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 and Shomyseh Sanjabi ()
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Shahzada Khan: Gladstone Institutes
Irene Lew: Gladstone Institutes
Frank Wu: Gladstone Institutes
Linda Fritts: University of California, Davis
Krystal A. Fontaine: Gladstone Institutes
Sakshi Tomar: Gladstone Institutes
Martin Trapecar: Gladstone Institutes
Hesham M. Shehata: Gladstone Institutes
Melanie Ott: Gladstone Institutes
Christopher J. Miller: University of California, Davis
Shomyseh Sanjabi: Gladstone Institutes

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12371-7

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