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.
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.
Letter to the Editor
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.
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.
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.
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.
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
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.
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.
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
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.
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.
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.
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.
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.
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 been 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.
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.
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.
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.
High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks [Press Release]by ZIKAlliance
A study published this week in mBio demonstrates rapid spread of ZIKV in Salvador, a metropolis in northeastern Brazil representing one of the most affected areas during the American ZIKV outbreak, and infection rates exceeding 60%.
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.
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.
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.
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.
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. These data show that this compound 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.
The key message from this study 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 the authors needed to make in the absence of good data 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.
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.