This section highlights publications on research conducted by ZIKAlliance consortium members and partners
The findings in this article suggest that the assessment of antibody responses to the identified NS2B epitope is a strong candidate biomarker for the diagnosis and prognosis of Zika-associated neurological disease.
Mathematical modeling substantiated higher seroprevalence of West Niile virus adjacent to an avian migratory route and in areas characterized by forest loss, implying increased risk for zoonotic infections in disturbed areas.
Results of this article show that ZIKV seroprevalence, assessed with two commonly used serological tests, was lower than expected in the cohort of participants who had a confirmed previous ZIKV infection.
This article shows that for reliable serological diagnostics, it is essential to be aware of inherent test limitations and although multiplexed testing and testing of convalescence samples can improve diagnostic performance, global spread of (re-)emerging viruses requires careful implementation and evaluation of serological testing and unambiguous results may not always be achievable.
Pregnant Women Infected with Zika Virus Show Higher Viral Load and Immunoregulatory Cytokines Profile with CXCL10 Increaseby Camacho-Zavala et al.
Results in this paper reveal that the anti-inflammatory response in pregnant women infected with ZIKA is characterized by high CXCL10, a cytokine correlated with congenital malformations.
Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortiaby Ades et al.
This article provides a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia.
This paper finds that Ae. aegypti vector competence for ZIKV from macaques is low, likely to be due to low viral load and the short duration of ZIKV viremia in primates suitable for infecting susceptible mosquitoes.
Influence of Temperature on the Life-Cycle Dynamics of Aedes albopictus Population Established at Temperate Latitudes: A Laboratory Experimentby Marini et al.
Findings in this article highlight the ability of Aedes albopictus to quickly adapt to colder environments and provide new important insights on the bionomics of this species at temperate latitudes.
Zika virus transmission by Brazilian Aedes aegypti and Aedes albopictus is virus dose and temperature-dependentby Chouin-Carneiro et al.
Results indicate that Brazilian populations of Ae. aegypti exhibit a much higher transmission potential for ZIKV than Ae. albopictus.
Contrasted transmission efficiency of Zika virus strains by mosquito species Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from Reunion Islandby Gomard et al.
Our results show that both Ae. albopictus and Ae. aegypti, from Reunion Island, are more likely to be competent for ZIKV in contrast to Cx. quinquefasciatus which appeared refractory to all tested ZIKV strains. This improves our understanding of the role of mosquito species in the risk of the ZIKV emergence on Reunion Island.
Vector Competence of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from Brazil and New Caledonia for Three Zika Virus Lineagesby Fernandes et al.
Viral surveillance and mosquito control measures must be strengthened to avoid the spread of new ZIKV lineages and minimize the transmission of viruses currently circulating.
This is the first report of mosquitoes infected with CHIKV in Iran. The high-throughput screening method here presented can be proposed as a novel epidemiological surveillance tool to identify circulating arboviruses and to support preparedness to an epidemic in animals and humans.
In this study, researchers provide the first demonstration of ZIKV accumulation in the saliva of Cx. pipiens upon forced infection. Nevertheless, they consider Cx. pipiens as a highly inefficient vector for ZIKV.
Researchers have found that ZIKV immunity might be shorter-lived than previously thought, which may contribute to local ZIKV resurgence once individual immune responses wane sufficiently to reduce community protective immunity in addition to birth and migration.
These findings highlight the need to strengthen MAYV surveillance in the region and showcase how modeling can improve interpretation of cross-reacting assays.
The V410L knockdown resistance mutation occurs in island and continental populations of Aedes aegypti in West and Central Africaby Ayres et al.
These results suggest that populations carrying the same kdr mutations may respond differently to the same insecticide, stressing the need for complementary studies when assessing the impact of kdr resistance mechanisms in the outcome of insecticide-based control strategies.
This study demonstrates the circulation of ZIKV in Mali and provides evidence of a previously unidentified outbreak that occurred in the late 1990s.
The invasive Asian bush mosquito Aedes japonicus found in the Netherlands can experimentally transmit Zika virus and Usutu virusby Abbo et al.
