Activated Ras signaling significantly enhances reovirus replication and spread

Shmulevitz, Maya; Marcato, Paola; Lee, P W K

doi:10.1038/cgt.2009.46

Cited by 28 publications

(23 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in RAS-negative fibroblasts, all reovirus subtypes did not show oncolytic activity. These observations are in accordance with previous studies (5,10,11,(14)(15)(16).…”

Section: Discussionsupporting

confidence: 94%

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

Alloussi

Alkassar²,

Urbschat³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. Reoviridae are non-human pathogenic viruses. The family of reoviridae consists of 4 different subtypes. Many studies have proven that the Dearing subtype 3 has oncolytic potential. This potential is related to the RAS protein expression in tumour cells. The aim of this study, was to investigate whether all reovirus subtypes have oncolytic potential and whether there are differences in their efficacy, in particular for high-grade glioma. To evaluate the oncolytic potential, we performed an in vitro head-to-head study for all reovirus subtypes in 5 primary cell cultures of high-grade gliomas. The oncolytic activity was determined using end-point titration with observation of the cytopathogenic effect. For measurement of RAS activity, we performed an immunofluorescent detection stain on all cell cultures. For quantification of the virus, an RT-PCR measurement for all subtypes was performed. All reovirus subtypes showed oncolytic activity in the observed glioma biopsies. These observations correlated with RAS overexpression in the observed cells. All glioma biopsies overexpressed the RAS protein. The quantitative oncolytic potential differed in relation to the single observed cell culture and in relation to the chosen reovirus subtype. To our knowledge, this is the first study showing oncolytic activity for all reovirus subtypes. We show the relationship and correlation between RAS protein overexpression and vulnerability of cells to reovirus. Efficacy of the different subtypes is interindividually different and cannot be forecast.

show abstract

“…However, in RAS-negative fibroblasts, all reovirus subtypes did not show oncolytic activity. These observations are in accordance with previous studies (5,10,11,(14)(15)(16).…”

Section: Discussionsupporting

confidence: 94%

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

Alloussi

Alkassar²,

Urbschat³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…These antireovirus immune responses can inhibit replication and spread of reovirus into tumor cells, and thus impair efficacy of oncolysis. On the other hand, when reovirus-specific T cells mount an attack on reovirus-infected cells, they essentially target tumor cells as reovirus preferentially infects cancerous cells (48). This inadvertent antireovirus Tcell-mediated destruction of tumor cells can additionally contribute to the oncolytic activities of reovirus anticancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

Gujar

Marcato

Pan

et al. 2010

Molecular Cancer Therapeutics

105

View full text Add to dashboard Cite

Tumor-associated immunosuppressive strategies, such as lack of tumor antigen recognition and failure of lymphocyte activation and homing, resist the development of tumor-specific immunity and hamper the immune response-mediated elimination of cancerous cells. In this report, we show that reovirus virotherapy overrides such a tumor immune evasion and establishes clinically meaningful antitumor immunity capable of protecting against subsequent tumor challenge. Reovirus-mediated destruction of tumor cells facilitates the recognition of tumor antigens by promoting the display of otherwise inaccessible tumorspecific immunogenic peptides on the surface of dendritic cells (DC). Furthermore, on exposure to reovirus, DCs produce IL-1α, IL-1β, IL-6, IL-12p40/70, IL-17, CD30L, eotaxin, GM-CSF, KC, MCP-1, MCP-5, M-CSF, MIG, MIP-1α, RANTES, TNF-α, VCAM-1, VSGF, CXCL-16, AXL, and MCP-2; undergo maturation; and migrate into the tumor microenvironment along with CD8 T cells. These reovirus-activated DCs also acquire the capacity to prime tumor antigen-specific transgenic T cells in vitro and intrinsic antitumor T-cell response in vivo. Further, reovirus virotherapy augments the efficacy of DC-or T cell-based anticancer immunotherapies and synergistically enhances the survival in tumor-bearing mice. Most importantly, antitumor cellular immune responses initiated during reovirus oncotherapy protect the host against subsequent tumor challenge in a reovirus-independent but antigen-dependent manner. These reovirus oncotherapy-initiated antitumor immune responses represent an anticancer therapeutic entity that can maintain a long-term cancer-free health even after discontinuation of therapy.

show abstract

“…Positively regulates RNA synthesis, vRNP export and release (budding) of IAV (Kumar et al, 2011a) PDGFR Facilitates KSHV tumor progression (Cao et al, 2015;Sturzl et al, 1992) GPCRs GPCRs Promotes membrane fusion and cell to cell spread in hHSV6 (mediated via viral U51 protein) (Zhen et al, 2005) Positively regulates replication and reactivation of gamma herpesvirus latency (mediated via viral CXCR2 protein) (Lee et al, 2003) Positively regulates flavivirus entry and RNA synthesis (Le Sommer et al, 2012) Ras/Akt N-Ras Promotes HCV replication by facilitating cell survival and establishment of persistent viral infection (Mannova and Beretta, 2005) Akt Promotes clathrin-independent endocytosis and internalization of IAV (Fujioka et al, 2011) Positively regulates PCV2 replication by inhibiting premature apoptosis (Wei et al, 2012) By expressing anti-apoptotic genes, positively regulates cowpox virus and vaccinia virus replication (Soares et al, 2009) Inhibits endocytic uptake of the influenza viruses (Denisova et al, 2014) mTORC2 Positively regulates adenovirus replication (mediated via viral proteins that mimic nutrient/growth signals regulating mTOR pathway) (O'Shea et al, 2005) Ras/Raf/MEK/ERK Ras Positively regulates reovirus replication and spread (Shmulevitz et al, 2010)…”

Section: Ngfrmentioning

confidence: 99%

Role of MAPK/MNK1 signaling in virus replication

et al. 2018

View full text Add to dashboard Cite

Viruses are obligate intracellular parasites; they heavily depend on the host cell machinery to effectively replicate and produce new progeny virus particles. Following viral infection, diverse cell signaling pathways are initiated by the cells, with the major goal of establishing an antiviral state. However, viruses have been shown to exploit cellular signaling pathways for their own effective replication. Genome-wide siRNA screens have also identified numerous host factors that either support (proviral) or inhibit (antiviral) virus replication. Some of the host factors might be dispensable for the host but may be critical for virus replication; therefore such cellular factors may serve as targets for development of antiviral therapeutics. Mitogen activated protein kinase (MAPK) is a major cell signaling pathway that is known to be activated by diverse group of viruses. MAPK interacting kinase 1 (MNK1) has been shown to regulate both cap-dependent and internal ribosomal entry sites (IRES)-mediated mRNA translation. In this review we have discuss the role of MAPK in virus replication, particularly the role of MNK1 in replication and translation of viral genome.

show abstract

Activated Ras signaling significantly enhances reovirus replication and spread

Cited by 28 publications

References 9 publications

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma

Reovirus Virotherapy Overrides Tumor Antigen Presentation Evasion and Promotes Protective Antitumor Immunity

Role of MAPK/MNK1 signaling in virus replication

Contact Info

Product

Resources

About