Expression of herpes simplex virus ICP0 inhibits the induction of interferon-stimulated genes by viral infection.
The herpes simplex virus type 1 (HSV-1) mutant d109 does not express any of the immediate-early (IE) proteins and persists in cells for a prolonged length of time. As has been shown by Nicholl et al. (J. Gen. Virol. 81:2215-2218, 2000) and Mossman et al. (J. Virol. 75:750-758, 2001) using other mutants defective for IE gene expression, infection with d109 induced the expression of a number of interferon-stimulated genes. Induction of these genes was significantly greater at multiplicities of infection (MOI) of 10 PFU/cell or greater, and the resulting antiviral effect was only seen at MOIs greater than 10 PFU/cell. Using mutants defective for sets of IE genes established that the lack of ICP0 expression was necessary for high levels of interferon-stimulated gene expression in HEL cells. The induction of interferon-stimulated genes by d109 could also be inhibited by infection with an E1-:E3-:E4- adenovirus expressing levels of ICP0 that are comparable to those expressed within the first hour of wild-type virus infection. Lastly, the addition of the proteasome inhibitor MG132 to cells infected with a mutant that expresses ICP0, d106, also resulted in the induction of interferon-stimulated genes. Thus, ICP0 may function through the proteasome very early in HSV infection to inhibit a cellular antiviral response induced by the virion.
Eidson
Kasey M
KM
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Hobbs
William E
WE
Manning
Brian J
BJ
Carlson
Paul
P
DeLuca
Neal A
NA
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007372:Interferons / Q000276:immunology / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D044767:Ubiquitin-Protein Ligases; D014709:Vero Cells; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D017874:Immediate-Early Proteins; D007372:Interferons; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1