Wolbachia
            strain
            w
            AlbA blocks Zika virus transmission in
            Aedes aegypti

In urban settings, chikungunya, Zika, and dengue viruses are transmitted by Aedes aegypti mosquitoes. Since these viruses co-circulate in several regions, coinfection in humans and vectors may occur, and human coinfections have been frequently reported. Yet, little is known about the molecular aspects of virus interactions within hosts and how they contribute to arbovirus transmission dynamics. We have previously shown that Aedes aegypti exposed to chikungunya and Zika viruses in the same blood meal can become coinfected and transmit both viruses simultaneously. However, mosquitoes may also become coinfected by multiple, sequential feeds on single infected hosts. Therefore, we tested whether sequential infection with chikungunya and Zika viruses impacts mosquito vector competence. We exposed Ae. aegypti mosquitoes first to one virus and 7 days later to the other virus and compared infection, dissemination, and transmission rates between sequentially and single infected groups. We found that coinfection rates were high after sequential exposure and that mosquitoes were able to co-transmit both viruses. Surprisingly, chikungunya virus coinfection enhanced Zika virus transmission 7 days after the second blood meal. Our data demonstrate heterologous arbovirus synergism within mosquitoes, by unknown mechanisms, leading to enhancement of transmission under certain conditions.

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Subgenomic flavivirus RNA binds the mosquito DEAD/H-box helicase ME31B and determines Zika virus transmission by Aedes aegypti

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1905617116 ◽

2019 ◽

Vol 116 (38) ◽

pp. 19136-19144 ◽

Cited By ~ 17

Author(s):

Giel P. Göertz ◽

Joyce W. M. van Bree ◽

Anwar Hiralal ◽

Bas M. Fernhout ◽

Carmen Steffens ◽

...

Keyword(s):

Aedes Aegypti ◽

Zika Virus ◽

Affinity Purification ◽

Mechanistic Model ◽

Virus Transmission ◽

Protein Translation ◽

Mass Spectrometry Analysis ◽

Small Interfering Rnas ◽

Spectrometry Analysis ◽

Mosquito Infection

Zika virus (ZIKV) is an arthropod-borne flavivirus predominantly transmitted by Aedes aegypti mosquitoes and poses a global human health threat. All flaviviruses, including those that exclusively replicate in mosquitoes, produce a highly abundant, noncoding subgenomic flavivirus RNA (sfRNA) in infected cells, which implies an important function of sfRNA during mosquito infection. Currently, the role of sfRNA in flavivirus transmission by mosquitoes is not well understood. Here, we demonstrate that an sfRNA-deficient ZIKV (ZIKVΔSF1) replicates similar to wild-type ZIKV in mosquito cell culture but is severely attenuated in transmission by Ae. aegypti after an infectious blood meal, with 5% saliva-positive mosquitoes for ZIKVΔSF1 vs. 31% for ZIKV. Furthermore, viral titers in the mosquito saliva were lower for ZIKVΔSF1 as compared to ZIKV. Comparison of mosquito infection via infectious blood meals and intrathoracic injections showed that sfRNA is important for ZIKV to overcome the mosquito midgut barrier and to promote virus accumulation in the saliva. Next-generation sequencing of infected mosquitoes showed that viral small-interfering RNAs were elevated upon ZIKVΔSF1 as compared to ZIKV infection. RNA-affinity purification followed by mass spectrometry analysis uncovered that sfRNA specifically interacts with a specific set of Ae. aegypti proteins that are normally associated with RNA turnover and protein translation. The DEAD/H-box helicase ME31B showed the highest affinity for sfRNA and displayed antiviral activity against ZIKV in Ae. aegypti cells. Based on these results, we present a mechanistic model in which sfRNA sequesters ME31B to promote flavivirus replication and virion production to facilitate transmission by mosquitoes.