Given that Ae. japonicus can experimentally transmit arthropod-borne viruses (arboviruses) like ZIKV and USUV and is currently expanding its territories, we should consider this mosquito as a potential vector for arboviral diseases in Europe.
This analysis confirms the potential of Ae. albopictus as a bridge vector based on its colonization of natural breeding sites in newly invaded areas, its opportunistic feeding behaviour together with the preference for human blood, and the competence to transmit 14 arboviruses.
Survey on Non-Human Primates & Mosquitoes Does not Provide Evidences of Spillover/Spillback between the Urban & Sylvatic Cycles of YFV & ZIKV Following Severe Outbreaks in Southeast Brazilby de Abreu et al.
The present study showed that there is no evidence that the ZIKV established an independent sylvatic cycle in the state of Rio de Janeiro, and provided new evidence that there was no urban transmission of Yellow Fever Virus in southeast Brazil during the current outbreak.
Mapping the response to Zika, a public health emergency, demonstrated a clear pattern of the participation of countries in the scientific advances. The pattern of knowledge production found in this study represented varying country perspectives, research capacity and interests based first on their level of exposure to the epidemic and second on their financial positions regarding science.
Optimisation and field validation of odour-baited traps for surveillance of Aedes aegypti adults in Paramaribo, Surinameby Visser et al.
This study demonstrates that the BG-Sentinel trap baited with the MB5 blend and CO2 outperforms the current golden standard (BG-Sentinel trap with BG-Lure) for monitoring Ae. aegypti females and males, in both laboratory and field experiments. The BG-Bowl baited with the MB5 blend is a good candidate for home use. Finally, the results show that CO2 is an indispensable component of the attractive blend.
Building on the UN’s Sustainable Development Goals commitment to “leave no one behind” and the recent championing of a need for a people-centered approach to epidemic preparedness and response, the authors call for more evidence that can support policy recommendations and advocacy efforts for gender-mainstreamed arbovirus control programs in Latin America.
This study reveals how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. These results might contribute to improving the public health response to outbreaks in Brazil.
The authors review here how viruses, from ancient viruses that integrated the germ line during evolution through old viruses (e.g. papillomaviruses originating from Neanderthals) and more modern sexually-transmitted infections (e.g. simian zoonotic HIV) to emerging viruses (e.g. Ebola and Zika) take advantage of genital tract colonization for horizontal dissemination, viral persistence, vertical transmission and endogenization.
In this study the authors' data provide a convenient and practicable solution to ensure robust differentiation of CHIKV- and MAYV-specific antibodies.
A new class of broadly neutralizing antibodies that target the glycan loop of Zika virus envelope proteinby Qu et al.
Results showed in this article have strong implications for developing anti-ZIKV vaccines and therapeutic mAbs.
Findings in this study highlight the occurrence of the Fort Sherman virus (FSV) across a geographic range exceeding 7,000 km, surprising genomic conservation across a time span exceeding 50 years, M gene‐based reassortment events, and the existence of multiple animal hosts of FSV.
Uncertainty in times of medical emergency: Knowledge gaps and structural ignorance during the Brazilian Zika crisisby Kelly et al.
Uncertainty was a defining feature of the Brazilian Zika crisis of 2015–2016. This article identifies three forms of uncertainty: global health, public health and clinical uncertainty, and it suggests that “emergency research” was effective in tackling global health uncertainty.
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.
Zika seroprevalence declines and neutralizing antibodies wane in adults following outbreaks in French Polynesia and Fijiby Henderson et al.
Data from this study suggest that immunity against the Zika virus may not last as long as previously thought, which could affect the chances of future outbreaks.
Spatiotemporal Analysis of the Population Risk of Congenital Microcephaly in Pernambuco State, Brazilby Alexander et al.
This study emphasizes the burden of microcephaly during the outbreak in Pernambuco, with estimates higher than in some previous studies, and with high risk in an inland region of the state for reasons which are yet to be clarified.
Book chapter in Locating Zika Social Change and Governance in an Age of Mosquito Pandemics; Edited by Kevin Bardosh.
