In the genetic control sequences at the opposite end of the Zika genome, a Musashi Binding Element (MBE) consensus sequence was identified. Musashi-1 and -2 are RNA binding proteins involved in the control of RNA translation, and are often implicated in stem cell replication and differentiation in both developing brain and during spermatogenesis. We were able to document mutations in the MBE region which were acquired and then preserved as the virus moved across the Pacific. Biochemical calculations based on previously published models indicate that these conserved mutations may have altered Musashi protein binding affinity to these sequences, which could help explain some differences in the pattern of human cell infection by the outbreak version of the Zika virus.
So, what’s next? At this point, all our analyses are purely computational, and so the next step is to functionally test the significance of the observations and hypotheses using different viruses, cultured cells, and animal models. In addition, this work is being used by Atheric Pharmaceutical and ioGenetics to help design experiments and interpret a wide range of experimental data, including studies involving human serum samples from patients that have been infected with Zika, and from patients who have developed autoimmune diseases after being infected. The computer predictions are being used to help design Zika vaccine candidates as well as methods for safety testing those candidates. The discoveries from this computer modeling and the analyses are even helping researchers interpret the importance of various mechanisms of action associated with different drugs which inhibit Zika virus replication, and which may be acting in part via Wnt-beta catenin and Notch/Numb signaling – both of which are associated with Musashi regulation.
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Adriano de Bernardi Schneider is a Brazilian biologist and researcher who has been involved in the fight against the Zika virus in the United States since the last epidemic in Brazil in 2015. He acquired a Master of Science degree in Crop Science from the Federal University of Rio Grande do Sul, Brazil in 2012. He is currently pursuing his PhD in Bioinformatics and Computational Biology at UNC Charlotte. His research focuses on evolutionary biology of arboviruses, mainly Zika and Chikungunya viruses. In 2016, he published several studies that have helped advance the understanding of Zika virus evolution. In that same year he, in a joint effort with researchers from Boston, won a series of awards, such as the International Development Innovation Network (IDIN) – MIT – Awardee of Microgrant, for the creation of a mechanism to combat mosquitoes in South America.
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