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Modeling of the spatial distribution of the vector Aedes Aegypti, transmitter of the Zika Virus in continental Ecuador by the application of GIS tools

Bionatura ◽

10.21931/rb/20120.05.04.7 ◽

2020 ◽

Vol 5 (4) ◽

pp. 1314-1327

Author(s):

Mario Bolivar Balseca Carrera ◽

Oswaldo Padilla Almeida ◽

Theofilos Toulkeridis

Keyword(s):

Aedes Aegypti ◽

Zika Virus ◽

Characteristic Curve ◽

Confusion Matrix ◽

Virus Transmission ◽

Predictive Performance ◽

Actual Distribution ◽

Gis Tools ◽

Presence Data ◽

Epidemiological Risk

In recent years Ecuador has suffered from the Zika virus. Geo-software and statistical software allowed the probabilistic identification of suitable ecological niche species, such as the vector Aedes aegypti, which is the leading cause of the Zika virus transmission, depending on the dependent and independent variables. These models require pre-weighted input, normalized, and rasterized inputs to continue the validation process to estimate their predictive performance through several statistics such as the confusion matrix or the Receiver Operating Characteristic Curve (ROC). It resulted that the Maxent method has been with the higher predictive performance with a value of Area Under Curve (AUC) = 0.998, which describes the areas of Zika with a greater probability of the transmission vector resembling the actual distribution of the species as a function of the presence data and the predictor variables. A large part of the Ecuadorian coastal territory yielded a statistical-based, probabilistic presence of the vector, being the most vulnerable before a possible epidemiological risk.

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Coupled small molecules target RNA interference and JAK/STAT signaling to reduce Zika virus infection in Aedes aegypti

10.1101/2021.08.23.457417 ◽

2021 ◽

Author(s):

Chasity E. Trammell ◽

Gabriela Ramirez ◽

Irma Sanchez-Vargas ◽

Shirley Luckhart ◽

Rushika Perera ◽

...

Keyword(s):

Aedes Aegypti ◽

Small Molecules ◽

Insulin Signaling ◽

Zika Virus ◽

Disease Incidence ◽

Virus Transmission ◽

Zikv Infection ◽

Small Molecule Drugs ◽

Pathway Activation ◽

Target Rna

The recent global Zika epidemics have revealed the significant threat that mosquito-borne viruses pose. There are currently no effective vaccines or prophylactics to prevent Zika virus (ZIKV) infection. Limiting exposure to infected mosquitoes is best way to reduce disease incidence. Recent studies have focused on targeting mosquito reproduction and immune responses to reduce transmission. In particular, previous work evaluated the effect of insulin signaling on antiviral JAK/STAT and RNAi in vector mosquitoes. In this work, we demonstrate that targeting insulin signaling through the repurposing of small molecule drugs results in the activation of both of these antiviral pathways. Activation of this coordinated response additively reduced ZIKV levels in Aedes aegypti mosquitoes. This effect included a quantitatively greater reduction in salivary gland ZIKV levels relative to single pathway activation, indicating the potential for field delivery of these small molecules to substantially reduce virus transmission.

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Using Barcoded Zika Virus to Assess Virus Population Structure in vitro and in Aedes aegypti Mosquitoes

10.1101/222984 ◽

2017 ◽

Author(s):

James Weger-Lucarelli ◽

Selene M. Garcia ◽

Claudia Rückert ◽

Alex Byas ◽

Shelby L. O’Connor ◽

...

Keyword(s):

