STAT-1 and IRF-3 dependent pathways are not essential for repression of ICP0-null mutant herpes simplex virus type 1 in human fibroblasts

Everett, R.D., Young, D.F., Randall, R.E. and Orr, A. (2008) STAT-1 and IRF-3 dependent pathways are not essential for repression of ICP0-null mutant herpes simplex virus type 1 in human fibroblasts. Journal of Virology, 82(17), pp. 8871-8881. (doi: 10.1128/JVI.00613-08)

Abstract

Efficient herpes simplex virus type 1 (HSV-1) infection of human fibroblasts (HFs) is highly dependent on the viral immediate-early regulatory protein ICP0, unless the infection is conducted at high multiplicity. ICP0-null mutant HSV-1 exhibits a plaque forming defect of up to three orders of magnitude in HFs, whereas in many other cell types this defect varies between 10- and 30-fold. The reasons for the high ICP0 requirement for HSV-1 infection in HFs have not been established definitively. Previous studies using other cell types have suggested that ICP0-null mutant HSV-1 is hypersensitive to interferon and that this sensitivity is dependent on the cellular PML protein. To investigate the roles of two important aspects of interferon signalling in the phenotype of ICP0-null mutant HSV-1, we isolated HFs depleted of STAT-1 or IRF-3. Surprisingly, plaque formation by the mutant virus was not improved in either cell type. We found that the sensitivity to interferon pre-treatment of both ICP0-null mutant and wt HSV-1 was highly dependent on multiplicity of infection. At low multiplicity in virus yield experiments, both viruses were extremely susceptible to interferon pre-treatment of HFs, but the sensitivity of the wild type but not the mutant could be overcome at higher multiplicities. We found that both wt and ICP0 null-mutant HSV-1 remained sensitive to interferon in PML-depleted HFs, albeit to an apparently lesser extent than in control cells. The data imply that the substantial reduction in ICP0-null HSV-1 infectivity at low multiplicity in HFs does not occur through the activities of STAT-1 and IRF-3 dependent pathways and cannot be explained solely by enhanced sensitivity to interferon. We suggest that antiviral activities induced by interferon may be separable from and additive to those resulting from PML-related intrinsic resistance mechanisms

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Everett, Professor Roger
• Authors: Everett, R.D., Young, D.F., Randall, R.E., and Orr, A.
• Subjects: Q Science > QR Microbiology > QR355 Virology
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Virology
• Journal Abbr.: J. Virol.
• ISSN: 0022-538X
• ISSN (Online): 1098-5514