scholarly journals Using Wolbachia to eliminate dengue – will the virus fight back?

2021 ◽  
Author(s):  
Kathryn M. Edenborough ◽  
Heather A. Flores ◽  
Cameron P. Simmons ◽  
Johanna E. Fraser
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Rna Viruses ◽  
Field Trials ◽  
Endosymbiotic Bacterium ◽  
Resistant Virus ◽  
Genetic Constraints ◽  
Positive Sense ◽  
Selection For

Recent field trials have demonstrated that dengue incidence can be substantially reduced by introgressing strains of the endosymbiotic bacterium, Wolbachia into Aedes aegypti mosquito populations. This strategy relies on Wolbachia reducing the susceptibility of Ae. aegypti to disseminated infection by positive-sense RNA viruses like dengue. However, RNA viruses are well known to adapt to antiviral pressures. Here we review the viral infection stages where selection for Wolbachia-resistant virus variants could occur. We also consider the genetic constraints imposed on viruses that alternate between vertebrate and invertebrate hosts, and the likely selection pressures that dengue virus might adapt to in order to be effectively transmitted by Ae. aegypti that carry Wolbachia. Whilst there are hurdles to dengue viruses developing resistance to Wolbachia, we suggest that long-term surveillance for resistant viruses should be an integral component of Wolbachia-introgression biocontrol programs.

scholarly journals Aedes Anphevirus: an Insect-Specific Virus Distributed Worldwide inAedes aegyptiMosquitoes That Has Complex Interplays withWolbachiaand Dengue Virus Infection in Cells

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Rhys Parry ◽  
Sassan Asgari
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Cell Line ◽  
Cell Lines ◽  
Virus Replication ◽  
Rna Viruses ◽  
Asia Pacific ◽  
Content Type ◽  
Negative Strand ◽  
Positive Sense

ABSTRACTInsect-specific viruses (ISVs) of the yellow fever mosquitoAedes aegyptihave been demonstrated to modulate transmission of arboviruses such as dengue virus (DENV) and West Nile virus by the mosquito. The diversity and composition of the virome ofA. aegypti, however, remains poorly understood. In this study, we characterized Aedes anphevirus (AeAV), a negative-sense RNA virus from the orderMononegavirales. AeAV identified fromAedescell lines was infectious to bothA. aegyptiandAedes albopictuscells but not to three mammalian cell lines. To understand the incidence and genetic diversity of AeAV, we assembled 17 coding-complete and two partial genomes of AeAV from available transcriptome sequencing (RNA-Seq) data. AeAV appears to transmit vertically and be present in laboratory colonies, wild-caught mosquitoes, and cell lines worldwide. Phylogenetic analysis of AeAV strains indicates that as theA. aegyptimosquito has expanded into the Americas and Asia-Pacific, AeAV has evolved into monophyletic African, American, and Asia-Pacific lineages. The endosymbiotic bacteriumWolbachia pipientisrestricts positive-sense RNA viruses inA. aegypti. Reanalysis of a small RNA library ofA. aegypticells coinfected with AeAV andWolbachiaproduces an abundant RNA interference (RNAi) response consistent with persistent virus replication. We foundWolbachiaenhances replication of AeAV compared to a tetracycline-cleared cell line, and AeAV modestly reduces DENV replicationin vitro. The results from our study improve understanding of the diversity and evolution of the virome ofA. aegyptiand adds to previous evidence that showsWolbachiadoes not restrict a range of negative-strand RNA viruses.IMPORTANCEThe mosquitoAedes aegyptitransmits a number of arthropod-borne viruses (arboviruses), such as dengue virus and Zika virus. Mosquitoes also harbor insect-specific viruses that may affect replication of pathogenic arboviruses in their body. Currently, however, there are only a few insect-specific viruses described fromA. aegyptiin the literature. Here, we characterize a novel negative-strand virus, AeAV. Meta-analysis ofA. aegyptisamples showed that it is present inA. aegyptimosquitoes worldwide and is vertically transmitted.Wolbachia-transinfected mosquitoes are currently being used in biocontrol, as they effectively block transmission of several positive-sense RNA viruses in mosquitoes. Our results demonstrate thatWolbachiaenhances the replication of AeAV and modestly reduces dengue virus replication in a cell line model. This study expands our understanding of the virome inA. aegyptias well as providing insight into the complexity of theWolbachiavirus restriction phenotype.

scholarly journals Long term context dependent genetic adaptation of the viral genetic cloud

2018 ◽  
Author(s):  
Tzipi Klein ◽  
Antonio V. Bordería ◽  
Cyril Barbezange ◽  
Marco Vignuzzi ◽  
Yoram Louzoun
Keyword(s):  
High Frequency ◽  
Rare Variants ◽  
Rna Viruses ◽  
Coxsackie Virus ◽  
Adaptive Landscape ◽  
Evolution System ◽  
Mutation Pattern ◽  
Selection For ◽  
Context Dependent

