Promyelocytic leukemia protein mediates interferon-based anti-herpes simplex virus 1 effects Journal Article
| Authors: | Chee, A. V.; Lopez, P.; Pandolfi, P. P.; Roizman, B. |
| Article Title: | Promyelocytic leukemia protein mediates interferon-based anti-herpes simplex virus 1 effects |
| Abstract: | Herpes simplex virus (HSV) 1 disaggregates the nuclear domain 10 (ND10) nuclear structures and disperses its organizing promyelocytic leukemia protein (PML). An earlier report showed that ectopic overexpression of PML precludes the disaggregation of ND10 but has no effect on viral replication. PML has been reported to mediate the effects of interferon (IFN) and viral mutants lacking ICP0 (Δα0 mutants). To test the hypothesis that HSV disaggregates ND10 structures and disperses PML to preclude IFN-mediated antiviral effects, we tested the accumulation of viral proteins and virus yields from murine PML +/+ and PML -/- cells mock treated or exposed to IFN-α, IFN-γ, or both and infected with the wild-type or Δα0 mutant virus. We report the following results. (i) The levels of growth of wild-type and mutant viruses and of accumulation of viral proteins were not significantly different in untreated PML +/+ and PML -/- cells. (ii) Major effects of IFN-α and -γ were observed in PML +/+ cells infected with the Δα0 mutant virus, and more minor effects were observed in cells infected with the wild-type virus. The effects of the IFNs on either wild-type or the mutant virus in PML -/- cells were minimal. (iii) The mixture of IFN-α and -γ was more effective than either IFN alone, but again, the effect was more drastic in PML +/+ cells than in PML -/- cells. We concluded that the anti-HSV state induced by exogenous IFN is mediated by PML and that the virus targets the ND10 structures and disseminates PML in order to preclude the establishment of the antiviral state induced by IFNs. |
| Keywords: | controlled study; unclassified drug; human cell; mutation; interferon; drug efficacy; nonhuman; alpha interferon; protein function; animal cell; mouse; animals; mice; cell structure; gene overexpression; neoplasm proteins; cell line; protein; herpes simplex; drug effect; wild type; transcription factors; nuclear proteins; gene expression regulation; statistical significance; gamma interferon; tumor suppressor proteins; herpesvirus 1, human; virus replication; herpes simplex virus 1; antiviral activity; virus mutant; interferon-alpha; virus protein; viral proteins; antiviral agents; hypothesis; promyelocytic leukemia protein; interferon type ii; cell nucleus structures; human; priority journal; article; infected cell protein number 0; nuclear domain 10 |
| Journal Title: | Journal of Virology |
| Volume: | 77 |
| Issue: | 12 |
| ISSN: | 0022-538X |
| Publisher: | American Society for Microbiology |
| Date Published: | 2003-06-01 |
| Start Page: | 7101 |
| End Page: | 7105 |
| Language: | English |
| DOI: | 10.1128/jvi.77.12.7101-7105.2003 |
| PUBMED: | 12768029 |
| PROVIDER: | scopus |
| PMCID: | PMC156157 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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