PI3K/Akt/p53 pathway inhibits reovirus infection
| العنوان: | PI3K/Akt/p53 pathway inhibits reovirus infection |
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| المؤلفون: | Xiaozhan Zhang, Liandong Qu, Chunguo Liu, Hongxia Wu, Jin Tian |
| المصدر: | Infection, Genetics and Evolution |
| بيانات النشر: | Elsevier BV, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | p53, Microbiology (medical), p-Akt, phosphorylated Akt, viruses, Orthoreovirus, Mammalian, Replication, Reovirus, Biology, Virus Replication, Microbiology, Article, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, MDM2, Cell Line, Tumor, Genetics, Humans, LY294002, Molecular Biology, Protein kinase B, Ecology, Evolution, Behavior and Systematics, PI3K/AKT/mTOR pathway, PI3K/Akt, Gene knockdown, virus diseases, Nutlin, LY, LY294002, Immunity, Innate, Reoviridae Infections, Cell biology, Infectious Diseases, chemistry, Viral replication, Host-Pathogen Interactions, CHT, α-Chymotrypsin, Cancer research, Wort, Wortmannin, Phosphorylation, Tumor Suppressor Protein p53, Signal transduction, Proto-Oncogene Proteins c-akt, p-MDM2, phosphorylated MDM2, Signal Transduction |
| الوصف: | Highlights • Sero-type 3 reovirus strain MPC/04 transiently activated the PI3K/Akt pathway. • Blockage of PI3K/Akt activation increased viral RNA synthesis and yield. • The downstream effectors MDM2/p53 of PI3K/Akt were activated. • Disturbing MDM2 and p53 cross-talk enhanced reovirus replication. • Overexpression or knockdown of p53 promoted or inhibited reovirus replication. Viral infections activate many host signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which has recently attracted considerable interest due to its central role in modulating virus replication. This study demonstrated that the sero-type 3 reovirus strain Masked Palm Civet/China/2004 (MPC/04) could transiently activate the PI3K/Akt pathway in A549 cells at earlier time points of infection. The blockage of PI3K/Akt activation increased viral RNA synthesis and yield. The role of the downstream effectors MDM2/p53 of PI3K/Akt in regulating reovirus replication was further analyzed. We found that during reovirus infection, the level of phosphorylated MDM2 (p-MDM2) was increased and the expression of p53 was reduced. In addition, the blockage of PI3K/Akt by Ly294002 or knockdown of Akt by siRNA reduced the level of p-MDM2 and increased the level of p53. Both indicated that the downstream effectors MDM2/p53 of PI3K/Akt were activated. Pre-treatment with Nutlin, which can destroy MDM2 and p53 cross-talk and increase the expression of p53 RNA and protein, dose-dependently enhanced reovirus replication. Additionally, the overexpression of p53 alone also supported reovirus replication, and knockdown of p53 significantly inhibited viral replication. This study demonstrates that PI3K/Akt/p53 activated by mammalian reovirus can serve as a pathway for inhibiting virus replication/infection, yet the precise mechanism of this process remains under further investigation. |
| تدمد: | 1567-1348 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d968e2fe98cb4717ee2721af2c64c8fTest https://doi.org/10.1016/j.meegid.2015.06.008Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0d968e2fe98cb4717ee2721af2c64c8f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15671348 |
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