Zika Research Shifts into High Gear

The number of scientific articles mentioning Zika virus has nearly doubled in the past two months, a testament to both the intensity of ongoing efforts to expose its secrets and how far under the radar Zika had been prior to the current epidemic. With the biomedical research enterprise now in full swing, what are the latest advances and what new avenues are these findings opening up? First off, thanks to the efforts of Sirohi et al. (2016), we now have a detailedmugshot of the perpetrator. This comes in the form of a 3.8 Å resolution structure determined by cryoelectron microscopy of a strain from the 2013–2014 French Polynesia outbreak (very closely related to those currently spreading throughout the Americas). What does it look like? Like other flaviviruses, such as dengue, the mature Zika virus is enveloped with an icosahedral shell that has 180 copies each of the envelope glycoprotein andmembrane protein assembled in 90 dimeric heterodimers. Although it is grossly similar to dengue, the most notable differences in structure arise around Asn154 in the envelope protein, which harbors Zika’s sole glycosylation site. In dengue, both the cognate site (Asn153) and another site (Asn67) are glycosylated, and it is the latter that mediates the envelope glycoprotein’s interaction with DC-SIGN, a C-type lectin receptor that serves as one of the entry receptors for the virus. Is the region around Asn153 important for Zika’s unique effects, in particular for its apparent neurotropism? Interestingly, glycosylation of Asn154 in West Nile virus has been previously suggested to play a role in neural invasion. Future work will explore this potential link, which should be aided by emerging insights into Zika’s entry receptors.