ABSTRACTRNA viruses generate a cloud of genetic variants within each host. This cloud contains high frequency genotypes, and a very large number of rare variants. While the dynamics of frequent variants are affected by the fitness of each variant, the rare variants cloud is affected by more complex genetic factors, including context dependent mutations. It serves as a spearhead for the viral population’s movement within the adaptive landscape. We here use an experimental evolution system to show that the genetic cloud surrounding the Coxsackie virus master sequence slowly, but steadily, evolves over hundreds of generations. The evolution of the rare variants cloud often precedes the appearance of high frequency variants. The rare variants cloud’s evolution is driven by a combination of a context-dependent mutation pattern and selection for and against specific nucleotide compositions.This combination affects the mutated dinucleotide distribution, and eventually leads to a non-uniform dinucleotide distribution in the main viral sequence. We then tested these conclusions on other RNA viruses with similar conclusions.

scholarly journals Isolation of a new strain of the flavivirus cell fusing agent virus in a natural mosquito population from Puerto Rico

2006 ◽  
Vol 87 (4) ◽  
pp. 735-748 ◽  
Author(s):  
Shelley Cook ◽  
Shannon N. Bennett ◽  
Edward C. Holmes ◽  
Reine De Chesse ◽  
Gregory Moureau ◽  
...  
Keyword(s):  
Puerto Rico ◽  
Aedes Aegypti ◽  
Rna Viruses ◽  
Mosquito Species ◽  
Viral Strain ◽  
High Similarity ◽  
Past Infection ◽  
Positive Sense ◽  
In The Wild ◽  
Viral Screening

The genus Flavivirus contains approximately 70 single-stranded, positive-sense RNA viruses that are mosquito-borne, tick-borne or have no known vector. Two discoveries support previous suggestions of the existence of a large number of unsampled flaviviruses: (i) a new flavivirus, Kamiti River virus, was recently isolated from Kenyan mosquitoes, and (ii) sequences with high similarity to those of flaviviruses have been found integrated into the genome of Aedes mosquitoes, suggesting a past infection with a virus (or viruses) that has yet to be discovered. These sequences were related most closely to a flavivirus that infects insects alone, cell fusing agent virus (CFAV). CFAV was originally isolated in the laboratory from an Aedes aegypti cell line. To date, this virus had not been found in the wild. In the present study, over 40 isolates of a novel strain of CFAV were discovered from mature mosquitoes sampled from the wild in Puerto Rico. The viral strain was present in a range of mosquito species, including Aedes aegypti, Aedes albopictus and Culex sp., from numerous locations across the island and, importantly, in mosquitoes of both sexes, suggesting vertical transmission. Here, results from viral screening, and cell culture and molecular identification of the infected mosquitoes are presented. Experimental-infection tests were also conducted by using the original CFAV strain and a highly efficient reverse-transcription mechanism has been documented, in which initiation of copying occurs at the 3′ terminus of either the genomic RNA or the intermediate of replication, potentially elucidating the mechanism by which flaviviral sequences may have integrated into mosquito genomes.

scholarly journals The Endosymbiotic Bacterium Wolbachia Induces Resistance to Dengue Virus in Aedes aegypti

2010 ◽  
Vol 6 (4) ◽  
pp. e1000833 ◽  
Author(s):  
Guowu Bian ◽  
Yao Xu ◽  
Peng Lu ◽  
Yan Xie ◽  
Zhiyong Xi
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Endosymbiotic Bacterium

scholarly journals Novel phenotype of Wolbachia strain wPip in Aedes aegypti challenges assumptions on mechanisms of Wolbachia-mediated dengue virus inhibition

2020 ◽  
Author(s):  
Johanna E. Fraser ◽  
Tanya B. O’Donnell ◽  
Johanna M. Duyvestyn ◽  
Scott L. O’Neill ◽  
Cameron P. Simmons ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Innate Immune ◽  
Control Programs ◽  
Virus Inhibition ◽  
Limited Efficacy ◽  
Positive Sense ◽  
Pathogenic Viruses ◽  
Human Infections

