[Investigation of host cell protein synthesis shut-off inhibition by a Herpes simplex virus type-1 gene, ICP34.5, in a neuronal cell line, SK-N-SH]

ABSTRACT

Background and aim: the cellular response to virus infection is a complex process and includes induction of interferons [IFNs]. IFNs are key components of the host innate immunity to virus infection and act through several pathways to block virus growth and virulence. Cells infected with a variety of viruses synthesize double stranded RNA, which induces an IFN response. Protein kinase R [PKR] is induced by IFNs and is a major mediator of the cellular response to virus infection. PKR becomes activated and phosphorylates initiation factor-2alpha [eIF-2alpha]. This leads to the loss of functional eIF-2alpha, which results in inhibition of protein synthesis. In herpes simplex virus type-1 [HSV-1] infected cells, activation of the PKR pathway results in premature shut-off of host protein synthesis. However, HSV-1 encodes a gene, ICP34.5, which blocks the shut-off of the host protein synthesis. This gene is the virulence factor of this virus in the central nervous system of the mice. This gene is not essential for replication of this virus in some cell lines. However, its role in neuronal cell lines such as SK-N-SH cells following infection with recombinant mutant expressing ICP34.5 specifically, has not been investigated. The aim of this research was to investigate this role