Zika virus (ZIKV) infection has emerged as a global health threat and infection of pregnant women causes intrauterine growth restriction, spontaneous abortion and microcephaly in newborns. Here we show using biologically relevant cells of neural and placental origin that following ZIKV infection, there is attenuation of the cellular innate response characterised by reduced expression of IFN-β and associated interferon stimulated genes (ISGs). One such ISG is viperin that has well documented antiviral activity against a wide range of viruses. Expression of viperin in cultured cells resulted in significant impairment of ZIKV replication, while MEFs derived from CRISPR/Cas9 derived viperin−/− mice replicated ZIKV to higher titers compared to their WT counterparts. These results suggest that ZIKV can attenuate ISG expression to avoid the cellular antiviral innate response, thus allowing the virus to replicate unchecked. Moreover, we have identified that the ISG viperin has significant anti-ZIKV activity. Further understanding of how ZIKV perturbs the ISG response and the molecular mechanisms utilised by viperin to suppress ZIKV replication will aid in our understanding of ZIKV biology, pathogenesis and possible design of novel antiviral strategies.

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks’ gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99–1.44)) or who had lower selenium concentrations (1.19 (1.01–1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06–2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.

Single nucleotide polymorphisms and pre-and peri-conception folic acid (FA) supplementation and dietary data were used to identify one-carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 μg daily FA at 15-week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 μg (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L −1 vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre-and early-pregnancy dietary factors, are independent risk factors for pregnancy complications.

Not applicable.