AbstractThe bacterial endosymbiont Wolbachia is a biocontrol tool that inhibits the ability of the Aedes aegypti mosquito to transmit positive-sense RNA viruses such as dengue and Zika. Growing evidence indicates that when Wolbachia strains wMel or wAlbB are introduced into local mosquito populations, human dengue incidence is reduced. Despite the success of this novel intervention, we still do not fully understand how Wolbachia protects mosquitoes from viral infection. Here, we demonstrate that the Wolbachia strain wPip does not inhibit virus infection in Ae. aegypti. We have leveraged this novel finding, and a panel of Ae. aegypti lines carrying virus-inhibitory (wMel and wAlbB) and non-inhibitory (wPip) strains in a common genetic background, to rigorously test a number of hypotheses about the mechanism of Wolbachia-mediated virus inhibition. We demonstrate that, contrary to previous suggestions, there is no association between a strain’s ability to inhibit dengue infection in the mosquito and either its typical density in the midgut or salivary glands, or the degree to which it elevates innate immune response pathways in the mosquito. These findings, and the experimental platform provided by this panel of genetically comparable mosquito lines, clear the way for future investigations to define how Wolbachia prevents Ae. aegypti from transmitting viruses.Author summaryDengue virus, transmitted by the Aedes aegypti mosquito, is one of the fastest-growing infectious diseases, causing an estimated 390 million human infections per year worldwide. Vaccines have limited efficacy and there are no approved therapeutics. This has driven the rise of novel vector control programs, in particular those that use the bacterium, Wolbachia, which prevents transmission of dengue and other human pathogenic viruses when stably introduced into Ae. aegypti populations. Although this is proving to be a highly effective method, the details of how this biocontrol tool works are not well understood. Here we characterise a new Wolbachia strain, wPip, and find that Ae. aegypti carrying wPip are still able to transmit dengue similar to mosquitoes that do not carry Wolbachia. This finding has allowed us to begin a rigorous program of comparative studies to determine which features of a Wolbachia strain determine whether it is antiviral. Understanding these mechanisms will enable us to predict the risk of viral resistance arising against Wolbachia and facilitate preparation of second-generation field release lines.

scholarly journals Transcriptional Response of Wolbachia to Dengue Virus Infection in Cells of the Mosquito Aedes aegypti

mSphere ◽  
2021 ◽  
Author(s):  
Michael Leitner ◽  
Cameron Bishop ◽  
Sassan Asgari
Keyword(s):  
Virus Infection ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Transcriptional Response ◽  
Endosymbiotic Bacterium ◽  
Dengue Virus Infection ◽  
Content Type ◽  
Virus Inhibition ◽  
Pathogenic Viruses

Aedes aegypti is a vector of several pathogenic viruses, including dengue, Zika, chikungunya, and yellow fever viruses, which are of importance to human health. Wolbachia is an endosymbiotic bacterium currently used in transinfected mosquitoes to suppress replication and transmission of dengue viruses. However, the mechanism of Wolbachia -mediated virus inhibition is not fully understood.

Detection of dengue virus in Aedes mosquitoes in Delhi, India

ENTOMON ◽  
2019 ◽  
Vol 44 (3) ◽  
pp. 213-218
Author(s):  
Suresh Chand Kaushik ◽  
Sukhvir Singh ◽  
Purnima Srivastava ◽  
R. Rajendran
Keyword(s):  
Early Intervention ◽  
Early Detection ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Infection Rate ◽  
Transmission Season ◽  
Aedes Mosquitoes ◽  
Alternative Approach ◽  
Human Sera ◽  
Minimum Infection Rate

Detection of viruses in human sera particularly in endemic areas is cumbersome and laborious. Therefore, an alternative approach, Immuno-fluorescence assay (IFA) was performed to determine dengue virus (DENV) positivity in mosquitoes. A total of 1055 adult Aedes aegypti female mosquitoes were tested for IFA test against DENV. Minimum infection rate (MIR) for DENV was found higher during August to November 2016 ranging from 10.75 to 20.83. The average yearly MIR was about 6.64. Higher MIR for Ae. aegypti was found in Sarfabad, Noida (12.71) and Khoda Colony, Ghaziabad (11.90). Minimum MIR (4.67) was observed in Sanjay colony (Faridabad). The main contribution of this study resides in the development of a more suitable monitoring system for early detection of viral circulation and to prioritize early intervention in the non-transmission season.

Difusi dan Pola Spasial Sebaran Penyakit Demam Berdarah Dengue (DBD) Di Kota Bandar Lampung

2018 ◽  
Vol 1 (1) ◽  
pp. 87-95
Author(s):  
Nurul Qamila ◽  
Agel Vidian Krama
Keyword(s):  
Public Health ◽  
Spatial Analysis ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Spatial Pattern ◽  
Dengue Hemorrhagic Fever ◽  
Health Problem ◽  
Public Health Problem ◽  
Hemorrhagic Fever ◽  
Descriptive Method

Dengue hemorrhagic fever (DHF) is a contagious disease caused by the dengue virus and is transmitted by the mosquito Aedes aegypti (Aa.aegypti). The population is still a public health problem that increases the number of sufferers and also widespread, with population and education. This study aims to reveal the spatial pattern and distribution of Dengue Hemorrhagic Fever (DHF) with the spatial pattern and the spread of Dengue Hemorrhagic Fever (DHF) can result in different locations of these allegations. From the map that can be used for the prevention of Dengue Hemorrhagic Fever (DBD) in Bandar Lampung City. This study aims to reveal the spatial pattern and distribution of Dengue Hemorrhagic Fever (DHF) with the descriptive method and spatial pattern of Dengue Hemorrhagic Fever (DHF) can result in different locations of these allegations. From the map that can be used for the prevention of Dengue Hemorrhagic Fever (DBD) in Bandar Lampung City. Keywords: DHF, Spatial Analysis

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