Low expression of RNA sensors impacts Zika virus infection in the lower female reproductive tract

Shahzada Khan, Irene Lew, Frank Wu, Linda Fritts, Krystal A. Fontaine, Sakshi Tomar, Martin Trapecar, Hesham M. Shehata, Melanie Ott, Christopher J. Miller, Shomyseh Sanjabi

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Abstract

Innate immune responses to Zika virus (ZIKV) are dampened in the lower female reproductive tract (LFRT) compared to other tissues, but the mechanism that underlies this vulnerability is poorly understood. Using tissues from uninfected and vaginally ZIKV-infected macaques and mice, we show that low basal expression of RNA-sensing pattern recognition receptors (PRRs), or their co-receptors, in the LFRT contributes to high viral replication in this tissue. In the LFRT, ZIKV sensing provides limited protection against viral replication, and the sensors are also minimally induced after vaginal infection. While IFNα/β receptor signaling offers minimal protection in the LFRT, it is required to prevent dissemination of ZIKV to other tissues, including the upper FRT. Our findings support a role for RNA-sensing PRRs in the dampened innate immunity against ZIKV in the LFRT compared to other tissues and underlie potential implications for systemic dissemination upon heterosexual transmission of ZIKV in women.

Original languageEnglish (US)
Article number4344
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Khan, S., Lew, I., Wu, F., Fritts, L., Fontaine, K. A., Tomar, S., Trapecar, M., Shehata, H. M., Ott, M., Miller, C. J., & Sanjabi, S. (2019). Low expression of RNA sensors impacts Zika virus infection in the lower female reproductive tract. Nature communications, 10(1), [4344]. https://doi.org/10.1038/s41467-019-12371-7