1. Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection
- Author
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Susan L. Fink, Luis Varela, Brett D. Lindenbach, William Khoury-Hanold, Anthony N. van den Pol, Bernardo Stutz, Klara Szigeti-Buck, Akiko Iwasaki, Laura J. Yockey, Tamas L. Horvath, and Tasfia Rakib
- Subjects
0301 basic medicine ,Abortion, Habitual ,030106 microbiology ,Receptor, Interferon alpha-beta ,Virus Replication ,Article ,General Biochemistry, Genetics and Molecular Biology ,Zika virus ,Mice ,03 medical and health sciences ,Pregnancy ,Interferon ,medicine ,Animals ,Pregnancy Complications, Infectious ,Brain Diseases ,Fetus ,Fetal Growth Retardation ,biology ,Zika Virus Infection ,Brain ,Zika Virus ,biology.organism_classification ,medicine.disease ,Virology ,Mice, Mutant Strains ,3. Good health ,Mice, Inbred C57BL ,Disease Models, Animal ,Flavivirus ,030104 developmental biology ,medicine.anatomical_structure ,Viral replication ,Vagina ,Immunology ,IRF7 ,Female ,Interferon Regulatory Factor-3 ,medicine.drug - Abstract
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.
- Published
- 2016