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Phosphatidylinositol-3-kinase-Akt pathway in negative-stranded RNA virus infection: a minireview

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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.

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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

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

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Acknowledgements

We thank Dr. Adolfo García-Sastre for providing recombinant rNDV-F3aa-mRFP, NDV, and polyclonal anti-NDV antibodies. We also thank Emma Keck for revising the English.

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  1. Cristina Cameirao

    Present address: Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal

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  1. Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Edificio Departamental Lab.106. Plaza Doctores de la Reina s/n, 37007, Salamanca, Spain

    Javier Blanco, Cristina Cameirao, María Carmen López & Isabel Muñoz-Barroso

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  1. Javier Blanco
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  2. Cristina Cameirao
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Correspondence to Isabel Muñoz-Barroso.

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Blanco, J., Cameirao, C., López, M.C. et al. Phosphatidylinositol-3-kinase-Akt pathway in negative-stranded RNA virus infection: a minireview. Arch Virol 165, 2165–2176 (2020). https://doi.org/10.1007/s00705-020-04740-1

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  • DOI: https://doi.org/10.1007/s00705-020-04740-1

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