Rotavirus infection induces G1 to S phase transition in MA104 cells via Ca+2/Calmodulin pathway

Abstract

Viruses, obligate cellular parasites rely on host cellular functions and target the host cell cycle for their own benefit. In this study, effect of rotavirus infection on cell cycle machinery was explored. We found that rotavirus (RV) infection in MA104 cells induces the expression of cyclins and cyclin dependent kinases and down-regulates expression of CDK inhibitors, resulting in G1 to S phase transition. The rotavirus induced S phase accumulation was found to be concurrent with induction in expression of calmodulin and activation of CaMKI which is reported as inducer of G1-S phase transition. This cell cycle manipulation was found to be Ca(+2)/Calmodulin pathway dependent. The physiological relevance of G1 to S phase transition was established when viral gene expressions as well as viral titers were found to be increased in S phase synchronized cells and decreased in G0/G1 phase synchronized cells compared to unsynchronized cells during rotavirus infection.

Progressive Rotavirus Infection Downregulates Redox-Sensitive Transcription Factor Nrf2 and Nrf2-Driven Transcription Units

“…The trend of p21 follows the same pattern as that of p53-a decline during the span of 2-8 hours followed by restoration. Regulation of p21, however, was found to be transcriptional and not because of global translational arrest [130]. Concurrent with a previous report of overall activation of transcription factor AP1 [46], a sharp upregulation of c-fos was observed at 6 and 9 hours post RV infection.…”

CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions

“…It suggested that CD38 may induce G1 to S phase transition in cervical cancer cells and contribute to promote cell proliferation rate. The P21‐cyclinD1‐CDK4/6 pathway promotes G1 to S stage transition, and this pathway is commonly dysregulated in a large number of carcinomas . In our study, we found there is a negative relationship between CD38 and P21, and a positive relationship between CD38 and CDK4/cyclinD1 both in vivo and in vitro.…”

“…The P21-cyclinD1-CDK4/6 pathway promotes G1 to S stage transition, and this pathway is commonly dysregulated in a large number of carcinomas. 33 In our study, we found there is a negative relationship between CD38 and P21, and a positive relationship between CD38 and CDK4/cyclinD1 both in vivo and in vitro. We speculated that with the over-expression of CD38, P21 was down-regulated which led to an up-regulation of cyclinD1.…”

Tyrosine phosphorylation modulates mitochondrial chaperonin Hsp60 and delays rotavirus NSP4-mediated apoptotic signaling in host cells

“…Successful infection entails subversion of antiviral immune responses (Graff, Mitzel, Weisend, & Flenniken, ; Barro & Patton, ; Graff, Ettayebi, & Hardy, ), evasion of pre‐mature apoptosis (Bagchi et al, ; Bagchi, Nandi, Nayak, & Chawla‐Sarkar, ; Chanda et al, ), avoidance of stress response (Trujillo‐Alonso, Maruri‐Avidal, Arias, & López, ; Zambrano et al, ) and preferential synthesis of viral proteins and nucleic acids (Groft and Burley, ; Piron, Delaunay, Grosclaude, & Poncet, ; Piron, Vende, Cohen, & Poncet, ; Vende, Piron, Castagné, & Poncet, ), all of which converge to a central strategy employed by viruses‐to usurp host machinery in favor of viral perpetuation. Indeed, heavy reliance of RV multiplication on host protein chaperone system (Dutta et al, ; Dutta et al, ), intracellular calcium metabolism (Chattopadhyay et al, ), intercellular tight junction function (Torres‐Flores, Silva‐Ayala, Espinoza, López, & Arias, ), cell‐cycle machineries (Bhowmick, Banik, Chanda, Chattopadhyay, & Chawla‐Sarkar, ), ubiquitin‐proteasome system (López, Silva‐Ayala, López, & Arias, ), and endocytosis components (Silva‐Ayala et al, ) have been reported.…”