Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase

Michael C. Brown, Jeffrey D. Bryant, Elena Y. Dobrikova, Mayya Shveygert, Shelton Bradrick, Vidyalakshmi Chandramohan, Darell D. Bigner, Matthias Gromeier

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Protein synthesis, the most energy-consuming process in cells, responds to changing physiologic priorities, e.g., upon mitogenor stress-induced adaptations signaled through the mitogen-activated protein kinases (MAPKs). The prevailing status of protein synthesis machinery is a viral pathogenesis factor, particularly for plus-strand RNA viruses, where immediate translation of incoming viral RNAs shapes host-virus interactions. In this study, we unraveled signaling pathways centered on the ERK1/2 and p38α MAPK-interacting kinases MNK1/2 and their role in controlling 7-methyl-guanosine (m7G) "cap"-independent translation at enterovirus type 1 internal ribosomal entry sites (IRESs). Activation of Raf-MEK-ERK1/2 signals induced viral IRES-mediated translation in a manner dependent on MNK1/2. This effect was not due to MNK's known functions as eukaryotic initiation factor (eIF) 4G binding partner or eIF4E(S209) kinase. Rather, MNK catalytic activity enabled viral IRES-mediated translation/host cell cytotoxicity through negative regulation of the Ser/Arg (SR)-rich protein kinase (SRPK). Our investigations suggest that SRPK activity is a major determinant of type 1 IRES competency, host cell cytotoxicity, and viral proliferation in infected cells.

Original languageEnglish (US)
Pages (from-to)13135-13148
Number of pages14
JournalJournal of Virology
Volume88
Issue number22
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

guanosine
Guanosine
Mitogen-Activated Protein Kinase Kinases
mitogen-activated protein kinase
protein kinases
Protein Kinases
serine
Serine
translation (genetics)
arginine
Arginine
phosphotransferases (kinases)
cytotoxicity
Eukaryotic Initiation Factor-4G
protein synthesis
process energy
Enterovirus
RNA Viruses
Viral RNA
p38 Mitogen-Activated Protein Kinases

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase. / Brown, Michael C.; Bryant, Jeffrey D.; Dobrikova, Elena Y.; Shveygert, Mayya; Bradrick, Shelton; Chandramohan, Vidyalakshmi; Bigner, Darell D.; Gromeier, Matthias.

In: Journal of Virology, Vol. 88, No. 22, 2014, p. 13135-13148.

Research output: Contribution to journalArticle

Brown, Michael C. ; Bryant, Jeffrey D. ; Dobrikova, Elena Y. ; Shveygert, Mayya ; Bradrick, Shelton ; Chandramohan, Vidyalakshmi ; Bigner, Darell D. ; Gromeier, Matthias. / Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase. In: Journal of Virology. 2014 ; Vol. 88, No. 22. pp. 13135-13148.
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