Actin and its regulators are critical for neuronal function. Infection with herpes simplex virus 1 (HSV-1) remodels neuronal cell actin dynamics, which may relate virus-induced pathological processes in the nervous system. We previously demonstrated that cofilin is an actin regulator that participates in HSV-1-induced actin dynamics in neuronal cells, but how HSV-1 regulates cofilin has remained unclear. In the present study, we demonstrated the HSV-1-induced the inactivation of cofilin and the accumulation of phosphorylated cofilin in the nucleus, which together benefited viral replication. This consistent cofilin inactivation was achieved by the downregulation of slingshot 1 (SSH1). Notably, virus-induced SSH1 downregulation depended on the ubiquitin-proteasome system. Cofilin inactivation is therefore critical for HSV-1 replication during neuronal infection and is maintained by SSH1 downregulation. Moreover, these results provide new insight into the HSV-1-induced neurological pathogenesis and suggest potential new strategies to inhibit HSV-1 replication.
Keywords: Cofilin; F-actin; HSV-1; LIM kinase-1; LIMK1; SSH1; Ubiquitin-proteasome; actin filaments; herpes simplex virus 1; p-cofilin; phosphorylated cofilin; slingshot-1.
© 2013 Published by Elsevier Inc.