Low vector competence in sylvatic mosquitoes limits Zika virus to initiate an enzootic cycle in South Americaby Fernandes et al.
These results suggest that genetically determined tissue barriers, especially in the midgut, play a vital role in inhibiting ZIKV for transmission in the tested sylvatic mosquito species. Thus, an independent enzootic transmission cycle for ZIKV in South America is very unlikely.
Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortiumby Avelino-Silva et al.
Results of large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV.
This study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.
Based on vector competence data and vector distribution, the auhtors generate a prediction risk map for CHIKV stressing the fear of CHIKV and to a lesser extent, of other arboviruses for Europe, calling us for new public health strategies.
For this study researchers collected nasopharyngeal specimens from 282 children aged ≤5 years with acute respiratory tract infection (ARI) during 2005 to 2006 in one of the largest Brazilian slums.
Results in this study stress the poor ability of Ae. albopictus to sustain a local transmission of ZIKV in Europe and provide a promising tool to evaluate the risk of ZIKV transmission in future outbreaks.
This study reveals distinctive functions of lipin1 and lipin2 in cells of hepatic origin, a context in which they are often considered functionally redundant.
ZIKV cases confirmed by qRT-PCR indicate that the virus was circulating on Curaçao between at least December 2015 and March 2017, and on Bonaire between at least October 2016 and February 2017, with peak cases occurring in November 2016.
Management of insecticide resistance in the major Aedes vectors of arboviruses: Advances and challengesby Dusfour et al.
Based on a plan developed for malaria vectors, here the authors propose some key activities to establish a global plan for insecticide resistance management in Aedes species.
REALM: An Altmetrics-based Framework to Map Science Impacts on Society. A Case Study on Zika Researchby Passos Maia et al.
In this paper the authors describe an altmetrics-based framework which allows the identification of specialists and important research in specific research scenarios.
Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infectionby Zhang et al.
Yeast-derived EDIII is a safe and effective ZIKV vaccine candidate with desirable production traits.
The authors present and show a new tool that can detect endemic and epidemic viruses in different mosquito species in an epidemic context. This fast and low-cost method can be suggested as a novel epidemiological surveillance tool to identify circulating arboviruses.
High specificity and sensitivity of Zika EDIIIbased 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.
Combining genetic crosses and pool targeted DNA‐seq for untangling genomic variations associated with resistance to multiple insecticides in the mosquito Aedes aegyptiby Cattel et al.
This study provides a simple and cost‐effective approach to improve the specificity of resistance allele's detection in multi‐resistant populations while reducing false positives frequently arising when comparing populations showing divergent genetic backgrounds.
Letter to the Editor
Evolution and biological significance of flaviviral elements in the genome of the arboviral vector Aedes albopictusby Houé et al.
Results from this study show a complex association between NIRVS and DENV/CHIKV opening a new avenue for investigating the functional role of NIRVS as antiviral elements shaping vector competence of mosquitoes to arboviruses.
Stable distinct core eukaryotic viromes in different mosquito species from Guadeloupe, using single mosquito viral metagenomicsby Shi et al.
In this article, the authors applied their optimized viral metagenomics protocol (NetoVIR) to compare the virome of single and pooled Aedes aegypti and Culex quinquefasciatus mosquitoes collected from different locations in Guadeloupe, in 2016 and 2017.
ZIKV infection induces robust Th1-like Tfh cell and long-term protective antibody responses in immunocompetent miceby Liang et al.
This study suggests that specific modulation of the Th1-like Tfh cell response during infection or vaccination may augment the induction of antiviral antibody response to ZIKV and other viruses.
In this study, researchers confirmed the association of Anhanga virus (ANHV)‐related viruses with both extant two‐toed sloth species in the Choloepus genus across 3,000 km distance and half a century between the both detections.
This study described a large-scale representative ZIKV seroprevalence study in South America from the recent 2015–2016 Zika epidemic. The findings reveal that the majority of the population remains susceptible to ZIKV, which could potentially allow future reintroductions of the virus.
