Zika Virus Research Articles

Geographic Distribution and Temporal Trends of Zika Virus Outbreaks in India (2016-2023): Insights From the Integrated Disease Surveillance Programme Data.

Introduction This study examines the geographic distribution and temporal trends of Zika virus (ZIKV) outbreaks in India from 2016 to 2023 using data from the Integrated Disease Surveillance Programme (IDSP). The burden of ZIKV in India has risen due to its rapid spread and significant health impacts. Existing literature highlights seasonal and geographic patterns but lacks a comprehensive, long-term analysis specific to India. This study addresses this gap by analyzing trends over seven years to inform better public health responses. Methods A secondary data analysis was conducted using publicly available data from the IDSPon reported Zika cases from January 2016 to December 2023. Descriptive statistical methods and geographic information system(GIS) mapping techniques were employed to analyze the geographic distribution and temporal trends of ZIKVoutbreaks in India. The data were analyzed and visualized using R software version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria), with heat maps and choropleth maps to identify hotspots, and line diagrams to identify temporal trends. Results Zika outbreaks predominantly occurred during the post-monsoon season, accounting for 47.62% (n= 10) of the total 21 outbreaks, followed by the monsoon season with 33.33% (n = 7), and summer with 19.05% (n = 4). Two deaths were reported during a significant outbreak in Madhya Pradesh in 2018. Temporal trends indicated notable spikes in cases in 2018 (131 cases) and 2021 (234 cases), with no cases reported in 2019 and 2020. The geographic distribution maps highlighted significant concentrations of ZIKV outbreaks in specific districts within Uttar Pradesh, Madhya Pradesh, and Kerala. Discussion The study identified seasonal patterns, with most cases occurring in the post-monsoon season. The geographic spread of the ZIKV was observed in eight states from 2016 to 2023. GIS identified three hotspots in Uttar Pradesh, Madhya Pradesh, and Kerala. Conclusion The study highlights the need for heightened surveillance and targeted intervention preparedness during high-risk seasons. Enhancing testing facilities and data reporting systems could improve outbreak identification, management, and response.

The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.

Flaviviruses, including dengue (DENV), Zika (ZIKV), West Nile (WNV), Japanese encephalitis (JEV), yellow fever (YFV), and tick-borne encephalitis (TBEV) viruses, pose a significant global emerging threat. With their potential to cause widespread outbreaks and severe health complications, the development of effective vaccines and antiviral therapeutics is imperative. The flaviviral non-structural protein 5 (NS5) is a highly conserved and multifunctional protein that is crucial for viral replication, and the NS5 protein of many flaviviruses has been shown to be a potent inhibitor of interferon (IFN) signalling. In this review, we discuss the functions of NS5, diverse NS5-mediated strategies adopted by flaviviruses to evade the host antiviral response, and how NS5 can be a target for the development of vaccines and antiviral therapeutics.

Picetannol and naringenin effects in Zika virus infected HTR-8/SVneo cells

Picetannol and naringenin effects in Zika virus infected HTR-8/SVneo cells

Zika virus infection alters the biomechanical and biochemical properties of extravillous trophoblast cells

Zika virus infection alters the biomechanical and biochemical properties of extravillous trophoblast cells

Protective effects of the ethanolic extract from Passiflora edulis seeds against Zika virus infection in human HTR-8/SVneo cells

Protective effects of the ethanolic extract from Passiflora edulis seeds against Zika virus infection in human HTR-8/SVneo cells

The Impact of Zika Emergence in Remote Communities in Northwestern Ecuador.

The Zika virus (ZIKV) epidemic in Latin America (2015-2016) has primarily been studied in urban centers, with less understanding of its impact on smaller rural communities. To address this gap, we analyzed ZIKV seroepidemiology in 6 rural Ecuadorian communities (2018-2019) with varying access to a commercial hub. Seroprevalence ranged from 19% to 54%, measured by nonstructural protein 1 blockade of binding enzyme-linked immunosorbent assay. We observed a decline in ZIKV seroprevalence between 2018 and 2019 that was greater among younger populations, suggesting that the attack rates in the 2015-2016 epidemic were significantly higher than our 2018 observations. These data indicate that the 2015-2016 epidemic included significant transmission in rural and more remote settings. Our observations of high seroprevalence in our area of study highlights the importance of surveillance and research in rural areas lacking robust health systems to manage future Zika outbreaks and vaccine initiatives.

