Gestational Stage and IFN-λ Signaling Regulate ZIKV Infection In Utero.

Jagger, Brett W

Miner, Jonathan J

Cao, Bin

Arora, Nitin

Smith, Amber M

Kovacs, Attila

Mysorekar, Indira U

Coyne, Carolyn B

Diamond, Michael S

2021-04-16T20:00:12Z

2021-04-16T20:00:12Z

2017-09

2021-04-16T20:00:06Z

Although Zika virus (ZIKV)-induced congenital disease occurs more frequently during early stages of pregnancy, its basis remains undefined. Using established type I interferon (IFN)-deficient mouse models of ZIKV transmission in utero, we found that the placenta and fetus were more susceptible to ZIKV infection at earlier gestational stages. Whereas ZIKV infection at embryonic day 6 (E6) resulted in placental insufficiency and fetal demise, infections at midstage (E9) resulted in reduced cranial dimensions, and infection later in pregnancy (E12) caused no apparent fetal disease. In addition, we found that fetuses lacking type III IFN-λ signaling had increased ZIKV replication in the placenta and fetus when infected at E12, and reciprocally, treatment of pregnant mice with IFN-λ2 reduced ZIKV infection. IFN-λ treatment analogously diminished ZIKV infection in human midgestation fetal- and maternal-derived tissue explants. Our data establish a model of gestational stage dependence of ZIKV pathogenesis and IFN-λ-mediated immunity at the maternal-fetal interface.

S1931-3128(17)30345-1

1931-3128

1934-6069

https://hdl.handle.net/10161/22588

eng

Elsevier BV

Cell host & microbe

10.1016/j.chom.2017.08.012

Animals

Mice, Inbred C57BL

Humans

Mice

Pregnancy Complications, Infectious

Fetal Diseases

Disease Models, Animal

Receptors, Interferon

Cytokines

Gestational Age

Pregnancy

Female

Male

Zika Virus

Zika Virus Infection

Gestational Stage and IFN-λ Signaling Regulate ZIKV Infection In Utero.

Journal article

Coyne, Carolyn B|0000-0002-1884-6309

366

376.e3

3

School of Medicine

Molecular Genetics and Microbiology

Duke

Basic Science Departments

Published

22