Transcriptional response of Wolbachia-transinfected Aedes aegypti mosquito cells to dengue virus at early stages of infection

2022 ◽  
Vol 103 (1) ◽  
Author(s):  
Michael Leitner ◽  
Kayvan Etebari ◽  
Sassan Asgari
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Viral Infections ◽  
Transcriptional Response ◽  
Denv Infection ◽  
Content Type ◽  
Public Health Burden ◽  
Immune Genes ◽  
Link Type ◽  
Early Stages

Mosquito-borne flaviviruses are responsible for viral infections and represent a considerable public health burden. Aedes aegypti is the principal vector of dengue virus (DENV), therefore understanding the intrinsic virus–host interactions is vital, particularly in the presence of the endosymbiont Wolbachia, which blocks virus replication in mosquitoes. Here, we examined the transcriptional response of Wolbachia -transinfected Ae. aegypti Aag2 cells to DENV infection. We identified differentially expressed immune genes that play a key role in the activation of anti-viral defence such as the Toll and immune deficiency pathways. Further, genes encoding cytosine and N6-adenosine methyltransferases and SUMOylation, involved in post-transcriptional modifications, an antioxidant enzyme, and heat-shock response were up-regulated at the early stages of DENV infection and are reported here for the first time. Additionally, several long non-coding RNAs were among the differentially regulated genes. Our results provide insight into Wolbachia -transinfected Ae. aegypti’s initial virus recognition and transcriptional response to DENV infection.

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

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
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.

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.

scholarly journals EspM Is a Conserved Transcription Factor That Regulates Gene Expression in Response to the ESX-1 System

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin G. Sanchez ◽  
Micah J. Ferrell ◽  
Alexandra E. Chirakos ◽  
Kathleen R. Nicholson ◽  
Robert B. Abramovitch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Protein Transport ◽  
Transcriptional Response ◽  
Secretion System ◽  
Pathogenic Species ◽  
Macrophage Infection ◽  
Content Type ◽  
Link Type ◽  
Phagosomal Membrane

ABSTRACT Pathogenic mycobacteria encounter multiple environments during macrophage infection. Temporally, the bacteria are engulfed into the phagosome, lyse the phagosomal membrane, and interact with the cytosol before spreading to another cell. Virulence factors secreted by the mycobacterial ESX-1 (ESAT-6-system-1) secretion system mediate the essential transition from the phagosome to the cytosol. It was recently discovered that the ESX-1 system also regulates mycobacterial gene expression in Mycobacterium marinum (R. E. Bosserman, T. T. Nguyen, K. G. Sanchez, A. E. Chirakos, et al., Proc Natl Acad Sci U S A 114:E10772–E10781, 2017, https://doi.org/10.1073/pnas.1710167114), a nontuberculous mycobacterial pathogen, and in the human-pathogenic species M. tuberculosis (A. M. Abdallah, E. M. Weerdenburg, Q. Guan, R. Ummels, et al., PLoS One 14:e0211003, 2019, https://doi.org/10.1371/journal.pone.0211003). It is not known how the ESX-1 system regulates gene expression. Here, we identify the first transcription factor required for the ESX-1-dependent transcriptional response in pathogenic mycobacteria. We demonstrate that the gene divergently transcribed from the whiB6 gene and adjacent to the ESX-1 locus in mycobacterial pathogens encodes a conserved transcription factor (MMAR_5438, Rv3863, now espM). We prove that EspM from both M. marinum and M. tuberculosis directly and specifically binds the whiB6-espM intergenic region. We show that EspM is required for ESX-1-dependent repression of whiB6 expression and for the regulation of ESX-1-associated gene expression. Finally, we demonstrate that EspM functions to fine-tune ESX-1 activity in M. marinum. Taking the data together, this report extends the esx-1 locus, defines a conserved regulator of the ESX-1 virulence pathway, and begins to elucidate how the ESX-1 system regulates gene expression. IMPORTANCE Mycobacterial pathogens use the ESX-1 system to transport protein substrates that mediate essential interactions with the host during infection. We previously demonstrated that in addition to transporting proteins, the ESX-1 secretion system regulates gene expression. Here, we identify a conserved transcription factor that regulates gene expression in response to the ESX-1 system. We demonstrate that this transcription factor is functionally conserved in M. marinum, a pathogen of ectothermic animals; M. tuberculosis, the human-pathogenic species that causes tuberculosis; and M. smegmatis, a nonpathogenic mycobacterial species. These findings provide the first mechanistic insight into how the ESX-1 system elicits a transcriptional response, a function of this protein transport system that was previously unknown.

