TY - JOUR
T1 - Interferon lambda protects the female reproductive tract against Zika virus infection
AU - Caine, Elizabeth A.
AU - Scheaffer, Suzanne M.
AU - Arora, Nitin
AU - Zaitsev, Konstantin
AU - Artyomov, Maxim N.
AU - Coyne, Carolyn B.
AU - Moley, Kelle H.
AU - Diamond, Michael S.
N1 - Funding Information:
This work was supported by grants from the NIH (R01 AI073755, R01 AI127828, and R01 HD091218 to M.S.D; T32AI055397 to E.C.; R01 AI081759 and HD075665 to C.B.C.; and R01 HD083895 to K.H.M.). In addition, work was supported by a Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease Award (C.B.C) and the Children’s Hospital of Pittsburgh of the UPMC Health System (C.B.C. and N.A.) K.Z. was supported by the Government of the Russian Federation (Grant 08-08). We thank Haina Shin for experimental advice and Sean Doyle (Zymogenetics, a Bristol-Myers Squibb company) for providing the Ifnlr1−/− mice and pegylated IFN-λ2.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Although Zika virus (ZIKV) can be transmitted sexually and cause congenital birth defects, immune control mechanisms in the female reproductive tract (FRT) are not well characterized. Here we show that treatment of primary human vaginal and cervical epithelial cells with interferon (IFN)-α/β or IFN-λ induces host defense transcriptional signatures and inhibits ZIKV infection. We also assess the effects of IFNs on intravaginal infection of the FRT using ovariectomized mice treated with reproductive hormones. We find that mice receiving estradiol are protected against intravaginal ZIKV infection, independently of IFN-α/β or IFN-λ signaling. In contrast, mice lacking IFN-λ signaling sustain greater FRT infection when progesterone is administered. Exogenous IFN-λ treatment confers an antiviral effect when mice receive both estradiol and progesterone, but not progesterone alone. Our results identify a hormonal stage-dependent role for IFN-λ in controlling ZIKV infection in the FRT and suggest a path for minimizing sexual transmission of ZIKV in women.
AB - Although Zika virus (ZIKV) can be transmitted sexually and cause congenital birth defects, immune control mechanisms in the female reproductive tract (FRT) are not well characterized. Here we show that treatment of primary human vaginal and cervical epithelial cells with interferon (IFN)-α/β or IFN-λ induces host defense transcriptional signatures and inhibits ZIKV infection. We also assess the effects of IFNs on intravaginal infection of the FRT using ovariectomized mice treated with reproductive hormones. We find that mice receiving estradiol are protected against intravaginal ZIKV infection, independently of IFN-α/β or IFN-λ signaling. In contrast, mice lacking IFN-λ signaling sustain greater FRT infection when progesterone is administered. Exogenous IFN-λ treatment confers an antiviral effect when mice receive both estradiol and progesterone, but not progesterone alone. Our results identify a hormonal stage-dependent role for IFN-λ in controlling ZIKV infection in the FRT and suggest a path for minimizing sexual transmission of ZIKV in women.
UR - http://www.scopus.com/inward/record.url?scp=85060132884&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-07993-2
DO - 10.1038/s41467-018-07993-2
M3 - Article
C2 - 30655513
AN - SCOPUS:85060132884
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 280
ER -