The preferential cytotoxicity of reovirus for certain transformed cell lines

Abstract

The susceptibility of a variety of cell lines of different mammalian origin to cytotoxic (CT) induction by either ultraviolet light-irradiated reovirus type 2 (UVR2) or viable reovirus type 2 plus the protein synthesis inhibitor, cycloheximide, was examined. The following groups of cells were found to be susceptible to CT-induction: certain tumor cells and spontaneously transformed cell lines of human origin and certain virally and spontaneously transformed cell lines of murine origin. The following groups of cells were found to be resistant: normal human diploid cell lines, primary and continuous cell cultures of subhuman primates, primary mouse cells, normal rat kidney cells and baby hamster kidney cells. Susceptibility to CT-induction could not be related to the adsorption of virus to cells, nor to the capacity of the cell to support virus replication.

CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway

“…[3][4][5] However, the reovirus shows dramatic cytolytic activity in certain types of transformed cells. 6,7 There is a strong body of evidence that Ras-transformed cells are preferentially susceptible to reovirus (type 3 Dearing strain) through inactivation of PKR (dsRNAactivated protein kinase) phosphorylation, 8,9 and activation of the oncogenic Ras-signaling pathway enhances reoviral oncolytic targeting in various types of human cancers, 10,11 although our recent study shows that other signaling pathways may also contribute to the susceptibility of a hepatic cancer cell to reoviral replication and oncolysis. 12 Reoviral efficacy has been examined in the treatment of gliomas and other cancers in immunocompetent hosts and has not been shown to produce significant toxicities.…”

Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial

“…It is a ubiquitous non-pathogenic agent, isolated from the respiratory and gastrointestinal tracts of humans 2,3 and it has not been associated with a specific clinical syndrome. 4 Reoviruses are selectively able to kill cells with an activated Ras signalling pathway in vitro and in vivo, [5][6][7][8] which can occur through Ras mutation or aberrant expression of upstream mitogenic signals such as overexpressed or mutated receptor tyrosine kinases. Therefore, reovirus represents a potentially useful treatment for a wide variety of solid and haematological tumours including pancreatic, colorectal, thyroid and lung cancers and acute myelogenous leukaemia.…”

Clinical development directions in oncolytic viral therapy

“…134 Although reovirus belongs to the Reoviridae family, which includes rotovirus, infection in humans is usually subclinical and limited to the upper respiratory and gastrointestinal tract. 135 Three viral serotypes have been isolated and all are commonly found in the environment as this virus possesses a highly stable unenveloped icosahedral capsid, thus it is estimated that nearly half of the population has been exposed and carries antibodies to the virus.…”