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Articles

This section highlights publications on research conducted by ZIKAlliance consortium members and partners

The remarkable efficacy of the ClearColi BL21(DE3)-based expression system at eliciting the rapid production of specific anti-ZIKV antibodies endorses an innovative method, which can be extended to emerging viruses for which development of immunological tools is an urgent prerequisite.

Results from this study suggest that despite the inter-individual variability in immune responses, the magnitude of the maternal ZIKV-specific neutralizing antibody response may prove useful to corroborate congenital ZIKV infection, contributing to reliable estimates of the manifestation index of ZIKV-associated congenital disease. Further studies will be needed to evaluate the time-course of maternal neutralizing antibody responses to identify whether a high maternal PRNT titer can be used as an early marker of congenital infection aiding potential antiviral intervention strategies.

In this work, the authors analysed the transmission dynamics of the Wynwood outbreak, recorded in Florida at the end of July 2016, using a mathematical model calibrated to outbreak data, and assessed the efficacy of the implemented vector control measures in containing viral transmission. Results from this analysis provide useful insights for prevention and control of possible future outbreaks in European areas.

In this letter, the authors address the need for curation and standardized annotation of ZIKV reference genomes in order to guide researchers and clinicians in genomic analyses and the translation of research findings.

This study demonstrates for the first time that motor neurons support ZIKV replication and these cells are as a consequence of ZIKV replication destroyed by the virus, and that human iPSC derived neuronal cells offer a physiologically relevant system to assess the potential antiviral effect of small molecule inhibitors of viral replication that are being developed to clear ZIKV infections in the nervous system.

Researchers have demonstrated that the recent ZIKV outbreak in Latin America substantially affects the DENV serology in routine diagnostic laboratories.

Results from this study indicate that bats do not sustain sufficient virus amplification in order to function as reservoirs and exclude them as players in the dengue virus transmission cycle.

Taken together, this study shows that African and Asian ZIKV strains differ in their abilities to infect and replicate in different neural cells, as well as their abilities to cause cell death early after infection. This implies that caution is necessary against extrapolation of experimental data obtained using historical African ZIKV strains to the current outbreak. In addition, the fact that Asian ZIKV strains infect only a minority of cells with a relatively low burst size together with the lack of early cell death induction might contribute to their ability to cause chronic infections within the CNS.

This study showed the up-regulation of several detoxification genes of multiple enzyme families associated with metabolic resistance, and the presence of the two kdr mutations, with the F1534C being fixed. Another suggested mechanism probably involved in the resistance phenotype is cuticle thickening, as several cuticle genes were found overexpressed. This study reinforces the importance of alternative control strategies to suppress Ae. aegypti population and thus reduce the likelihood of arbovirus transmission in the region.

Results from this study further indicate that viruses from northeast Brazil were important for the continental spread of ZIKV. Within Brazil, the authors find instances of virus lineage movement from northeast to southeast Brazil; most of these events are dated to the second half of 2014 and led to onwards transmission in Rio de Janeiro and São Paulo states. The authors infer that ZIKV lineages disseminated from northeast Brazil to elsewhere in Central America, the Caribbean, and South America.

The study shows that Culex quinquefasciatus should not be considered a potential vector of ZIKV in Brazil.

This study shows that imipramine strongly inhibits the replication of several Flaviviridae family members, including Zika, West Nile and Dengue virus. Data show that imipramine is a potential drug candidate for anti-arboviral treatment.

The findings from this study indicate that the immunity of the Cameroonian population against ZIKV is low and that circulation in urban populations is uncommon. Hence, the risk of epidemic spread of ZIKV does exist. The virus is likely to be imported by infected travelers coming from epidemic areas and has the potential to be transmitted by local peri-domestic mosquitoes. This study provides biological evidence that such introduction would occur in populations that are globally immunologically naïve against ZIKV infection and live in areas where potential epidemic vectors exist.

The authors of this article describe inhibition of ZIKV replication by suramin, originally an anti-parasitic drug. They suggest that the inhibitory effect of suramin on ZIKV attachment and virion biogenesis and its broadspectrum activity warrant further evaluation of this compound as a potential therapeutic.

Based on the reported data from Brazil in 2015/16, this publication describes a plausible range for the risk of microcephaly in women who were infected with Zika virus during pregnancy compared to those who were not infected. The key message is that the large uncertainty around the risk estimate needs to be further investigated because of a) the possible existence of co-factors that are yet to be validated, b) the assumptions that need be made for the proportion of women who were infected during pregnancy.

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.

The article concludes that infection with Flaviviridae can increase centrosome numbers and impair spindle positioning, thus potentially contributing to microcephaly in the case of Zika.

This study describes for the first time the specific antiviral gene expression in infected primary human astrocytes, the major glial cells within the central nervous system.

This pioneering study suggests that the study of blood donors during outbreaks of emerging pathogens has become a key element of epidemiological surveillance.

This study highlights the dual role of Axl during ZIKV infection of glial cells: promoting viral entry and modulating innate immune responses. Therefore, inhibiting Axl function may represent a potential target for future antiviral therapies.

By using the bacterium-free ‘Infectious Subgenomic Amplicons’ (ISA) method, this study provides the scientific community with two simple and performing reverse genetics systems for ZIKV.

The article argues that the off-label use of drugs that may protect against Zika virus-induced brain damage has to be balanced with their risk during pregnancy.