Phosphatidylinositol-3-kinase-Akt pathway in negative-stranded RNA virus infection: a minireview
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REVIEW
Phosphatidylinositol‑3‑kinase‑Akt pathway in negative‑stranded RNA virus infection: a minireview Javier Blanco1 · Cristina Cameirao1,2 · María Carmen López1 · Isabel Muñoz‑Barroso1 Received: 16 March 2020 / Accepted: 17 June 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract The PI3K/Akt signalling pathway is a crucial signalling cascade that regulates transcription, protein translation, cell growth, proliferation, cell survival, and metabolism. During viral infection, viruses exploit a variety of cellular pathways, including the well-known PI3K/Akt signalling pathway. Conversely, cells rely on this pathway to stimulate an antiviral response. The PI3K/Akt pathway is manipulated by a number of viruses, including DNA and RNA viruses and retroviruses. The aim of this review is to provide up-to-date information about the role of the PI3K-Akt pathway in infection with members of five different families of negative-sense ssRNA viruses. This pathway is hijacked for viral entry, regulation of endocytosis, suppression of premature apoptosis, viral protein expression, and replication. Although less common, the PI3K/Akt pathway can be downregulated as an immunomodulatory strategy or as a mechanism for inducing autophagy. Moreover, the cell activates this pathway as an antiviral strategy for interferon and cytokine production, among other strategies. Here, we present new data concerning the role of this pathway in infection with the paramyxovirus Newcastle disease virus (NDV). Our data seem to indicate that NDV uses the PI3K/Akt pathway to delay cell death and increase cell survival as a means of improving its replication. The interference of negative-sense ssRNA viruses with this essential pathway might have implications for the development of antiviral therapies.
Handling editor: Bert K. Rima.
PHLPP PH domain leucine-rich repeat protein phosphatase PI3K Phosphoinositide 3-kinase PI(3,4)P2=PIP2 Phosphatidylinositol 3,4-bisphosphate PI(3,4,5)P3=PIP3 Phosphatidylinositol 3,4,5-trisphosphate PKB Protein kinase B PP2A Protein phosphatase 2A PTEN Phosphatase and tensin homologue deleted on chromosome 10 SHIP Src homology 2 (SH2)-containing inositol 5-phosphatase ssRNA Single-stranded RNA
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00705-020-04740-1) contains supplementary material, which is available to authorized users.
The PI3K/Akt signalling pathway
Abbreviations BAD Bcl-2-associated death promoter FOXO Forkhead box O1 protein GSK3 Glycogen synthase kinase 3 INPP4B Inositol polyphosphate 4-phosphatase type II mTORC2 Mammalian target of rapamycin complex 2 PDK-1 Phosphoinositide-dependent kinase 1 PH Pleckstrin homology
* Isabel Muñoz‑Barroso [email protected] 1
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Edificio Departamental Lab.106. Plaza Doctores de la Reina s/n, 37007 Salamanca, Spain
Present Address: Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança,
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