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.
Figures
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.
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.
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.
References
- Berlanga, J. J., J. Santoyo, and C. De Haro. 1999. Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase. Eur. J. Biochem. 265:754-762. - PubMed
- Cassady, K. A., M. Gross, and B. Roizman. 1998. The herpes simplex virus US11 protein effectively compensates for the gamma1(34.5) gene if present before activation of protein kinase R by precluding its phosphorylation and that of the alpha subunit of eukaryotic translation initiation factor 2. J. Virol. 72:8620-8626. - PMC - PubMed
- Chelbi-Alix, M. K., and H. deThe. 1999. Herpes virus induced proteosome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. Oncogene 18:935-941. - PubMed
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