Genetic Diversity ◽

Next Generation Sequencing ◽

Aedes Aegypti ◽

Zika Virus ◽

Virus Transmission ◽

Viral Diversity ◽

Virus Population ◽

Generation Sequencing

ABSTRACTArboviruses such as Zika virus (ZIKV, Flaviviridae; Flavivirus) replicate in both mammalian and insect hosts where they encounter a variety of distinct host defenses. To overcome these pressures, arboviruses exist as diverse populations of distinct genomes. However, transmission between hosts and replication within hosts can involve genetic bottlenecks, during which population size and viral diversity may be significantly reduced, potentially resulting in large fitness losses. Understanding the points at which bottlenecks exist during arbovirus transmission is critical to identifying targets for preventing transmission. To study these bottleneck effects, we constructed 4 “barcoded” ZIKV clones - 2 with an 8-base-pair degenerate insertion in the 3’ UTR and 2 with 8 or 9 degenerate synonymous changes in the coding sequence, theoretically containing thousands of variants each. We passaged these viruses 3 times each in 2 mammalian and 2 mosquito cell lines and characterized selection of the “barcode” populations using deep sequencing. Additionally, the viruses were used to feed three recently field-caught populations of Aedes aegypti mosquitoes to assess bottlenecks in a natural host. The barcoded viruses replicated well in multiple cell lines in vitro and in vivo in mosquitoes and could be characterized using next-generation sequencing. The stochastic nature of mosquito transmission was clearly shown by tracking individual barcodes in Ae. aegypti mosquitoes. Barcoded viruses provide an efficient method to examine bottlenecks during virus infection.AUTHOR SUMMARYIn general, mosquito-borne viruses like ZIKV must replicate in two very different host environments: an insect and a mammalian host. RNA viruses such as ZIKV must maintain genetic diversity in order to adapt to these changing conditions. During this transmission cycle, several barriers exist which can severely restrict viral genetic diversity, causing bottlenecks in the virus population. It is critical to understand these bottlenecks during virus transmission as this will provide important insights into the selective forces shaping arbovirus evolution within and between hots. Here, we employ a set of barcoded ZIKV constructs containing a degenerate stretch of nucleotides that can be tracked using next-generation sequencing. We found that the insertion site in the genome was an important determinant of the resulting diversity of the genetic barcode. We also found that bottlenecks varied between different mosquito populations and patterns of genetic diversity were distinct among individual mosquitoes within a single population, highlighting the randomness of virus dissemination in mosquitoes. Our study characterizes a new tool for tracking bottlenecks during virus transmission in vivo and highlights the importance of both viral and host factors on the maintenance of viral diversity.

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The Wolbachia strain wAu provides highly efficient virus transmission blocking in Aedes aegypti

PLoS Pathogens ◽

10.1371/journal.ppat.1006815 ◽

2018 ◽

Vol 14 (1) ◽

pp. e1006815 ◽

Cited By ~ 77

Author(s):

Thomas H. Ant ◽

Christie S. Herd ◽

Vincent Geoghegan ◽

Ary A. Hoffmann ◽

Steven P. Sinkins

Keyword(s):

Aedes Aegypti ◽

Virus Transmission ◽

Wolbachia Strain ◽

Transmission Blocking ◽

Highly Efficient

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Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika Virus Infection

mSphere ◽

10.1128/msphere.00456-17 ◽

2017 ◽

Vol 2 (6) ◽

Cited By ~ 30

Author(s):

Kayvan Etebari ◽

Shivanand Hegde ◽

Miguel A. Saldaña ◽

Steven G. Widen ◽

Thomas G. Wood ◽

...

Keyword(s):

Virus Infection ◽

Aedes Aegypti ◽

Dengue Virus ◽

Zika Virus ◽

Virus Transmission ◽

Noncoding Rnas ◽

Transcriptional Response ◽

Mosquito Vector ◽

Content Type ◽

Zika Virus Infection

ABSTRACT Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection. Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti, which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.

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Vector competence of Aedes aegypti and Culex quinquefasciatus from the metropolitan area of Guadalajara, Jalisco, Mexico for Zika virus

Scientific Reports ◽

10.1038/s41598-019-53117-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Darwin Elizondo-Quiroga ◽

Miriam Ramírez-Medina ◽

Abel Gutiérrez-Ortega ◽

Armando Elizondo-Quiroga ◽

José Esteban Muñoz-Medina ◽

...

Keyword(s):

Aedes Aegypti ◽

Culex Quinquefasciatus ◽

Zika Virus ◽

Vector Competence ◽

Virus Transmission ◽

Blood Feeding ◽

Surveillance Program ◽

Virus Spread ◽

Zikv Infection ◽

Almost All

AbstractZika virus (ZIKV) is a mosquito-borne pathogen discovered in the late 40’s in Uganda during a surveillance program for yellow fever. By 2014 the virus reached Eastern Island in the Americas, and two years later, the virus spread to almost all countries and territories of the Americas. The mosquito Aedes aegypti has been identified as the main vector of the disease, and several researchers have also studied the vector competence of Culex quinquefasciatus in virus transmission. The aim of the present study was to evaluate the vector competence of Ae. aegypti and Cx. quinquefasciatus in order to understand their roles in the transmission of ZIKV in Guadalajara, Jalisco, Mexico. In blood feeding laboratry experiments, we found that Ae. aegypti mosquitoes showed to be a competent vector able to transmit ZIKV in this area. On the other hand, we found that F0 Cx. quinquefasciatus mosquitoes are refractory to ZIKV infection, dissemination and transmission.

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