Novel Genomics Strategies for Clinical Prognosis in Early- Stages of ZIKV Infections: The Search for New ZIKVAssociated Disease Biomarkers

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) belonging to the Flavivirus genus that has quickly become one of the most prominent viral health concerns in recent history. As the global incidence of ZIKV cases grows, so does the concern about its implications for public safety and global spread. In addition to the nonspecific symptoms displayed in ZIKV infections, evidence shows that ZIKV infection can result in more severe pathological outcomes such as microcephaly and Guillain-Barre Syndrome (GBS). Interestingly, the presented symptoms seem to exhibit a geographical population bias, most prominently displayed by the high incidence of ZIKV-associated microcephaly in Brazil. This pathogeographical trend increases the need to consider ZIKV strain variation and host population genomics, as well as existing Flavivirus endemic circulation, as factors contributing to ZIKV-associated health outcomes. To understand the possible complex viral-host interactions involved, a global framework of patient and viral diagnostics must be implemented in areas at risk of, or currently experiencing, endemic Flavivirus circulation. The first step is to develop a simple, cheap, and accurate point-of-care diagnostic for ZIKV. Current diagnostic methods are lacking in sensitivity and/or specificity, a particular issue in areas of co-endemic Flavivirus circulation. Cell-free, paper-based sensors offer a promising means to fulfill this role and even provide discrimination of viral strains at single-base resolution. With the establishment of effective detection and accurate diagnosis of ZIKV infection, the avenue of host and viral diagnostics can be explored using next-generation sequencing technologies to sequence both the host’s and the virus’s genomes. In addition, serological probing in areas of Flavivirus endemicity must be performed, including monitoring for interactions between sequential Flavivirus infections.  A database of this genetic and serological information, along with longitudinal patient monitoring, will provide the necessary basis for linking ZIKV disease severity with genomic causalities and/or previous Flavivirus infections. As patterns emerge, the information can be used in elucidating the mechanistic details of ZIKV pathogenesis and, in the future, open the door to differential treatments based on host genomic susceptibilities as well as particular endemic strain circulation.