Herpes simplex virus ICP0 and ICP34.5 counteract distinct interferon-induced barriers to virus replication - PubMed (original) (raw)

Herpes simplex virus ICP0 and ICP34.5 counteract distinct interferon-induced barriers to virus replication

Karen L Mossman et al. J Virol. 2002 Feb.

Abstract

Interferon inhibits virus replication through multiple mechanisms. Here we show that herpes simplex virus proteins ICP0 and ICP34.5 overcome interferon-induced barriers to viral transcription and translation, respectively. These cytokine-induced antiviral mechanisms are differentially expressed in established cell lines: U2OS cells do not mount the IFN-induced mechanism targeted by ICP0, and Vero cells may be defective for the mechanism targeted by ICP34.5.

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Figures

FIG. 1.

FIG. 1.

ICP0 functions to overcome an IFN-induced block to viral transcription. Transcription levels were measured by nuclear run on analysis in Vero and U2OS cells either mock treated or pretreated with IFN-α prior to infection with wild type-HSV-1 (KOS and termAR) or mutant _n_212 (ICP0−) or termA (ICP34.5−). Nuclei were harvested 6 h postinfection, and transcription was allowed to proceed in the presence of radiolabeled UTP. RNA products were purified and hybridized to membranes bearing single-stranded DNA probes designed to detect sense transcription of the indicated viral genes.

FIG. 2.

FIG. 2.

ICP34.5 functions to overcome an IFN-induced block to translation. Vero and U2OS cells either mock treated or pretreated with IFN-α were infected with 5 PFU/cell termA or termAR, incubated for the indicated times (in hours), and then labeled with [35S]cysteine-methionine for 1 h. Lysates were subjected to SDS-PAGE analysis and visualized by autoradiography.

FIG. 3.

FIG. 3.

Effect of IFN-α pretreatment on accumulation of viral IE mRNA. Vero and U2OS cells were mock treated or pretreated with IFN-α prior to infection with 5 PFU of either _n_212 (ICP0−) or termA (ICP34.5−) per cell. Total RNA was harvested 6 h postinfection, and ICP27 transcript levels were analyzed by Northern blot analysis. Arrow indicates ICP27 mRNA.

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