Aagaard

Barrows

Bayer

Bin Cao

Cadwell

Cao-Lormeau

Cemma

Chibueze

Chiramel

Delorme-Axford

Delvecchio

El Costa

Elfiky

Eyer

Farias

Hamel

Indira U. Mysorekar

Jurado

Kaplan

Khan

Klionsky

Lamont

Lennemann

Levine

Liang

Lindsay A. Parnell

Martín-Acebes

Mateo

Michael S. Diamond

Miner

Mysorekar

Pirooz

Quicke

Rosenfeldt

Rossant

Sacramento

Savarino

Sharma

Shoji-Kawata

Signorelli

Tabata

Tricou

Vandergaast

Vermillion

Wenzel

Yockey

Zmurko

English

Cao, Bin

Parnell, Lindsay A

Diamond, Michael S

Mysorekar, Indira U

Digital Commons@Becker

Inhibition of autophagy limits vertical transmission of Zika virus in pregnant mice

Zika virus (ZIKV) infection during pregnancy leads to devastating fetal outcomes, including intrauterine growth restriction and microcephaly. Greater understanding of mechanisms underlying ZIKV maternal-fetal transmission is needed to develop new therapeutic interventions. Here, we define an important role for the autophagy pathway in ZIKV vertical transmission. ZIKV infection induced autophagic activity in human trophoblasts and pharmacological inhibition limited ZIKV infectivity. Furthermore, deficiency in an essential autophagy gene, Atg16l1, in mice limited ZIKV vertical transmission and placental and fetal damage and overall improved placental and fetal outcomes. This protection was due to a placental trophoblast cell-autonomous effect of autophagic activity, not to alterations in systemic maternal ZIKV infection. Finally, an autophagy inhibitor, hydroxychloroquine, approved for use in pregnant women, attenuated placental and fetal ZIKV infection and ameliorated adverse placental and fetal outcomes. Our study reveals new insights into the mechanism of ZIKV vertical transmission and suggests that an autophagy-based therapeutic warrants possible evaluation in humans to diminish the risks of ZIKV maternal-fetal transmission.</jats:p

Crossref

The Journal of Experimental Medicine

https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=7132&amp;context=open_access_pubs

Inhibition of autophagy limits vertical transmission of Zika virus in pregnant mice

Abstract

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