A laboratory-attenuated vesicular stomatitis virus induces apoptosis and alters the cellular microRNA expression profile in BHK cells

Abstract

In the present study, we characterized the pathways by which a laboratory-attenuated vesicular stomatitis virus (La-VSV) induces apoptosis in BHK cells. It was found that La-VSV induced a loss of mitochondrial membrane potential (ΔΨm) and activated caspase-9 and -3, but not caspase-8, indicating that the induction of apoptosis by La-VSV may involve an intrinsic apoptotic pathway. Although aberrant expression of microRNAs (miRNAs) has been linked to viral infection, little is known about changes in the cellular miRNA expression profile following VSV infection. Here, we attempted to identify miRNA expression profiles in VSV-infected BHK cells using miRNA microarray. Data analysis revealed that 28 miRNAs consistently responded to VSV-infection, 12 of which were down-regulated and 16 of which were up-regulated. miR-146a of these miRNAs has been found to be up-regulated in LPS-stimulated monocytes and VSV-infected macrophages, suggesting that VSV-induced miR-146a expression occurs not only in immune cells but also in other host cells. We further found that miR-706 inhibited VSV-induced apoptosis by decreasing caspase-3 and -9 activation, suggesting that induction of miR-706 expression may be a novel strategy for survival of VSV, allowing it to escape the apoptosis response of the host. In summary, our results indicate that miRNAs might play important roles in VSV infection and that their aberrant expression could be involved in VSV pathogenesis.