The authors of this study focus on solutions that address joint temporal and spatial visualization but also consider what the future may bring in terms of visualization and how this may become of value for the coming era of real-time digital pathogen surveillance, where actionable results and adequate intervention strategies need to be obtained within days.
In this study, researchers evaluated the propensity of Aedes aegypti to transmit mechanically Zika virus (ZIKV) using an experimental design.
The results reported in this study suggest that multitypic degnue virus infection may protect from, rather than enhance, development of congenital Zika syndrome.
The results of the present study reveal that the tested Ae. caspius population has a strong midgut escape barrier that limits the dissemination or transmission of the virus. As such, it seems unlikely that European Ae. caspius mosquitoes could be involved in ZIKV transmission if ZIKV was introduced into Europe. This information may help in designing a better strategy to European surveillance and control programmes for ZIKV.
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.
The authors of this study developed two highly sensitive nested RT-PCR assays that cover hot spots of vector adaptation in CHIKV envelope domains. The new assays allow unprecedented molecular surveillance across all CHIKV genotypes and diagnostic use in resource-limited settings globally.
Comparison of Zika virus quantitative reverse transcription PCR results in single timepoint whole blood–plasma pairs from 227 patients with suspected Zika virus infection resulted in confirmation of 8 additional patients with Zika virus infection.
Phylogeography and invasion history of Aedes aegypti, the Dengue and Zika mosquito vector in Cape Verde islands (West Africa)by Salgueiro et al.
The authors of this study performed a phylogeographic and population genetics study of A. aegypti in Cape Verde in order to infer the geographic origin and evolutionary history of this mosquito.
Assessing the Potential Interactions between Cellular miRNA and Arboviral Genomic RNA in the Yellow Fever Mosquito, Aedes aegyptiby Yen et al.
This study shows a broad picture of possible interactions between mosquito cellular miRNAs and the viral RNA of different genotypes/lineages of arboviruses, providing a list of mosquito cellular miRNAs candidates for experimental validations in future studies.
Since the ZIKV outbreak in Brazil in 2015, the scientific community has joined efforts to gather more information on the epidemiology, clinical features and pathogenicity of the virus. Here, we summarize the most important advances made recently and discuss promising, innovative approaches to understand and control ZIKV infection.
Transmission potential of African, Asian and American Zika virus strains by Aedes aegypti and Culex quinquefasciatus from Guadeloupe (French West Indies)by Hery et al.
Culex quinquefasciatus mosquitoes from Guadeloupe are not able to experimentally transmit ZIKV. It was also noticed better transmission of ZIKV strain from Senegal by Ae. aegypti from Guadeloupe compared to Malaysia and Martinique strains.
A computational method for the identification of Dengue, Zika and Chikungunya virus species and genotypesby Fonseca et al.
In this study, the authors developed an efficient method to classify virus sequences with respect to their species and sub-species (i.e. serotype and/or genotype).
This study offers an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.
In this study, the authors explore the potential of antivirals to serve as an effective strategy to prevent sexual transmission. The data illustrate the value of a mouse model to validate the efficacy of new potential ZIKV drugs at the level of the male reproductive system.
Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cellsby Anfasa et al.
In this study, the authors provide in vitro evidence that infection of HUVECs with ZIKV induces apoptosis and elevation of TF expression that leads to activation of secondary hemostasis.
In this review, the authors summarize the results of the evidence to date and elaborate on other possible detrimental effects of cross-reactive flavivirus antibodies, both for ZIKV infection and the risk of ZIKV-related congenital anomalies, DENV infection, and dengue hemorrhagic fever.
This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.
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.
Data provided in this article add important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV.
Zika virus infection among symptomatic patients from two healthcare centers in Sao Paulo State, Brazil: prevalence, clinical characteristics, viral detection in body fluids and serodynamicsby Tozetto-Mendoza et al.
This study shows that urine ZIKV RT-PCR testing in the acute phase of infection can improve the sensitivity of diagnosis, while testing serum is probably less useful despite more sustained shedding in some cases. Higher sensitivity and specificity serological tests are needed for the diagnosis of patients who seek medical attention after the period of ZIKV detection by RT-PCR and for surveillance purposes in settings of high DENV background infection.
