Characterizing the CNS protection induced by systemic administration of the oncolytic mutant virus DeltaM51-VSV.

摘要

Direct brain infection with VSV in mice, including the attenuated DeltaM51 strain, results in widespread viral replication, leading to irreversible and often fatal damage. When DeltaM51-VSV is administered i.v., a trace amount of the virus is found within the brain, but is eventually cleared leaving the animal physically undamaged. In response to a peripheral infection, it seems that the host is able to mount an antiviral state in the CNS. Here, I show that by "priming" the host with mutant VSV prior to direct injection of VSV into the CNS, the host is able to send "warnings" in the form of cellular messengers and/or chemical signals preparing the brain to protect itself by any means possible against VSV. I used in vivo imaging techniques coupled with direct labelling of brain tissue sections to assess the effects of priming and CNS protection. My experiments indicate that priming mice with the interferon inducing mutant VSV, DeltaM51-VSV, is in fact CNS protective. Priming limits VSV spread in the brain not by preventing infection of neurons, but by rapid induction of apoptosis in either infected cells or cells neighbouring areas of active infection. Further investigation into the factor(s) or mechanism(s) mediating viral clearance and CNS protection indicates that the innate immune system is able to control and clear DeltaM51-VSV from the CNS before an adaptive response is required.