scholarly journals Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes

2017 ◽  
Vol 115 (2) ◽  
pp. 361-366 ◽  
Author(s):  
Lauren B. Carrington ◽  
Bich Chau Nguyen Tran ◽  
Nhat Thanh Hoang Le ◽  
Tai Thi Hue Luong ◽  
Truong Thanh Nguyen ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Virus Transmission ◽  
Field Testing ◽  
Denv Infection ◽  
Ho Chi Minh City ◽  
Wild Type ◽  
Transmission Potential ◽  
Blood Meals ◽  
Increased Susceptibility

The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.

scholarly journals Cell-Fusing Agent Virus Reduces Arbovirus Dissemination in Aedes aegypti Mosquitoes In Vivo

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Artem Baidaliuk ◽  
Elliott F. Miot ◽  
Sebastian Lequime ◽  
Isabelle Moltini-Conclois ◽  
Fanny Delaigue ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Cell Line ◽  
Content Type ◽  
Cells In Culture ◽  
Mosquito Cells ◽  
Wide Range ◽  
Natural Hosts

ABSTRACT Aedes aegypti mosquitoes are the main vectors of arthropod-borne viruses (arboviruses) of public health significance, such as the flaviviruses dengue virus (DENV) and Zika virus (ZIKV). Mosquitoes are also the natural hosts of a wide range of viruses that are insect specific, raising the question of their influence on arbovirus transmission in nature. Cell-fusing agent virus (CFAV) was the first described insect-specific flavivirus, initially discovered in an A. aegypti cell line and subsequently detected in natural A. aegypti populations. It was recently shown that DENV and the CFAV strain isolated from the A. aegypti cell line have mutually beneficial interactions in mosquito cells in culture. However, whether natural strains of CFAV and DENV interact in live mosquitoes is unknown. Using a wild-type CFAV isolate recently derived from Thai A. aegypti mosquitoes, we found that CFAV negatively interferes with both DENV type 1 and ZIKV in vitro and in vivo. For both arboviruses, prior infection by CFAV reduced the dissemination titer in mosquito head tissues. Our results indicate that the interactions observed between arboviruses and the CFAV strain derived from the cell line might not be a relevant model of the viral interference that we observed in vivo. Overall, our study supports the hypothesis that insect-specific flaviviruses may contribute to reduce the transmission of human-pathogenic flaviviruses. IMPORTANCE The mosquito Aedes aegypti carries several arthropod-borne viruses (arboviruses) that are pathogenic to humans, including dengue and Zika viruses. Interestingly, A. aegypti is also naturally infected with insect-only viruses, such as cell-fusing agent virus. Although interactions between cell-fusing agent virus and dengue virus have been documented in mosquito cells in culture, whether wild strains of cell-fusing agent virus interfere with arbovirus transmission by live mosquitoes was unknown. We used an experimental approach to demonstrate that cell-fusing agent virus infection reduces the propagation of dengue and Zika viruses in A. aegypti mosquitoes. These results support the idea that insect-only viruses in nature can modulate the ability of mosquitoes to carry arboviruses of medical significance and that they could possibly be manipulated to reduce arbovirus transmission.

scholarly journals Differential replication of dengue virus serotypes 2 and 3 in coinfections of C6/36 cells and Aedes aegypti mosquitoes

