Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection and provide the first consistent ZIKV-associated phenotype in macaques for testing medical countermeasures. Author summaryThe 2016 Zika virus (ZIKV) pandemic revealed a risk of birth defects associated with in-utero exposure to Asian-lineage ZIKV. Less is known about the impacts of African-lineage ZIKV infection during pregnancy, although it has been shown to cause adverse pregnancy outcomes in small animal models. Here we provide evidence that ZIKV infection early in the first trimester caused a high rate (78%) of pregnancy loss in rhesus macaques. These findings suggest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection and provide the first consistent ZIKV-associated phenotype in macaques for testing medical countermeasures.