Scientific collaboration in Zika: identification of the leading research groups and researchers via social network analysisby Maia et al.
This study shows that a Zika researcher’s influence is basically determined by three factors: (a) number of publications; (b) diversified partnerships; and (c) the links established with the research area’s pioneers.
In this study, the authors determined the global proteomic profile of CHIKV and ZIKV infections in human skin fibroblasts using Stable Isotope Labelling by Amino acids in Cell culture (SILAC)-based mass-spectrometry analysis.
The recent discovery of endogenized elements shows that virus/vector interactions are more dynamic than previously thought, and genetic markers such as NIRVS could be one of the potential targets to reduce arbovirus transmission.
The discovery of the link between ZIKV infection and UPR activation has a broader relevance, since this pathway plays a crucial role in many distinct cellular processes and its induction by ZIKV may account for several reported ZIKV-associated defects.
The authors of this study review the mosquito and vertebrate host species potentially involved in ZIKV vector-borne transmission worldwide; provide an evidence-supported analysis regarding the possibility of ZIKV spillback from an urban cycle to a zoonotic cycle outside Africa; and review hypotheses regarding recent emergence and evolution of ZIKV.
This study highlights the potential of combining traditional surveillance with portable genome sequencing technologies and digital epidemiology to inform public health surveillance in the Amazon region. Data reveal a large CHIKV-ECSA outbreak in Boa Vista, limited potential for future CHIKV outbreaks, and indicate a replacement of the Asian genotype by the ECSA genotype in the Amazon region.
With a low herd immunity in the Vientiane population, ZIKV represents a risk for future large-scale outbreaks. Implementation of a nationwide ZIKV surveillance network and epidemiological studies throughout Laos is needed.
The association between Zika virus infection and microcephaly in Brazil 2015–2017: An observational analysis of over 4 million birthsby Brady et al.
This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate lead the authors to hypothesize that the Northeast region of Brazil was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason.
Correspondence re: Familiar barriers still unresolved - a perspective on the Zika virus outbreak research response
Results obtained in this study suggest that the local transmission of four arboviruses - dengue (DENV), chikungunya (CHIKV), zika (ZIKV) and yellow fever (YFV) viruses - by Ae. albopictus newly introduced in Morocco is a likely scenario.
In Suriname, 770 participants were recruited from 1 urban area and 2 rural villages in the tropical rainforest in order to conduct a ZIKV serosurvey. Researchers found that 35.1% of the participants had neutralizing antibodies against ZIKV. In 1 remote village in the rainforest, 24.5% of the participants had neutralizing antibodies against ZIKV, suggesting that ZIKV was widely spread across the country.
In this study, researchers review recent developments in the understanding of the immune response, with an emphasis on the early antiviral immune response mediated by natural killer cells and emphasize their Janus-faced effects in the control of arbovirus infection and pathogenesis.
Monocyte-Derived Dendritic Cells as Model to Evaluate Species Tropism of Mosquito-Borne Flavivirusesby García-Nicolás et al.
The authors of this study demonstrate Flavivirus-dependent differences in the interaction with monocyte-derived dendritic cells. These may play a role in pathogenesis but appear to only partially reflect the expected species tropism.
Recurrent recent arbovirus infections suggested by serologic data and unspecific symptoms highlight the need for exhaustive virologic testing.
Screening of 533 bats for influenza A viruses showed subtype HL18NL11 in intestines of 2 great fruit-eating bats (Artibeus lituratus). High concentrations suggested fecal shedding.
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.
Combination of ELISA screening and seroneutralisation tests to expedite Zika virus seroprevalence studiesby Nurtop et al.
The authors of this study propose a strategy allowing implementing efficient and practicable large-scale seroepidemiological studies for Zika Virus (ZIKV).
Human stem cell-derived hepatocyte-like cells support Zika virus replication and provide a relevant model to assess the efficacy of potential antiviralsby Tricot et al.
