virol. 76, 4430–4440.
Flemington, E.K. 2001. Herpesvirus lytic replication and the cell cycle: arresting new developments. J. Virol. 75, 4475–4481.
Geng, Y., Yu, Q., Sicinska, E., Das, M., Schneider, J.E., Bhattacharya, S., Rideout, W.M., Bronson, R.T., Gardner, H., and Sicinski, P. 2003. Cyclin E ablation in the mouse. Cell 114, 431–443.
Gozlan, J., Lathey, J.L., and Spector, S.A. 1998. Human immunodeficiency virus type 1 induction mediated by genistein is linked to cell cycle arrest in G2. J. Virol. 72, 8174–8180.
He, Y., Xu, K., Keiner, B., Zhou, J., Czudai, V., Li, T., Chen, Z., Liu, J., Klenk, H.D., Shu, Y.L., et al. 2010. Influenza A virus replcation induces cell cycle arrest in G0/G1 phase. J. Virol. 84, 12832–12840.
Howe, J.A., Mymryk, J.S., Egan, C., Branton, P.E., and Bayley, S.T. 1990. Retinoblastoma growth suppressor and a 300-kDa protein appear to regulate cellular DNA synthesis. Proc. Natl. Acad. Sci. USA 87, 5883–5887.
Kannan, R.P., Hensley, L.L., Evers, L.E., Lemon, S.M., and McGivern, D.R. 2011. Hepatitis C virus infection causes cell cycle arrest at the level of initiation of mitosis. J. Virol. 85, 7989–8001.
Kim, K.M., Lee, S.G., Kim, J.M., Kim, D.S., Song, J.Y., Kang, H.L., Lee, W.K., Cho, M.J., Rhee, K.H., Youn, H.S., et al. 2010. Helicobacter pylori γ-glutamyltranspeptidase induces cell cycle arrest at the G1-S phase transition. J. Microbiol. 48, 372–377.
Lim, S. and Kaldis, P. 2013. Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development 140, 3079–3093.
Lin, G.Y. and Lamb, R.A. 2000. The paramyxovirus simian virus 5 V protein slows progression of the cell cycle. J. Virol. 74, 9152–9166.
Lowe, M., Nakamura, N., and Warren, G. 1998. Golgi division and membrane traffic. Trends Cell. Biol. 8, 40–44.
Luo, H., Zhang, J., Dastvan, F., Yanagawa, B., Reidy, M.A., Zhang, H.M., Yang, D., Wilson, J.E., and McManus, B.M. 2003. Ubiquitin-dependent proteolysis of cyclin D1 is associated with Coxsackievirus-induced cell growth arrest. J. Virol. 77, 1–9.
Mathur, A., Arora, K.L., Rawat, S., and Chaturvedi, U.C. 1986. Persistence, latency and reactivation of Japanese encephalitis virus infection in mice. J. Gen. Virol. 67, 381–385.
Nakayama, K. and Nakayama, K. 1998. Cip/Kip cyclin-dependent kinase inhibitors: brakes of the cell cycle engine during development. BioEssays 20, 1020–1029.
Nascimento, R., Costa, H., and Parkhouse, R.M. 2012. Virus manipulation of cell cycle. Protoplasma 249, 519–528.
Obaya, A.J. and Sedivy, J.M. 2002. Regulation of cyclin-Cdk activity in mammalian cells. Cell. Mol. Life Sci. 59, 126–142.
Park, S.Y., Choi, E., and Jeong, Y.S. 2013. Integrative effect of defective interfering RNA accumulation and helper virus attenuation is responsible for the persistent infection of Japanese encephalitis virus in BHK-21 cells. J. Med. Virol. 85, 1990–2000.
Ravi, V., Desai, A.S., Shenoy, P.K., Satishchandra, P., Chandramuki, A., and Gourie-Devi, M. 1993. Persistence of Japanese encephalitis virus in the human nervous system. J. Med. Virol. 40, 326–329.
Rice, D.P., Hodgson, T.A., and Kopstein, A.N. 1985. The economic costs of illness: a replication and update. Health Care Financ. Rev. 7, 61–80.
Satyanarayana, A. and Kaldis, P. 2009. Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 28, 2925–2939.
Schmaljohn, C.S. and Blair, C.D. 1977. Persistent infection of cultured mammalian cells by Japanese encephalitis virus. J. Virol. 24, 580–589.
Schmaljohn, C.S. and Blair, C.D. 1979. Clonal analysis of mammalian cell cultures persistently infected with Japanese encephalitis virus. J. Virol. 31, 816–822.
Sherr, C.J. 1994. G1 phase progression: cycling on cue. Cell 79, 551–555.
Sohn, H., Kim, K., Lee, K.S., Choi, H.G., Lee, K.I., Shin, A.R., Kim, J.S., Shin, S., Song, C.H., Park, J.K., et al. 2014. Lithium inhibits growth of intracellular Mycobacterium kansasii through enhancement of macrophage apoptosis. J. Microbiol. 52, 299–306.
Song, B.H., Yun, G.N., Kim, J.K., Yun, S.I., and Lee, Y.M. 2012. Biological and genetic properties of SA14-14-2, a live-attenuated Japanese encephalitis vaccine that is currently available for humans. J. Microbiol. 50, 698–706.
Stewart, S.A., Poon, B., Jowett, J.B.M., Xie, Y., and Chen, I.S.Y. 1999. Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells. Proc. Natl. Acad. Sci. USA 96, 12039–12043.
Su, H.L., Liao, C.L., and Lin, Y.L. 2002. Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response. J. Virol. 76, 4162–4171.
Umenai, T., Krzysko, R., Bektimirov, T.A., and Assaad, F.A. 1985. Japanese encephalitis: current worldwide status. Bull. World Health Organ. 63, 625–631.
Vaughn, D.W. and Hoke, C.H. Jr. 1992. The epidemiology of Japanese encephalitis: prospects for prevention. Epidem. Rev. 14, 197–221.
Werness, B.A., Levine, A.J., and Howley, P.M. 1990. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248, 76–79.
Yoon, S.W., Lee, S.Y., Won, S.Y., Park, S.H., Park, S.Y., and Jeong, Y.S. 2006. Characterization of homologous defective interfering RNA during persistent infection of Vero cells with Japanese encephalitis virus. Mol. Cell. 21, 112–120.
Yuan, H., Xu, K., Keiner B., Zhou, J., Czudai, V., Li, T., Chen, Z., Liu, J., Klenk, H.D., Shu, Y.L., and Sun, B. 2010. Influenza A virus replication induces cell cycle arrest in G0/G1 phase. J. Virol. 24, 12832–12840.
Yuan, X., Yao, Z., Wu, J., Zhou, Y., Shan, Y., Dong, B., Zhao, Z., Hua, P., Chen, J., and Cong, Y. 2007. G1 phase cell cycle arrest induced by SARS-CoV 3a protein via the cyclin D3/pRb pathway. Am. J. Respir. Cell. Mol. Biol. 37, 9–19.
Zhirnov, O. and Klenk, H.D. 2007. Control of apoptosis in influenza virus-infected cells by up-regulation of Akt and p53 signaling. Apoptosis 12, 1419–1432.
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Kim, J.Y., Park, S.Y., Lyoo, H.R. et al. Extended stability of cyclin D1 contributes to limited cell cycle arrest at G1-phase in BHK-21 cells with Japanese encephalitis virus persistent infection. J Microbiol. 53, 77–83 (2015). https://doi.org/10.1007/s12275-015-4661-z
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DOI: https://doi.org/10.1007/s12275-015-4661-z