Oct 28, 2018

SV40 polyomavirus activates the Ras-MAPK signaling pathway for vacuolization, cell death, and virus release

BioRxiv : the Preprint Server for Biology
Nasim MotamediDaniel DiMaio

Abstract

Polyomaviruses are a family of small, non-enveloped DNA viruses that can cause severe disease in immunosuppressed individuals. Studies with SV40, a well-studied model polyomavirus, have revealed the role of host proteins in polyomavirus entry and trafficking to the nucleus, viral transcription and DNA replication, and cell transformation. In contrast, little is known about host factors or cellular signaling pathways involved in the late steps of productive infection leading to polyomavirus release. We previously showed that cytoplasmic vacuolization, a characteristic late cytopathic effect of SV40, depends on the specific interaction between the major viral capsid protein VP1 and its cell surface ganglioside receptor GM1. Here we show that late during infection, SV40 activates a signaling cascade in permissive CV-1 monkey cells involving Ras, Rac1, MKK4 and JNK to induce SV40-specific cytoplasmic vacuolization and subsequent cell lysis and virus release. Inhibition of individual components of this signaling pathway inhibits vacuolization, lysis and virus release, even though high-level intracellular virus replication occurs. The identification of this pathway for SV40-induced vacuolization and virus release provides new insight...Continue Reading

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Mentioned in this Paper

Pathologic Cytolysis
MAP2K4 protein, human
Study
Biochemical Pathway
AKT1
Signaling Cascade
Virus
Virus Diseases
Antibiotic CV-1
Ganglioside receptor

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