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Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection
Laura J. Yockey
, Luis Varela
, Tasfia Rakib
, William Khoury-Hanold
, Susan L. Fink
, Bernardo Stutz
, Klara Szigeti-Buck
, Anthony Van den Pol
, Brett D. Lindenbach
, Tamas L. Horvath
, Akiko Iwasaki7,
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7Lead Contact
DOI: http://dx.doi.org/10.1016/j.cell.2016.08.004 |
...
Highlights
Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy.
http://www.cell.com/cell/fulltext/S0092-8674(16)31053-4
Laura J. Yockey
, Luis Varela
, Tasfia Rakib
, William Khoury-Hanold
, Susan L. Fink
, Bernardo Stutz
, Klara Szigeti-Buck
, Anthony Van den Pol
, Brett D. Lindenbach
, Tamas L. Horvath
, Akiko Iwasaki7,
Press enter key to Email the author7Lead Contact
DOI: http://dx.doi.org/10.1016/j.cell.2016.08.004 |
...
Highlights
- •Zika virus replicates in the vaginal tract of wild-type virgin and pregnant mice
- •Innate RNA sensors and type I interferons control vaginal Zika virus replication
- •Vaginal Zika virus infection in early pregnancy leads to fetal growth restriction
- •Vaginal Zika virus infection of pregnant dams leads to fetal brain infection
Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy.
http://www.cell.com/cell/fulltext/S0092-8674(16)31053-4