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IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.

Publication ,  Journal Article
Kwock, JT; Handfield, C; Suwanpradid, J; Hoang, P; McFadden, MJ; Labagnara, KF; Floyd, L; Shannon, J; Uppala, R; Sarkar, MK; Gudjonsson, JE ...
Published in: Sci Adv
April 2020

In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27-mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus.

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Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

April 2020

Volume

6

Issue

14

Start / End Page

eaay3245

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Skin
  • Signal Transduction
  • STAT1 Transcription Factor
  • Keratinocytes
  • Interleukins
  • Immunity, Innate
  • Humans
  • Host-Pathogen Interactions
 

Citation

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Kwock, J. T., Handfield, C., Suwanpradid, J., Hoang, P., McFadden, M. J., Labagnara, K. F., … MacLeod, A. S. (2020). IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection. Sci Adv, 6(14), eaay3245. https://doi.org/10.1126/sciadv.aay3245
Kwock, Jeffery T., Chelsea Handfield, Jutamas Suwanpradid, Peter Hoang, Michael J. McFadden, Kevin F. Labagnara, Lauren Floyd, et al. “IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.Sci Adv 6, no. 14 (April 2020): eaay3245. https://doi.org/10.1126/sciadv.aay3245.
Kwock JT, Handfield C, Suwanpradid J, Hoang P, McFadden MJ, Labagnara KF, et al. IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection. Sci Adv. 2020 Apr;6(14):eaay3245.
Kwock, Jeffery T., et al. “IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.Sci Adv, vol. 6, no. 14, Apr. 2020, p. eaay3245. Pubmed, doi:10.1126/sciadv.aay3245.
Kwock JT, Handfield C, Suwanpradid J, Hoang P, McFadden MJ, Labagnara KF, Floyd L, Shannon J, Uppala R, Sarkar MK, Gudjonsson JE, Corcoran DL, Lazear HM, Sempowski G, Horner SM, MacLeod AS. IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection. Sci Adv. 2020 Apr;6(14):eaay3245.

Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

April 2020

Volume

6

Issue

14

Start / End Page

eaay3245

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Skin
  • Signal Transduction
  • STAT1 Transcription Factor
  • Keratinocytes
  • Interleukins
  • Immunity, Innate
  • Humans
  • Host-Pathogen Interactions