The authors of this study demonstrate that both human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) and the Huh7 hepatoma cell line support the complete ZIKV replication cycle.
Letter to the Editor.
A yellow fever–Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in miceby Kum et al.
The authors of this study report the engineering of a chimeric virus vaccine candidate (YF-ZIKprM/E) by replacing the antigenic surface glycoproteins and the capsid anchor of YFV-17D with those of a prototypic Asian lineage ZIKV isolate.
Researchers report on a class of rhodanine and thiobarbituric derivatives displaying a broad spectrum antiviral activity against seven different enveloped viruses including an HSV-2 acyclovir resistant strain with favorable selectivity indexes.
Potential of Aedes albopictus as a bridge vector for enzootic pathogens at the urban-forest interface in Brazilby dos Santos et al.
Results from this study show that Ae. albopictus frequency declines as it penetrates into the forest and highlight its potential role as a bridge vector of zoonotic diseases at the edge of the Brazilian forests studied.
Researchers have developed and characterized a new in vitro model to study the role of bone development in ZIKV pathogenesis, which will help to identify possible new targets for developing therapeutic and preventive measures.
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.
The authors of this study have identified three major bottlenecks in the implementation of a swift response to the increasing frequency of widespread infectious disease outbreaks: the absence of a timeline for the funding process, delays in regulatory and ethical approval, and the challenging logistics of laboratory support, including diagnostics.
The model provided in this study correctly estimates the number of imported cases and can be easily adapted to other urban areas where Ae. albopictus is the only potential vector present.
Research Models and Tools for the Identification of Antivirals and Therapeutics against Zika Virus Infectionby Alves et al.
This review focuses on the recent advances regarding research models, as well as available experimental tools that can be used for the identification and characterization of potential antiviral targets and therapeutic intervention strategies.
The findings from this study suggest a possible long-term detrimental effect of ZIKV infection on human male fertility that has to be further explored in well-characterized samples from cohort studies conducted in ZIKV-endemic areas.
In the present study, the authors investigate the metabolomic profile of ZIKV-infected microglia.
The findings in this article suggest that the ZIKV epidemic is by and large over within LAC, with incidence projected to be low in most cities in 2018. Local low levels of transmission are probable, but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.
This study provides key insights into how ZIKV may persist in semen and alter semen parameters, as well as a valuable tool for testing antiviral agents.
Differential transmission of Asian and African Zika virus lineages by Aedes aegypti from New Caledoniaby Calvez et al.
The results of this study demonstrate that Ae. aegypti from New Caledonia can become infected and replicate different ZIKV strains belonging to all lineages. These data emphasize the importance of studying the interaction between vectors and their arboviruses according to each local geographic context.
These results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazilby Moreira-Soto et al.
Data from this study support a link between maternal ZIKV infection and congenital malformations and suggest the occurrence of predominantly vector-borne ZIKV transmission in these cases. In addition, some highly prevalent TORCH pathogens may be misinterpreted as representative of ongoing ZIKV activity in the absence of exhaustive diagnostics in northeastern Brazil.
A clinical and histopathological study of malformations observed in fetuses infected by the Zika virusby Beaufrère et al.
The present study reports on the clinical and histopathological findings observed in three fetuses infected by the ZIKV. It emphasizes the severity of brain damages and the minimal visceral and placental changes observed upon ZIKV infection. This confirms the selective neurotropism of ZIKV. Finally, it allows us to describe the cascade of multifactorial developmental defects leading to microcephaly.
Results from this study indicate a low ZIKV transmission by Ae. aegypti and Ae. polynesiensis tested from the Pacific region. These results were unexpected and suggest the importance of other factors especially the vector density, the mosquito lifespan or the large immunologically naive fraction of the population that may have contributed to the rapid spread of the ZIKV in the Pacific region during the 2013–2017 outbreak.
In this study, the authors have traced the phylogenetic history and spatio-temporal dispersal pattern of ZIKV in Asia prior to its explosive emergence in the Pacific region and the Americas.
