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 language | English (US) |
|---|---|
| Article number | 4344 |
| Journal | Nature communications |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - 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
Low expression of RNA sensors impacts Zika virus infection in the lower female reproductive tract. / Khan, Shahzada; Lew, Irene; Wu, Frank; Fritts, Linda; Fontaine, Krystal A.; Tomar, Sakshi; Trapecar, Martin; Shehata, Hesham M.; Ott, Melanie; Miller, Christopher J.; Sanjabi, Shomyseh.
In: Nature communications, Vol. 10, No. 1, 4344, 01.12.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Low expression of RNA sensors impacts Zika virus infection in the lower female reproductive tract
AU - Khan, Shahzada
AU - Lew, Irene
AU - Wu, Frank
AU - Fritts, Linda
AU - Fontaine, Krystal A.
AU - Tomar, Sakshi
AU - Trapecar, Martin
AU - Shehata, Hesham M.
AU - Ott, Melanie
AU - Miller, Christopher J.
AU - Sanjabi, Shomyseh
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-12371-7
DO - 10.1038/s41467-019-12371-7
M3 - Article
C2 - 31554802
AN - SCOPUS:85072667913
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4344
ER -