Recent developments in vertical transmission of ZIKA virus

Recently Zika virus (ZIKV) has been the focus of much attention, primarily because of its association with an increased incidence in microcephaly. Although ZIKV was initially discovered in a sentinel rhesus monkey in Uganda [1], its range includes Africa, Southeast Asia, and Latin America. Much of the recent concern regarding ZIKV arises from a dramatic rise in microcephaly that has been reported in Brazil. However, it is only very recently that definitive scientific evidence has demonstrated the ZIKV as cause of microcephaly. In the past few months there have also been several clinical reports regarding the effect of ZIKV infection on pregnant women and their offspring. A recent study in Rio de Janeiro followed 88 pregnant women of whom 72 tested positive for ZIKV in blood and/or urine by RT-PCR [2] and the timing of infection ranged between 5 and 38 weeks of gestation. Doppler ultrasonography on 42 of ZIKA positive and 16 ZIKA negative subjects revealed fetal abnormalities, including microcephaly and ventricular calcification, in 12 of the 42 ZIKA positive (29%) women who underwent this procedure. Conversely, no fetal abnormalities were detected in 16 ZIKA negative women. In a subsequent report, ZIKV was detected and sequenced from amniotic fluid of two of the patients who had fetuses with microcephaly [3]. Thus, detection of the complete viral genome in the amniotic fluid provides evidence that the virus crosses not only the placental barrier, but also causes microcephaly in significant number of pregnancies. One of the components necessary for the rapid advance of ZIKV research is the availability of a small animal model that faithfully recapitulates the disease process seen in humans. Such a model was developed using mice that lacked type I interferon signaling. Female mice that were Ifnar1-/-were crossed with WT males to produce fetuses that were heterozygous (Ifnar1+/-) [4]. Pregnant dams were inoculated early during embryogenesis (day 6.5 or 7.5) and then sacrificed 7-8 days later. At the time of sacrifice most fetuses had been subject to fetal demise and were reabsorbed. Of those samples that had not undergone fetal demise, viral RNA and infectious virus were detected in the placenta and the fetus, intrauterine growth restriction (IUGR) was also evident and there were apoptotic cells detected in brain samples. Thus, this study established a model which demonstrated in utero transmission of ZIKV along with the pathogenic effects of the virus, such as IUGR and associated damage to …