2014 ◽  
Vol 8 (07) ◽  
pp. 876-884 ◽  
Author(s):  
Diana Carolina Quintero-Gil ◽  
Marta Ospina ◽  
Jorge Emilio Osorio-Benitez ◽  
Marlen Martinez-Gutierrez
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Cell Viability ◽  
Denv Infection ◽  
Replication Capacity ◽  
Denv Serotypes ◽  
Viral Genomes ◽  
Diphenyltetrazolium Bromide

Introduction: Different dengue virus (DENV) serotypes have been associated with greater epidemic potential. In turn, the increased frequency in cases of severe forms of dengue has been associated with the cocirculation of several serotypes. Because Colombia is a country with an endemic presence of all four DENV serotypes, the aim of this study was to evaluate the in vivo and in vitro replication of the DENV-2 and DENV-3 strains under individual infection and coinfection conditions. Methodology: C6/36HT cells were infected with the two strains individually or simultaneously (coinfection). Replication capacity was evaluated by RT-qPCR, and the effects on cell viability were assessed with an MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Additionally, Aedes aegypti mosquitoes were artificially fed the two strains of each serotype individually or simultaneously. The viral genomes were quantified by RT-qPCR and the survival of the infected mosquitoes was compared to that of uninfected controls. Results: In single infections, three strains significantly affected C6/36HT cell viability, but no significant differences were found in the replication capacities of the strains of the same serotype. In the in vivo infections, mosquito survival was not affected, and no significant differences in replication between strains of the same serotype were found. Finally, in coinfections, serotype 2 replicated with a thousandfold greater efficiency than serotype 3 did both in vitro and in vivo. Conclusions: Due to the cocirculation of serotypes in endemic regions, further studies of coinfections in a natural environment would further an understanding of the transmission dynamics that affect DENV infection epidemiology.

scholarly journals Dengue NS1 antigen kit shows high sensitivity for detection of recombinant dengue virus-2 NS1 antigen spiked with Aedes aegypti mosquitoes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip Raj Abraham ◽  
Bharathy R ◽  
Pradeep Kumar N ◽  
Ashwani Kumar
Keyword(s):  
Public Health ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Infected Patient ◽  
Specific Treatment ◽  
High Sensitivity ◽  
Field Evaluation ◽  
Denv Infection ◽  
Ns1 Protein ◽  
Ns1 Antigen

AbstractDengue, caused by the dengue virus (DENV) is a significant vector-borne disease. In absence of a specific treatment and vaccine, dengue is becoming a rising threat to public health. Currently, control of dengue mainly focuses on the surveillance of the mosquito vectors. Improved surveillance methods for DENV in mosquito populations would be highly beneficial to the public health. However, current methods of DENV detection in mosquitoes requires specialized equipment and expensive reagents and highly trained personnel. As an alternative, commercially available dengue NS1 antigen ELISA kits could be used for detection of DENV infection in Aedes aegypti mosquitoes. In this study, we explored the utility of commercially available Dengue NS1 antigen kit (J. Mitra & Co. Pvt. Ltd) for the detection of recombinant dengue virus-2 (rDENV-2) NS1 protein and serum of dengue infected patient spiked with Ae. aegypti mosquito pools. The kit was found to be highly sensitive and specific towards detection of all serotypes of DENV. Further, it could detect as low as 750 femto gram rDENV-2 NS1 protein. It was also observed that rDENV-2 NS1 antigen spiked with blood-fed and unfed mosquito pools could be detected. In addition, the kit also detected dengue infected patient serum spiked with Ae. aegypti mosquito pools. Overall, the Dengue NS1 antigen kit displayed high sensitivity towards detection of recombinant as well as serum NS1 protein spiked with Ae. aegypti mosquito pools and could be considered for the dengue virus surveillance after a field evaluation in Ae. aegypti mosquitoes.

scholarly journals Regulation of midgut cell proliferation impacts Aedes aegypti susceptibility to dengue virus