Self-Perceived Quality of Life (WHOQOL-Bref), and Self-Reported Health, Social and Environmental Factors Related to Its Improvement among Residents of Anil, Rio de Janeiro-Cross-Sectional Study.

This study aims to assess the self-perception of the QoL (WHOQOL-bref) in the Canal of Anil zone and its neighbor zone of the center of the District of Anil in Rio de Janeiro and to identify which factors are associated with the population self-perception of the need to "improve" their quality of life (QoL). A cross-sectional observational analytical study was carried out after approval by the competent ethics committee (CEP/CONEP) approval. A non-probabilistic sampling of residents of the Canal of Anil (n = 494) and the central district of Anil (n = 250) was used. A questionnaire was administered in person to collect data on self-reported sociodemographic characteristics, general health, sanitation, lifestyle in the residential area, and the WHOQOL-Bref. Although with a worse self-perceived water/sanitation participants in the Anil Canal community report fewer allergies, less medication, fewer skin diseases, less Zika virus, and less Chikungunya, among others. The self-perception of the need to improve the QoL in the Anil Canal community and the zone at the central District of Anil has proved to be influenced by several social and economic factors as well as residential practices and conditions. The multivariate analysis allowed us to identify both modifiable and non-modifiable risk factors for the need to improve physical QoL: taking medication, respiratory problems, skin disease diagnosed by a doctor, having a water tank at home or having filtered water at home, unpleasant odor of the water of the Anil Canal and the level of education, and age. Regarding the need to improve the environmental QoL, both areas are largely modifiable (e.g., having had ascariasis/roundworm; having a water tank in the house; not drinking bottled water; not having pavements in the street). Sociodemographic and environmental factors, in addition to health conditions, play a pivotal role in influencing individuals' perceptions of the necessity for enhanced physical and environmental well-being.

Is cross-species horizontal gene transfer responsible for gallbladder carcinogenesis

BackgroundCross-species horizontal gene transfer (HGT) involves the transfer of genetic material between different species of organisms. In recent years, mounting evidence has emerged that cross-species HGT does take place and may play a role in the development and progression of diseases.MethodsTranscriptomic data obtained from patients with gallbladder cancer (GBC) was assessed for the differential expression of antisense RNAs (asRNAs). The Basic Local Alignment Search Tool (BLAST) was used for cross-species analysis with viral, bacterial, fungal, and ancient human genomes to elucidate the evolutionary cross species origins of these differential asRNAs. Functional enrichment analysis and text mining were conducted and a network of asRNAs targeting mRNAs was constructed to understand the function of differential asRNAs better.ResultsA total of 17 differentially expressed antisense RNAs (asRNAs) were identified in gallbladder cancer tissue compared to that of normal gallbladder. BLAST analysis of 15 of these asRNAs (AFAP1-AS1, HMGA2-AS1, MNX1-AS1, SLC2A1-AS1, BBOX1-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1-AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS) showed varying degree of similarities with bacterial and viral genomes, except for UNC5B-AS1 and SOX21-AS1, which were conserved during evolution. Two of these 15 asRNAs, (VPS9D1-AS1 and SLC2A1-AS1) exhibited a high degree of similarity with viral genomes (Chikungunya virus, Human immunodeficiency virus 1, Stealth virus 1, and Zika virus) and bacterial genomes including (Staphylococcus sp., Bradyrhizobium sp., Pasteurella multocida sp., and, Klebsiella pneumoniae sp.), indicating potential HGT during evolution.ConclusionThe results provide novel evidence supporting the hypothesis that differentially expressed asRNAs in GBC exhibit varying sequence similarity with bacterial, viral, and ancient human genomes, indicating a potential shared evolutionary origin. These non-coding genes are enriched with methylation and were found to be associated with cancer-related pathways, including the P53 and PI3K-AKT signaling pathways, suggesting their possible involvement in tumor development.

Impact of Zika virus non-structural protein mutations on hippocampal damage.

Impact of Zika virus non-structural protein mutations on hippocampal damage.

