Transient activation of the PI3K/Akt pathway promotes Newcastle disease virus replication and enhances anti-apoptotic signaling responses
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Yinfeng Kang1,2,3, Runyu Yuan1,3,4, Xiaqiong Zhao1,3, Bin Xiang1,3, Shimin Gao5, Pei Gao1,3, Xu Dai1,3, Minsha Feng1,3, Yanling Li1,3, Peng Xie1,3, Yulian Li1,3, Xiaoyi Gao1,3, Tao Ren1,3
1Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China
2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
3Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou, 510642, China
4Key Laboratory for Repository and Application of Pathogenic Microbiology, Research Center for Pathogens Detection Technology of Emerging Infectious Diseases, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 510300, China
5College of Animal Science and Technology, Shanxi Agricultural University, Jinzhong, 030800, China
Yinfeng Kang, email: [email protected]
Tao Ren, email: [email protected]
Keywords: Newcastle disease virus, PI3K/Akt, replication, apoptosis, cell survival
Received: November 01, 2016 Accepted: February 06, 2017 Published: March 01, 2017
Viral infection activates a host’s cellular phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which is involved in cell differentiation, growth, survival, and apoptosis. To elucidate molecular mechanisms in the pathogenesis of Newcastle disease virus (NDV), we demonstrated that NDV transiently activates the PI3K/Akt pathway in chicken cells at an early phase of infection. Its activation was observed as early as 15 min post-infection and gradually weakened after 24 h. Incubating cells with a PI3K inhibitor, LY294002 or wortmannin, prior to NDV infection decreased NDV progeny yields and suppressed Akt phosphorylation at early times post-infection. Akt activation is triggered by NDV-GM or NDV-F48E9 and is abolished by methyl β-cyclodextrin and chlorpromazine. Treatment following NDV-La Sota infection had no obvious effect. However, inhibiting PI3K activation promoted apoptotic responses during an early stage of NDV infection. The pan caspase inhibitor ZVAD-FMK mitigated the reduction in Akt phosphorylation by inhibiting PI3K activation, which indicates the signaling pathway promotes cell survival and, in turn, facilitates viral replication. By suppressing premature apoptosis upon NDV infection, the PI3K/Akt pathway enhances the anti-apoptotic response.
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