Recombination of B- and T-cell epitope-rich loci from Aedes- and Culex-borne flaviviruses shapes Zika virus epidemiologyby Gaunt et al.
Findings from this article explain why explosive ZIKV epidemics occurred in DENV-endemic regions of Micronesia, Polynesia and the Americas where Culex-borne flavivirus outbreaks are infrequent, and why ZIKV did not cause major epidemics in Asia where Culex-borne flaviviruses are widespread.
High specificity and sensitivity of Zika EDIII-based ELISA diagnosis highlighted by a large human reference panelby Denis et al.
Researchers developed a ZEDIII-based ELISA that can discriminate between past or current DENV and ZIKV infections, allowing the detection of a serological scar from other flaviviruses. This could be used to confirm exposure of pregnant women or to follow the spread of an endemic disease.
Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathwayby Ferraris et al.
Results from this research show that the differentiation state of hNPCs is a significant factor contributing to the outcome of ZIKV infection and furthermore suggest that ZIKV infection might initiate early activation of the Notch pathway resulting in an abnormal differentiation process, implicated in ZIKV-induced brain injury.
Data in this study suggest that the human upper respiratory tract epithelium is a target for flaviviruses and could potentially play a role in the spread of infection to other body compartments through basolateral virus release. Further work is required to evaluate the risks and define the adapted measures to protect individuals exposed to flavivirus-contaminated body fluids.
Optimization of a fragment linking hit toward Dengue and Zika virus NS5 methyltransferases inhibitorsby Hernandez et al.
A fragment-based drug design approach on flavivirus methyltransferase.
Favipiravir inhibits in vitro Usutu virus replication and delays disease progression in an infection model in miceby Guerrero et al.
This study shows that treatment of mice with favipiravir (150 mg/kg/dose, BID, oral gavage) significantly reduced viral load in blood and tissues and significantly delayed virus-induced disease. The USUV mouse model is amenable for assessing the potential in vivo efficacy of (novel) USUV/flavivirus inhibitors.
Evidence for multiple sylvatic transmission cycles during the 2016–2017 yellow fever virus outbreak, Brazilby Moreira-Soto et al.
Since December 2016, Brazil has experienced an unusually large outbreak of yellow fever (YF). Whether urb a n transmission may contribute to the extent of the outbreak is unclear. The objective of this study was to characterize YF virus (YFV) genomes and to identify spatial patterns to determine thedistribution and origin of YF cases in Minas Gerais, Espírito Santo and Rio de Janeiro, the most affected Brazilian states during the current YFV outbreak.
The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cellsby Bos et al.
In this study researchers show that ZIKV containing BeH819015 structural proteins is much less efficient in cell-attachment leading to a reduced susceptibility ofepithelial A549 and neuronal SH-SY5Y cells to viral infection.
Limited Evidence for Infection of Urban and Peri-urban Nonhuman Primates with Zika and Chikungunya Viruses in Brazilby Moreira-Soto et al.
The authors of this study tested nonhuman primates (NHP) sampled during 2012 to 2017 in urban and peri-urban areas severely affected by ZIKV and CHIKV in Brazil. Seroprevalence and antibody titers were low for both viruses. Additionally, they found evidence for infection by heterologous viruses eliciting cross-reactive antibodies. These data suggest that urban or peri-urban NHP are not easily infected by ZIKV and CHIKV despite intense local transmission, and they may also imply that the ZIKV and CHIKV outbreaks in the Americas cannot be sustained in urban or peri-urban NHP once human population immunity limits urban transmission cycles.
Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerasesby Selisko et al.
In this article, the authors review current knowledge on motifs A-G, defined as the conserved amino-acid sequence strings shared by enzymes, and their role on the structural and mechanistic basis of the fidelity of nucleotide selection and RNA synthesis by Flavivirus RdRps.
Substrate selectivity of Dengue and Zika virus NS5 polymerase towards 2'-modified nucleotide analoguesby Potisopon et al.
In addition to representing the first ZIKV full-length NS5 activity report at the molecular level, this study should help the design of pan-flavivirus drugs aiming at the control of many Flavivirus members of this large family of emerging arboviruses, as well as understand the basis of re-purposing drugs against emerging viral diseases.
The results outlined in the article contribute to a better understanding of the ZIKVMTase, a central player in viral replication and host innate immune response, and lay the basis for the development of potential antiviral drugs.