In Vitro Antiviral Activity of Rhodiola crenulata Extract against Zika Virus and Japanese Encephalitis Virus: Viral Binding and Stability.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) can cause permanent neurological damage and death, yet no approved drugs exist for these infections. Rhodiola crenulate, an herb used in traditional Chinese medicine for its antioxidation and antifatigue properties, was studied for its antiviral activity against ZIKV and JEV in vitro. The cytotoxicity of Rhodiola crenulata extract (RCE) was evaluated using the CCK-8 reagent. Antiviral effects of RCE were assessed in ZIKV-infected or JEV-infected Vero cells via quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, fluorescent focus assay (FFA), and immunofluorescence assay (IFA). The cell-free antiviral effects of RCE were evaluated using an inactivation assay. To determine the stage of the viral life cycle affected by RCE, time-of-addition, binding, and entry assays were conducted. Three bioactive constituents of RCE (salidroside, tyrosol, and gallic acid) were tested for antiviral activity. RCE exhibited dose-dependent anti-ZIKV and anti-JEV activities at non-cytotoxic concentrations, which were likely achieved by disrupting viral binding and stability. Gallic acid exhibited antiviral activity against ZIKV and JEV. Our findings indicate that RCE disrupts viral binding and stability, presenting a potential strategy to treat ZIKV and JEV infections.

The total synthesis of Wulfenioidin F

Zika virus, an RNA virus that can cause severe damage to the human body, has long lacked an effective drug. Scientists have discovered recently that Wulfenioidin, a plant distributed in southern China, contains a compound in its root that holds the potential to become an anti-Zika drug. Through extraction, multiple kinds of Wulfenioidin were discovered and their structures were characterized through various spectroscopic methods. However, there isnt a total synthesis pathway for Wulfenioidin. This essay focuses on Wulfenioidin F and provides a full synthesis pathway for the molecule. The route begins with the synthesis of two fragments 6-(2-bromo-6-methylphenyl)-6-methoxy-2-methylhexan-2-ol and 5-(propan-2-yl)-3-(I^5-diazynylidene)-3,4-dihydro-2H-pyran-2,4-dione, which then undergo a convergent coupling to form an eight-carbon ring. An intermolecular Diels-Alder reaction combines the benzyne and pyrone together, forming the final product and completing the total synthesis.

The Role of TIM-1 and CD300a in Zika Virus Infection Investigated with Cell-Based Electrical Impedance.

Orthoflaviviruses cause a major threat to global public health, and no antiviral treatment is available yet. Zika virus (ZIKV) entry, together with many other viruses, is known to be enhanced by phosphatidylserine (PS) receptors such as T-cell immunoglobulin mucin domain protein 1 (TIM-1). In this study, we demonstrate for the first time, using cell-based electrical impedance (CEI) biosensing, that ZIKV entry is also enhanced by expression of CD300a, another PS receptor. Furthermore, inhibiting CD300a in immature monocyte-derived dendritic cells partially but significantly inhibits ZIKV replication. As we have previously demonstrated that CEI is a useful tool to study Orthoflavivirus infection in real time, we now use this technology to determine how these PS receptors influence the kinetics of in vitro ZIKV infection. Results show that ZIKV entry is highly sensitive to minor changes in TIM-1 expression, both after overexpression of TIM-1 in infection-resistant HEK293T cells, as well as after partial knockout of TIM-1 in susceptible A549 cells. These results are confirmed by quantification of viral copy number and viral infectivity, demonstrating that CEI is highly suited to study and compare virus-host interactions. Overall, the results presented here demonstrate the potential of targeting this universal viral entry pathway.

GeneRaMeN enables integration, comparison, and meta-analysis of multiple ranked gene lists to identify consensus, unique, and correlated genes.

High-throughput experiments often produce ranked gene outputs, with forward genetic screening being a notable example. While there are various tools for analyzing individual datasets, those that perform comparative and meta-analytical examination of such ranked gene lists remain scarce. Here, we introduce Gene Rank Meta Analyzer (GeneRaMeN), an R Shiny tool utilizing rank statistics to facilitate the identification of consensus, unique, and correlated genes across multiple hit lists. We focused on two key topics to showcase GeneRaMeN: virus host factors and cancer dependencies. Using GeneRaMeN 'Rank Aggregation', we integrated 24 published and new flavivirus genetic screening datasets, including dengue, Japanese encephalitis, and Zika viruses. This meta-analysis yielded a consensus list of flavivirus host factors, elucidating the significant influence of cell line selection on screening outcomes. Similar analysis on 13 SARS-CoV-2 CRISPR screening datasets highlighted the pivotal role of meta-analysis in revealing redundant biological pathways exploited by the virus to enter human cells. Such redundancy was further underscored using GeneRaMeN's 'Rank Correlation', where a strong negative correlation was observed for host factors implicated in one entry pathway versus the alternate route. Utilizing GeneRaMeN's 'Rank Uniqueness', we analyzed human coronaviruses 229E, OC43, and SARS-CoV-2 datasets, identifying host factors uniquely associated with a defined subset of the screening datasets. Similar analyses were performed on over 1000 Cancer Dependency Map (DepMap) datasets spanning 19 human cancer types to reveal unique cancer vulnerabilities for each organ/tissue. GeneRaMeN, an efficient tool to integrate and maximize the usability of genetic screening datasets, is freely accessible via https://ysolab.shinyapps.io/GeneRaMeN.