2018 ◽  
Author(s):  
Mabel L. Taracena ◽  
Vanessa Bottino-Rojas ◽  
Octavio A.C. Talyuli ◽  
Ana Beatriz Walter-Nuno ◽  
José Henrique M. Oliveira ◽  
...  
Keyword(s):  
Virus Infection ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Denv Infection ◽  
Pathogen Transmission ◽  
Intestinal Lumen ◽  
Midgut Cell ◽  
Vector Borne Diseases ◽  
Cellular Processes ◽  
Vector Borne

AbstractAedes aegypti is the vector of some of the most important vector-borne diseases like Dengue, Chikungunya, Zika and Yellow fever, affecting millions of people worldwide. The cellular processes that follow a blood meal in the mosquito midgut are directly associated with pathogen transmission. We studied the homeostatic response of the midgut against oxidative stress, as well as bacterial and dengue virus (DENV) infections, focusing on the proliferative ability of the intestinal stem cells (ISC). Inhibition of the peritrophic matrix (PM) formation led to an increase in ROS production by the epithelial cells in response to contact with the resident microbiota, suggesting that maintenance of low levels of ROS in the intestinal lumen is key to keep ISCs division in balance. We show that dengue virus infection induces midgut cell division in both DENV susceptible (Rockefeller) and refractory (Orlando) mosquito strains. However, the susceptible strain delays the activation of the regeneration process compared with the refractory strain. Impairment of the Delta/Notch signaling, by silencing the Notch ligand Delta using RNAi, significantly increased the susceptibility of the refractory strains to DENV infection of the midgut. We propose that this cell replenishment is essential to control viral infection in the mosquito. Our study demonstrates that the intestinal epithelium of the blood fed mosquito is able to respond and defend against different challenges, including virus infection. In addition, we provide unprecedented evidence that the activation of a cellular regenerative program in the midgut is important for the determination of the mosquito vectorial competence.

scholarly journals Discerning the role of a functional arsenic-resistance cassette in the evolution and adaptation of a rice pathogen

2021 ◽  
Vol 7 (7) ◽  
Author(s):  
Amandeep Kaur ◽  
Rekha Rana ◽  
Tanu Saroha ◽  
Prabhu B. Patil
Keyword(s):  
Type Species ◽  
Evolutionary Dynamics ◽  
Iron Acquisition ◽  
Arsenic Exposure ◽  
Resistance Mechanism ◽  
Transcriptional Response ◽  
Adaptation Mechanism ◽  
Arsenic Resistance ◽  
Content Type ◽  
Link Type

Arsenic is highly toxic element to all forms of life and is a major environmental contaminant. Understanding acquisition, detoxification and adaptation mechanisms in bacteria that are associated with the host in arsenic-rich conditions can provide novel insights into the evolutionary dynamics of host–microbe–environment interactions. In the present study, we have investigated an arsenic-resistance mechanism acquired during the evolution of a particular lineage in the population of Xanthomonas oryzae pv. oryzae, which is a serious plant pathogen infecting rice. Our study revealed the horizontal acquisition of a novel chromosomal 12 kb ars cassette in X. oryzae pv. oryzae IXO1088 that confers high resistance to arsenate/arsenite. The ars cassette comprises several genes that constitute an operon induced in the presence of arsenate/arsenite. Transfer of the cloned ars cassette to X. oryzae pv. oryzae BXO512, which lacks the cassette, confers an arsenic-resistance phenotype. Furthermore, the transcriptional response of X. oryzae pv. oryzae IXO1088 under arsenate/arsenite exposure was analysed using RNA sequencing. Arsenic detoxification and efflux, oxidative stress, iron acquisition/storage, and damage repair are the main cellular responses to arsenic exposure. Our investigation has provided insights into the existence of a novel detoxification and adaptation mechanism within the X. oryzae pv. oryzae population to deal with high-arsenic conditions outside the rice plant.

scholarly journals The transcriptional response of Aedes aegypti with variable extrinsic incubation periods for dengue virus

2018 ◽  
Author(s):  
Cassandra Koh ◽  
Scott L Allen ◽  
Rosemarie I Herbert ◽  
Elizabeth A McGraw ◽  
Stephen F Chenoweth
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Transcriptional Response ◽  
Incubation Periods
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