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

T. A. Reese, B. S. Wakeman, H. S. Choi, M. M. Hufford, S. C. Huang, X. Zhang, M. D. Buck, A. Jezewski, A. Kambal, C. Y. Liu, G. Goel, P. J. Murray, R. J. Xavier, M. H. Kaplan, R. Renne, S. H. Speck, M. N. Artyomov, E. J. Pearce, H. W. Virgin

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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.

Original languageEnglish (US)
Pages (from-to)573-577
Number of pages5
JournalScience
Volume345
Issue number6196
DOIs
StatePublished - Aug 1 2014

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Helminths
Herpesviridae
Herpesviridae Infections
Interleukin-4
Cytokines
Infection
Interferons
Human Herpesvirus 8
Trans-Activators
Antiviral Agents
Mammals
Cultured Cells
Transcription Factors

ASJC Scopus subject areas

  • General

Cite this

Reese, T. A., Wakeman, B. S., Choi, H. S., Hufford, M. M., Huang, S. C., Zhang, X., ... Virgin, H. W. (2014). Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter. Science, 345(6196), 573-577. https://doi.org/10.1126/science.1254517

Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter. / Reese, T. A.; Wakeman, B. S.; Choi, H. S.; Hufford, M. M.; Huang, S. C.; Zhang, X.; Buck, M. D.; Jezewski, A.; Kambal, A.; Liu, C. Y.; Goel, G.; Murray, P. J.; Xavier, R. J.; Kaplan, M. H.; Renne, R.; Speck, S. H.; Artyomov, M. N.; Pearce, E. J.; Virgin, H. W.

In: Science, Vol. 345, No. 6196, 01.08.2014, p. 573-577.

Research output: Contribution to journalArticle

Reese, TA, Wakeman, BS, Choi, HS, Hufford, MM, Huang, SC, Zhang, X, Buck, MD, Jezewski, A, Kambal, A, Liu, CY, Goel, G, Murray, PJ, Xavier, RJ, Kaplan, MH, Renne, R, Speck, SH, Artyomov, MN, Pearce, EJ & Virgin, HW 2014, 'Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter', Science, vol. 345, no. 6196, pp. 573-577. https://doi.org/10.1126/science.1254517
Reese, T. A. ; Wakeman, B. S. ; Choi, H. S. ; Hufford, M. M. ; Huang, S. C. ; Zhang, X. ; Buck, M. D. ; Jezewski, A. ; Kambal, A. ; Liu, C. Y. ; Goel, G. ; Murray, P. J. ; Xavier, R. J. ; Kaplan, M. H. ; Renne, R. ; Speck, S. H. ; Artyomov, M. N. ; Pearce, E. J. ; Virgin, H. W. / Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter. In: Science. 2014 ; Vol. 345, No. 6196. pp. 573-577.
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AU - Buck, M. D.

AU - Jezewski, A.

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AU - Goel, G.

AU - Murray, P. J.

AU - Xavier, R. J.

AU - Kaplan, M. H.

AU - Renne, R.

AU - Speck, S. H.

AU - Artyomov, M. N.

AU - Pearce, E. J.

AU - Virgin, H. W.

PY - 2014/8/1

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