Zika as a flavivirus causing microcephaly in newborns is no longer falling in the realm of suppositions. The virus’ link to the condition now appears to be rather robust and as such regarded by WHO and other research and regulatory bodies.Citation1, 2 Epidemiological, virological, and clinical evidence for the strength of the link is well reviewed and critically discussed in a paper published in this issue of the Journal (see Ticconi et al.),Citation3 an issue that also contains an interesting report on the evolutionary analysis and predictions on T–B cells epitope of viral proteins in Zika (see Angeletti et al.).Citation4 While further data on Zika causality in other neurological disorders (e.g. Guillain–Barrè syndromeCitation5) and transmission patterns (particularly regarding sexual transmissionCitation6) are needed, research is now expanding to gain insights into the mechanisms whereby Zika infects and damages the brain as well as ways of effectively fighting the virus to protect against the disease(s) it causes.
One question that remains open is how the virus crosses the placental barrier and reaches the fetus brain in the presence of inhibitory and virus reproduction non-permissive tissue barriers isolating the fetus from its mother. Migrating ‘carriers’ of the macrophage type were suspected based on previous data with dengue virus, and indeed some placental macrophages and fibroblasts in the placental villi can be productively infected by Zika virus.Citation7 Concerning brain damage, Dang and collaboratorsCitation8 using human embryonic stem cell-derived cerebral organoids have shown a size restriction of this organoid associated with Zika reproduction. They introduce a potential role of innate immunity activation through the Toll-like receptor 3 in neurogenesis disruption, a suggestion in line with a previous report by others using a different model.Citation9
The increasing evidence for a Zika/microcephaly connection and possible involvement of this virus in other diseases drives vaccine research despite the well-known obstacles for achieving it, as mentioned elsewhere.Citation10 Yet these obstacles have not discouraged the studying and implementation of several vaccine approaches, including DNA vaccines. Some vaccine formulations are reported to be undergoing clinical trials by the end of this year.Citation11 A critical aspect of this research is obviously establishing mechanisms and potential correlates of protection. In this context, of interest are the recent reports about the existence of potent neutralizing antibodies,Citation12,13 some of which are cross-reactive with dengue virus antigens and present in dengue-infected patients. The existence of a conserved epitope in dengue and Zika viruses also suggests the possibility of generating a universal vaccine protecting against a group of flavivirus.Citation13
Overall, the scientific and public health community is effectively responding to the Zika challenge, with a positive perspective toward the generation of knowledge and weapons able to attenuate if not abate our concerns about this emerging, yet poorly known virus. It is hoped that this ‘call to arms’ against Zika will not detract from enhanced attention to other dreadful, constantly impending, microbial threats.Citation10
Polo d'innovazione della genomica, genetica e biologia, Università di Perugia, Perugia, Italy
[email protected]
References
- Pan American Health Organization, World Health Organization. World Health Organization. Epidemiological Alert: neurological syndrome, congenital malformations, and Zika virus infection. Implications for Public Health in the Americas. Washington, DC: World Health Organization, Pan American Health Organization; December 1, 2015.
- European Centre for Disease Prevention and Control. Rapid risk assessment: Zika virus epidemic in the Americas: potential association with Microcephaly and Guillain-Barrè Syndrome. Second Update, 8 February 2016. Stockholm: ECDC; 2016.
- Ticconi C, Pietropolli A, Rezza G. Zika virus infection and pregnancy: what we do and do not know. 2016;1–7. doi:10.1080/20477724.2016.1234804.
- Angeletti S, Presti AL, Giovanetti M, Grifoni A, Amicosante M, Ciotti M, et al. Phylogenesys and homology modeling in Zika virus epidemic: food for thought. 2016;1–6. doi:10.1080/20477724.2016.1235337.
- Muñoz LS, Barreras P, Pardo CA. Zika virus-associated neurological disease in the adult: Guillain-Barré syndrome, encephalitis, and myelitis. Semin Reprod Med. 2016;43:273–279.
- Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL, Stutz B, et al. Vaginal exposure to Zika virus during pregnancy leads to fetal brain infection. Cell. 2016;166:1247–1256.10.1016/j.cell.2016.08.004
- Jurado KA, Simoni MK, Tang Z, Uraki R, Hwang J, Householder S, et al. Zika virus productively infects primary human placenta-specific macrophages. JCI Insight. 2016;181. doi:10.1172/jci.insight.88461.
- Dang J, Tiwari SK, Lichinchi G, Qin Y, Patil VS, Eroshkin AM, et al. Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell. 2016;19:258–265.10.1016/j.stem.2016.04.014
- Garcez PP, Loiola EC, Madeiro da Costa R, Higa LM, Trindade P, Delvecchio R, et al. Zika virus impairs growth in human neurospheres and brain organoids. Science. 2016;352:816–818.10.1126/science.aaf6116
- Cassone A. Zika, more reasons for concern. Pathog Glob Health. 2016;110:37–38.10.1080/20477724.2016.1182803
- Durbin AP. Vaccine development for Zika virus-timelines and strategies. Semin Reprod Med. 2016;34:299–304.
- Swanstrom JA, Plante JA, Plante KS, Young EF, McGowan E, Gallichotte EN, et al. Dengue virus envelope dimer epitope monoclonal antibodies isolated from dengue patients are protective against Zika virus. mBio. 2016;7:e01123-16.
- Barba-Spaeth G, Dejnirattisai W, Rouvinski A, Vaney MC, Medits I, Sharma A, et al. Structural basis of potent Zika-dengue virus antibody cross-neutralization. Nature. 2016;536:48–53.10.1038/nature18938