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RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3\u03b2 were detected from 24\u201396 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production.<\/jats:p>","DOI":"10.1186\/1743-422x-2-1","type":"journal-article","created":{"date-parts":[[2005,1,12]],"date-time":"2005-01-12T20:28:42Z","timestamp":1105561722000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["The involvement of survival signaling pathways in rubella-virus induced apoptosis"],"prefix":"10.1186","volume":"2","author":[{"given":"Samantha","family":"Cooray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M","family":"Best","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,1,4]]},"reference":[{"key":"16_CR1","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1007\/s007050050150","volume":"142","author":"KV Pugachev","year":"1997","unstructured":"Pugachev KV, Abernathy ES, Frey TK: Genomic sequence of the RA27\/3 vaccine strain of rubella virus.\n                           Arch Virol 1997, 142: 1165-1180. 10.1007\/s007050050150","journal-title":"Arch Virol"},{"key":"16_CR2","doi-asserted-by":"publisher","first-page":"5133","DOI":"10.1128\/JVI.74.11.5133-5141.2000","volume":"74","author":"Y Liang","year":"2000","unstructured":"Liang Y, Gillam S: Mutational analysis of the rubella virus nonstructural polyprotein and its cleavage products in virus replication and RNA synthesis.\n                           J Virol 2000, 74: 5133-5141. 10.1128\/JVI.74.11.5133-5141.2000","journal-title":"J Virol"},{"key":"16_CR3","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0065-3527(08)60328-0","volume":"44","author":"TK Frey","year":"1994","unstructured":"Frey TK: Molecular biology of rubella virus.\n                           Adv Virus Res 1994, 44: 69-160.","journal-title":"Adv Virus Res"},{"key":"16_CR4","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1006\/viro.1998.9179","volume":"246","author":"J Yao","year":"1998","unstructured":"Yao J, Yang D, Chong P, Hwang D, Liang Y, Gillam S: Proteolytic processing of rubella virus nonstructural proteins.\n                           Virology 1998, 246: 74-82. 10.1006\/viro.1998.9179","journal-title":"Virology"},{"key":"16_CR5","first-page":"387","volume-title":"Principles and practice of clinical virology","author":"JM Best","year":"2000","unstructured":"Best JM, Banatvala JE: Rubella. 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