This section highlights publications on research conducted by ZIKAlliance consortium members and partners
In this study, by adding 13 new full ZIKAV genome sequences, isolated from different places in the Pacific region and at different periods of time, along with other published genomes, the authors provide for the first time a map of the whole ZIKAV Pacific sublineage, from the Western to the Eastern edges of the Pacific ocean.
In order to understand the mechanism of Zika virus-associated microcephaly, the authors combined analysis of human fetuses infected with Zika virus, cultures of human neuronal stem cells and mice embryos. They showed that ZIKV infection of cortical progenitors controlling neurogenesis triggers a stress in the endoplasmic reticulum in the embryonic brain, inducing signals in response to incorrect protein con-formation.
The authors performed an experimental oral infection with the Asian genotype of ZIKV in Ae. albopictus from La Réunion and found a strong midgut barrier to dissemination. This result is discussed in the light of previous vector competence assays for DENV and CHIKV performed on other Ae. albopictus populations from La Réunion.
High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaksby Netto et al.
In this article, authors find that the high burden of Zika virus infection in a northeastern Brazilian metropolis questions the fate of the outbreak due to population protective immunity; that Zika virus infection predominantly affects geographic areas with low socioeconomic status, demonstrating a clear link between poverty and Zika virus infection; and, finally, additional evidence for the link between Zika virus infection and microcephaly.
In 2015–2016 in the Recife Metropolitan Region, the authors of this study detected the tail end of a Zika epidemic, which was displaced by a chikungunya epidemic. Few dengue cases were identified despite a high number of official dengue notifications in the area during this period. This study shows here important epidemiological features of these cases.
In order to overcome potential technological issues related to the study of arboviruses, the authors of this study designed an improved DNA transfection protocol for insect cells and then demonstrated that the simple and flexible ISA (Infectious Subgenomic Amplicons) reverse-genetics method can be efficiently applied to both mammalian and mosquito cells to generate in days recombinant infectious positive-stranded RNA viruses belonging to genera Flavivirus (Japanese encephalitis, Yellow fever, West Nile and Zika viruses) and Alphavirus (Chikungunya virus).
The authors of this study developed novel multiplex real-time reverse transcription PCRs. The new PCRs enable yellow fever (YFV) detection with diagnostic sensitivity. Although the dual-target assay is superior to the single-target assay in sensitivity and robustness to target competition, the single-target assay – as stated by the researchers – may be advantageous in resource-limited settings and may be more convenient for multiplex usage in combination with assays targeting co-circulating arboviruses, such as chikungunya, Zika, and dengue viruses.
Results from this study suggest that ZIKV has mechanisms to evade mosquito innate immunity and it is therefore important to understand virus-vector interactions and the implications they have on transmission.
ClearColi BL21(DE3)-based expression of Zika virus antigens illustrates a rapid method of antibody production against emerging pathogensby Viranaicken et al.
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.
Evidence for congenital Zika virus infection from neutralizing antibody titers in maternal sera, north-eastern Brazilby Moreira-Soto et al.
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.
Replication of the Zika virus in different iPSC-derived neuronal cells and implications to assess efficacy of antiviralsby Lanko et al.
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.
Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cellsby Anfasa et al.
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.
Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal)by Seixas et al.
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.
In this study, the authors select examples of (re)emerging pathogenic arboviruses and explain the reasons for their emergence and different patterns of dispersal, focusing particularly on the mosquito vectors which are important determinants of arbovirus emergence. They also attempt to identify arboviruses likely to (re)emerge in the future.
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.
Culex quinquefasciatus from areas with the highest incidence of microcephaly associated with Zika virus infections in the Northeast Region of Brazil are refractory to the virusby Fernandes et al.
The study shows that Culex quinquefasciatus should not be considered a potential vector of ZIKV in Brazil.
Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Traffickingby Wichit et al.
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.
Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particlesby Albulescu et al.
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.
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.
This study showcases the contribution of modeling to inform local health-care planning during an outbreak. Timely studies that estimate the proportion of infected persons that seek care are needed to improve the predictive power of such approaches.
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.
African and Asian Zika virus strains differentially induce early antiviral responses in primary human astrocytesby Hamel et al.
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.
Based on comparative ZIKV complete genome phylogenetic analyses and temporal estimates, the authors identify amino acid substitutions that may be associated with increased viral epidemicity, CZVS, and GBS. Reverse genetics, vector competence, and seroepidemiological studies will test the hypothesis that these amino acid substitutions are determinants of epidemic and neurotropic ZIKV emergence.