Herpes simplex virus ICP0 mutants are hypersensitive to interferon - PubMed (original) (raw)

Herpes simplex virus ICP0 mutants are hypersensitive to interferon

K L Mossman et al. J Virol. 2000 Feb.

Abstract

Interferon (IFN) is an important immune system molecule capable of inducing an antiviral state within cells. Herpes simplex virus type 1 (HSV-1) replication is somewhat reduced in tissue culture in the presence of IFN, presumably due to decreased viral transcription. Here, we show mutations that inactivate immediate-early (IE) gene product ICP0 render HSV-1 exquisitely sensitive to IFN inhibition, resulting in greatly decreased levels of viral mRNA transcripts and the resulting polypeptides and a severe reduction in plaque formation ability. Mutations in other HSV-1 genes, including the genes coding for virion transactivator VP16 and the virion host shutoff protein vhs, IE gene ICP22, and the protein kinase UL13 gene, do not increase the IFN sensitivity of HSV-1. Interestingly, ICP0 mutants demonstrate the same level of sensitivity to IFN as wild-type virus on U2OS cells, an osteosarcoma cell line that is known to complement mutations in ICP0 and VP16. Thus, in some cell types, functional ICP0 is required for HSV-1 to efficiently bypass the inhibitory effects of IFN in order to ensure its replication. The significance of this link between ICP0 and IFN resistance is discussed.

PubMed Disclaimer

Figures

FIG. 1

FIG. 1

Effect of IFN pretreatment on accumulation of viral mRNAs. Vero cells were mock treated (−) or pretreated (+) with 1,000 U of IFN-α per ml for 16 h prior to infection with 5 PFU of the indicated virus per cell. Total RNA was harvested either 4, 8, or 24 h postinfection by using Trizol (Gibco BRL). Aliquots (5 μg) were then analyzed for ICP4, ICP27, or ICP8 transcript levels by Northern blot analysis with 32P random-primer-labeled probe by using ExpressHyb (Clontech).

FIG. 2

FIG. 2

Effect of IFN pretreatment on accumulation of ICP4, ICP27, and ICP8. Vero cells were mock treated (−) or pretreated (+) with 1,000 U of IFN-α per ml for 16 h prior to infection with 5 PFU of the indicated virus per cell. Infected cells were harvested directly into sodium dodecyl sulfate-polyacrylamide gel electrophoresis sample buffer at 4, 8, and 24 h postinfection. Lysates were run on 9% polyacrylamide gels, transferred to nitrocellulose membranes, and blotted for ICP4, ICP27, or ICP8 protein by using a 1:2,000 dilution of GICR 1114, 1113, or 1115, respectively (Goodwin Institute for Cancer Research).

References

    1. Ace C I, McKee T A, Ryan J M, Cameron J M, Preston C M. Construction and characterization of a herpes simplex virus type 1 mutant unable to transinduce immediate-early gene expression. J Virol. 1989;63:2260–2269. - PMC - PubMed
    1. Altinkilic B, Brandner G. Interferon inhibits herpes simplex virus-specific translation: a reinvestigation. J Gen Virol. 1988;69:3107–3112. - PubMed
    1. Barry M, McFadden G. Virokines and viroceptors. In: Remick D G, Friedland J S, editors. Cytokines in health and disease. New York, N.Y: Marcel Dekker, Inc.; 1997. pp. 251–261.
    1. Burkham J, Coen D, Weller S K. ND10 protein PML is recruited to herpes simplex virus type 1 prereplicative sites and replication compartments in the presence of viral DNA polymerase. J Virol. 1998;72:10100–10107. - PMC - PubMed
    1. Cai W, Schaffer P A. Herpes simplex virus type 1 ICP0 plays a critical role in the de novo synthesis of infectious virus following transfection of viral DNA. J Virol. 1989;63:4579–4589. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources