Vaccinia virus blocks Stat1-dependent and Stat1-independent gene expression induced by type I and type II interferons

Brandon A. Mann, Julia He Huang, Ping Li, Hua Chen Chang, Roger B. Slee, Audrey O'Sullivan, Anita Mathur, Norman Yeh, Michael Klemsz, Randy Brutkiewicz, Janice Blum, Mark Kaplan

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Blocking the function of Stat (signal transducer and activator of transcription) proteins, which are critical for antiviral responses, has evolved as a common mechanism for pathogen immune evasion. The poxvirus-encoded phosphatase H1 is critical for viral replication, and may play an additional role in the evasion of host defense by dephosphorylating Stat1 and blocking interferon (IFN)-stimulated innate immune responses. Vaccinia virus (VACV) H1 can inhibit the phosphorylation of the transcription factor Stat1 after IFN-γ stimulation of epithelial cells, greatly attenuating IFN-induced biological functions. In this study, we demonstrate that VACV infection is capable of inhibiting the phosphorylation of Stat1 and Stat2 after stimulation of fibroblasts or bone marrow-derived macrophages with either type I or type II IFNs, but did not inhibit the activation of Stat3 or Stat5 in either cell type. By using recombinant proteins for in vitro assays, we observe that variola virus H1 is more active than VACV H1, although it has similar selectivity for Stat targets. Differential effects of VACV infection were observed on the induction of IFN-stimulated genes, with complete inhibition of some genes by VACV infection, while others were less affected. Despite the IFN-γ-induced expression of some genes in VACV-infected cells, IFN-γ was unable to rescue the VACV-mediated inhibition of MHC class II antigen presentation. Moreover, VACV infection can affect the IFN-induced expression of Stat1-dependent and Stat1-independent genes, suggesting that the virus may target additional IFN-activated pathways. Thus, VACV targets multiple signaling pathways in the evasion of antiviral immune responses.

Original languageEnglish
Pages (from-to)367-379
Number of pages13
JournalJournal of Interferon and Cytokine Research
Volume28
Issue number6
DOIs
StatePublished - Jun 2008

Fingerprint

Interferon Type I
Vaccinia virus
Interferon-gamma
Interferons
Gene Expression
Virus Diseases
Immune Evasion
Antiviral Agents
Variola virus
Phosphorylation
STAT Transcription Factors
Genes
Poxviridae
Histocompatibility Antigens Class II
Antigen Presentation
Transducers
Phosphoric Monoester Hydrolases
Recombinant Proteins
Innate Immunity
Transcription Factors

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology

Cite this

Vaccinia virus blocks Stat1-dependent and Stat1-independent gene expression induced by type I and type II interferons. / Mann, Brandon A.; Huang, Julia He; Li, Ping; Chang, Hua Chen; Slee, Roger B.; O'Sullivan, Audrey; Mathur, Anita; Yeh, Norman; Klemsz, Michael; Brutkiewicz, Randy; Blum, Janice; Kaplan, Mark.

In: Journal of Interferon and Cytokine Research, Vol. 28, No. 6, 06.2008, p. 367-379.

Research output: Contribution to journalArticle

Mann, Brandon A. ; Huang, Julia He ; Li, Ping ; Chang, Hua Chen ; Slee, Roger B. ; O'Sullivan, Audrey ; Mathur, Anita ; Yeh, Norman ; Klemsz, Michael ; Brutkiewicz, Randy ; Blum, Janice ; Kaplan, Mark. / Vaccinia virus blocks Stat1-dependent and Stat1-independent gene expression induced by type I and type II interferons. In: Journal of Interferon and Cytokine Research. 2008 ; Vol. 28, No. 6. pp. 367-379.
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AU - Slee, Roger B.

AU - O'Sullivan, Audrey

AU - Mathur, Anita

AU - Yeh, Norman

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