A Novel Marsupial Hepatitis A Virus Corroborates Complex Evolutionary Patterns Shaping the Genus Hepatovirusby Carneiro et al.
The authors conducted field work in Brazil to sample marsupials, one of the most ancient mammalian lineages, and identified a new HAV, marsupial HAV (MHAV).
The results from this study emphasize the need for continuous quality assessments of Zika virus diagnostic testing globally.
Researchers found no significant association between ZIKV infection and GBS in Bangladesh, but GBS following ZIKV infection was characterized by a distinct clinical and electrophysiological subtype compared to C. jejuni infection. These findings indicate that ZIKV may precede a specific GBS subtype but the risk is low.
For this study, researchers conducted a case-control study focusing on GBS cases in 2014 and retrospectively analyzed 5 years (2011–2015) of GBS in New Caledonia along with arboviruses circulation.
According to the authors, SuPReMe, therefore, represents an effective and promising option for the rapid generation of clonal recombinant populations of single-stranded positive-sense RNA viruses.
The risk of congenital neurologic defects related to Zika virus (ZIKV) infection has ranged from 6 to 42% in various reports. The aim of this study was to estimate this risk among pregnant women with symptomatic ZIKV infection in French territories in the Americas.
The authors conclude that ZIKV has been circulating in Bolivian tropical areas but not in highlands, and that the epidemic has not be en limited by previous immunity against dengue. Specific attention should be paid to the region of Santa Cruz, where the seroprevalence is still limited, but the density of Aedes aegypti populations makes plausible further spreading of the disease.
According to the authors of this study, mosquito control measures should remain focused on the mosquito Ae. aegypti which is also the vector of CHIKV and DENV, and much more research effort should be allocated to fill the knowledge gaps about this virus.
A novel hepatitis B virus species discovered in capuchin monkeys sheds new light on the evolution of primate hepadnavirusesby Souza et al.
Data in this article suggest ancestral co-speciation of hepadnaviruses and NHP, and an Old World origin of the divergent HBV genotypes F/H. The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B.
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 Polymerases
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.
The findings of this study have implications for the development of multifaceted infection control programs, including strategies for prevention and awareness, helping the population to develop an accurate perception of the threat they are facing and encouraging behavior changes.
The authors of this study discuss gaps in the knowledge and the challenges ahead to anticipate, prevent, and control emerging and re-emerging epidemics of arboviruses in Brazil and worldwide.
Recombinant Zika NS1 Protein Secreted from Vero Cells Is Efficient for Inducing Production of Immune Serum Directed against NS1 Dimerby Viranaicken et al.
The authors of this article demonstrated that recombinant ZIKV NS1 expressed in mammalian cells stably transduced with a lentiviral vector is suitable for inducing the production of specific antibody directed against NS1 oligomer. According to the authors, anti-ZIKV immune serum could be a great tool for the specific detection of secreted NS1 hexamer in human cells infected with ZIKV of African and Asia lineages, including contemporary epidemic strains.
In this study, researchers assessed for the first time the venereal transmission of ZIKV between Aedes aegypti under laboratory conditions. Their conclusion is that venereal transmission between Aedes mosquitoes might contribute to Zika virus maintenance in nature.
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.
Infection of a French Population of Aedes albopictus and of Aedes aegypti (Paea Strain) with Zika Virus Reveals Low Transmission Rates to These Vectors’ Salivaby Ryckebusch et al.
This study shows that the extrinsic incubation period of Ae. aegypti for transmission is shorter than that of Ae. albopictus.
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.
The authors of this study found that Culex quinquefasciatus does not support ZIKV replication and Wolbachia is not involved in producing this phenotype. These mosquitoes are therefore very unlikely to play a role in transmission of ZIKV.
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.
Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategiesby Best et al.
Researchers found that in order for an antiviral treatment to effectively reduce the time to plasma viral clearance therapy should be initiated at the time of infection or given prophylactically.
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.
Researchers demonstrate that strategically combining the suppression methods with Wolbachia can generate a sustained control while mitigating the risks of inadvertent exacerbation of the wild mosquito population.
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.