A novel radial basis neural network for the Zika virus spreading model

The motive of current investigations is to design a novel radial basis neural network stochastic structure to present the numerical representations of the Zika virus spreading model (ZVSM). The mathematical ZVSM is categorized into humans and vectors based on the susceptible S(q), exposed E(q), infected I(q) and recovered R(q), i.e., SEIR. The stochastic performances are designed using the radial basis activation function, feed forward neural network, twenty-two numbers of neurons along with the optimization of Bayesian regularization in order to solve the ZVSM. A dataset is achieved using the explicit Runge-Kutta scheme, which is used to reduce the mean square error (MSE) based on the process of training for solving the nonlinear ZVSM. The division of the data is categorized into training, which is taken as 78 %, while 11 % for both authentication and testing. Three different cases of the nonlinear ZVSM have been taken, while the scheme’s correctness is performed through the matching of the results. Furthermore, the reliability of the scheme is observed by applying different performances of regression, MSE, error histograms and state transition.

Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua.

The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression of IFN-stimulated genes (ISGs) in spongiotrophoblasts but not in other placental cells that use alternate pathways to induce ISGs. ZIKV infection of Ifnar1-/- or Mavs-/- placentas was associated with greater infection of the adjacent immunocompetent decidua, and heterozygous Mavs+/- or Ifnar1+/- dams carrying immunodeficient fetuses sustained greater maternal viremia and tissue infection than dams carrying wild-type fetuses. Thus, MAVS-IFN signaling in the fetus restricts ZIKV infection in junctional zone trophoblasts, which modulates dissemination and outcome for both the fetus and the pregnant mother.

Cytoskeleton-associated gelsolin responds to the midgut distention process in saline meal-fed Aedes aegypti and affects arbovirus dissemination from the midgut.

The mosquito, Aedes aegypti, is the principal vector for several arboviruses. The mosquito midgut is the initial tissue that gets infected with an arbovirus acquired along with a blood meal from a vertebrate host. Blood meal ingestion leads to midgut tissue distention thereby increasing the pore size of the surrounding basal lamina. This allows newly synthesized virions to exit the midgut by traversing the distended basal lamina to infect secondary tissues of the mosquito. We conducted a quantitative label-free proteomic time course analysis with saline meal-fed Ae. aegypti females to identify host factors involved in midgut tissue distention. Around 2000 proteins were detected during each of the seven sampling time points and 164 of those were uniquely expressed. Forty-five of 97 differentially expressed proteins were upregulated during the 96-h time course and most of those were involved in cytoskeleton modulation, metabolic activity, and vesicle/vacuole formation. The F-actin-modulating Ae. aegypti (Aa)-gelsolin was selected for further functional studies. Stable knockout of Aa-gelsolin resulted in a mosquito line, which showed distorted actin filaments in midgut-associated tissues likely due to diminished F-actin processing by gelsolin. Zika virus dissemination from the midgut of these mosquitoes was diminished and delayed. The loss of Aa-gelsolin function was associated with an increased induction of apoptosis in midgut tissue indicating an involvement of Aa-gelsolin in apoptotic signaling in mosquitoes. Here, we used proteomics to discover a novel host factor, Aa-gelsolin, which affects the midgut escape barrier for arboviruses in mosquitoes and apoptotic signaling in the midgut.

Transcriptomic Signatures of Zika Virus Infection in Patients and a Cell Culture Model.

