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Author Notes:

Correspondence to: virgin@wustl.edu

These authors contributed equally: HSC and MMH

These authors contributed equally: RJX, MHK, RP, and SHS

TAR designed the project, performed experiments, and wrote the paper.

HWV assisted with project design and paper writing.

BSW and SHS defined promoters and performed promoter assays.

XZ created and characterized MHV68-cre virus, performed LD-PCR and western blots.

HSC and RR performed KSHV experiments.

MMH and MHK performed ChIP experiments.

SCH and EJP helped design helminth experiments and supplied reagents.

MDB did RT-PCR for gene 50 and host genes.

AJ did flow cytometry with IL-4 in RAW264.7 cells.

AK did western blots.

CYL did plaque assays.

GG and RX did initial bioinformatic analysis of gene expression by array, later replaced with RNASeq.

PJM provided arginase mice.

MNA analyzed sequencing data.

The authors would like to thank R. Schreiber and K. Sheehan for supplying anti-IFNγ and PIP; G.Randolph and E. Gautier for PPARγ f/f×LyzMcre mice and helpful discussion; J. Urban for help setting up the H. polygyrus system; D. Kreamalmeyer for animal care and breeding; members of the Virgin lab for manuscript review and discussion; the Genome Technology Access Center at Washington University for sequencing; and the Flow Cytometry Core at Washington University for assistance with sorting.

Subject:

Research Funding:

TAR was supported by Damon Runyon Postdoctoral Fellowship.

This work was supported by grant U54 AI057160 and RO1 CA96511 to HWV, and grant AI032573 to EJP.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • MURINE GAMMAHERPESVIRUS 68
  • SWITCH GENE 50
  • B-CELLS
  • MACROPHAGES
  • INTERFERON
  • VIRUS
  • TRANSACTIVATOR
  • PROLIFERATION
  • ESTABLISHMENT
  • INFLAMMATION

Helminth infection reactivates latent gamma-herpesvirus via cytokine competition at a viral promoter

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Journal Title:

Вестник Волгоградского государственног... / Science Journal of Volgograd State University. History. Area Studies. International Relations

Volume:

Volume 345, Number 6196

Publisher:

, Pages 573-577

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Mammals are coinfected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine γ-herpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-γ (IFNγ) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi's sarcoma-associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFNγ reactivated latent murine γ-herpesvirus infection in vivo, suggesting a "two-signal" model for viral reactivation. Thus, chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status.

Copyright information:

© 2014, American Association for the Advancement of Science

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