Zika virus (ZIKV), a re-emerging flavivirus, is associated with devasting developmental and neurological disease outcomes particularly in infants infected in utero. Towards understanding the molecular underpinnings of the unique ZIKV disease pathologies, numerous transcriptome-wide studies have been undertaken. Notably, these studies have overlooked the assimilation of RNA-seq analysis from ZIKV-infected patients with cell culture model systems. In this study we find that ZIKV-infection of human lung adenocarcinoma A549 cells, mirrored both the transcriptional and alternative splicing profiles from previously published RNA-seq data of peripheral blood mononuclear cells collected from pediatric patients during early acute, late acute, and convalescent phases of ZIKV infection. Our analyses show that ZIKV infection in cultured cells correlates with transcriptional changes in patients, while the overlap in alternative splicing profiles was not as extensive. Overall, our data indicate that cell culture model systems support dissection of select molecular changes detected in patients and establishes the groundwork for future studies elucidating the biological implications of alternative splicing during ZIKV infection.

C-FLIP facilitates ZIKV infection by mediating caspase-8/3-dependent apoptosis.

c-FLIP functions as a dual regulator of apoptosis and inflammation, yet its implications in Zika virus (ZIKV) infection remain partially understood, especially in the context of ZIKV-induced congenital Zika syndrome (CZS) where both apoptosis and inflammation play pivotal roles. Our findings demonstrate that c-FLIP promotes ZIKV infection in placental cells and myeloid-derived macrophages, involving inflammation and caspase-8/3-mediated apoptosis. Moreover, our observations reveal that c-FLIP augments ZIKV infection in multiple tissues, including blood cell, spleen, uterus, testis, and the brain of mice. Notably, the partial deficiency of c-FLIP provides protection to embryos against ZIKV-induced CZS, accompanied by a reduction in caspase-3-mediated apoptosis. Additionally, we have found a distinctive parental effect of c-FLIP influencing ZIKV replication in fetal heads. In summary, our study reveals the critical role of c-FLIP as a positive regulator in caspase-8/3-mediated apoptosis during ZIKV infection, significantly contributing to the development of CZS.

Immunological and Safety Considerations When Selecting the Dose Formulation of a Purified Inactivated Zika Virus Vaccine (PIZV).

We previously reported the first-in-human assessment of three doses (2, 5, and 10 µg) of purified inactivated Zika virus vaccine (PIZV or TAK-426) in the Phase 1 ZIK-101 study (NCT03343626). Here, we report dose selection based on extended safety and immunogenicity data (6 months post-vaccination) and discuss considerations (e.g., immunological, historic, flavivirus immunological cross-reactions) for selecting a Zika virus (ZIKV) vaccine dose formulation. TAK-426 dose selection was conducted at the first interim analysis, and was based on cumulative safety data from both flavivirus-naïve (up to ≥28 days post-dose PD2) and flavivirus-primed participants (up to ≥28 days PD1), and on immunogenicity data from flavivirus-naïve participants only (at 28 days PD1 and 28 days PD2). The safety profile from TAK-426 recipients was compared to placebo recipients. Immunogenicity was assessed by geometric mean titer ratios of neutralizing anti-ZIKV antibodies and differences in seroconversion rates. There was no significant difference in safety between the three TAK-426 doses. The 10 μg dose provided the earliest and strongest immune response (with close to 100% seroconversion and higher antibody titers PD1 in flavivirus-naïve participants), and was well tolerated with acceptable safety profiles in both flavivirus-naïve and flavivirus-primed participants; this dose was selected for further development.

Underdiagnosis of arbovirus infections in returned travelers in an area with growing circulation of Aedes albopictus in North-Eastern France

BackgroundVector-borne diseases such as malaria and arboviruses are common etiologies of post-travel fever. MethodsAfter excluding malaria, we retrospectively analyzed the diagnosis of dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) infections following recent travel by patients treated at the Strasbourg University Hospital between 2014 and 2023. Available serums (n = 35) sampled in 2023 were retrospectively tested for DENV, CHIKV, and ZIKV infections. ResultsOur results showed that 78% of the 915 malaria-negative patients without changes over the course of ten years had not undergone arbovirus infection testing. Retrospective testing revealed missing arbovirus infections: two DENV infections and one CHIKV infection, representing 8.6% (3/35) of patients for whom no mandatory declaration or vector control could be undertaken. ConclusionOur results highlight the need for early case detection, particularly in the context of the upcoming 2024 Olympic Games.