Metabolic Processes Are Differentially Regulated During Wild-Type and Attenuated Dengue Virus Infection in Aedes aegypti

2022 ◽  
Author(s):  
Tanamas Siriphanitchakorn ◽  
Cassandra Modahl ◽  
R. Manjunatha Kini ◽  
Eng Eong Ooi ◽  
Milly Choy
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Denv Infection ◽  
Critical Event ◽  
Mosquito Vectors ◽  
Wild Type ◽  
Metabolic Processes ◽  
Transcriptomic Response ◽  
Host Interactions ◽  
Future Work

Successful completion of the dengue virus (DENV) life cycle in its mosquito vectors is important for efficient human–mosquito–human cycle of transmission, but the virus–mosquito interactions that underpin this critical event are poorly defined. To understand the virus–host interactions that determine viral infection by Aedes aegypti, the principal DENV vector, the authors compared transcriptomic changes in the head/thorax of the mosquito after intrathoracic infection with the wild-type DENV2 16681 strain and its attenuated derivative, PDK53. Using high-throughput RNA-sequencing, the authors identified 1,629 differentially expressed genes (DEGs) during 16681 infection, compared with only 22 DEGs identified during PDK53 infection, indicating that 16681 infection triggers a more robust host transcriptomic response compared with PDK53 infection. The authors further found that 16681 infection, but not PDK53 infection, altered metabolism in these heads/thoraces. Altogether, our findings reveal differential regulation of metabolic processes during wild-type and attenuated DENV infection, and suggest the need for future work to study the role of metabolic processes in determining DENV infection and replication in its mosquito vectors.

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 Revisiting dengue virus-mosquito interactions: molecular insights into viral fitness

2021 ◽  
Vol 102 (11) ◽  
Author(s):  
Tanamas Siriphanitchakorn ◽  
R. Manjunatha Kini ◽  
Eng Eong Ooi ◽  
Milly M. Choy
Keyword(s):  
Life Cycle ◽  
Dengue Virus ◽  
Denv Infection ◽  
Viral Fitness ◽  
Host Factors ◽  
Mammalian Host ◽  
Mosquito Vectors ◽  
Host Interactions ◽  
Cellular Processes ◽  
Natural Hosts

Dengue virus (DENV), like other viruses, closely interacts with the host cell machinery to complete its life cycle. Over the course of infection, DENV interacts with several host factors with pro-viral activities to support its infection. Meanwhile, it has to evade or counteract host factors with anti-viral activities which inhibit its infection. These molecular virus-host interactions play a crucial role in determining the success of DENV infection. Deciphering such interactions is thus paramount to understanding viral fitness in its natural hosts. While DENV-mammalian host interactions have been extensively studied, not much has been done to characterize DENV-mosquito host interactions despite its importance in controlling DENV transmission. Here, to provide a snapshot of our current understanding of DENV-mosquito interactions, we review the literature that identified host factors and cellular processes related to DENV infection in its mosquito vectors, Aedes aegypti and Aedes albopictus, with a particular focus on DENV-mosquito omics studies. This knowledge provides fundamental insights into the DENV life cycle, and could contribute to the development of novel antiviral strategies.

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 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 Sialic Acid Expression in the MosquitoAedes aegyptiand Its Possible Role in Dengue Virus-Vector Interactions

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Jorge Cime-Castillo ◽  
Philippe Delannoy ◽  
Guillermo Mendoza-Hernández ◽  
Verónica Monroy-Martínez ◽  
Anne Harduin-Lepers ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Mammalian Cells ◽  
Vector Competence ◽  
Denv Infection ◽  
Viral Disease ◽  
Salivary Gland Extract ◽  
Denv Serotypes ◽  
Mosquito Saliva

Dengue fever (DF) is the most prevalent arthropod-borne viral disease which affects humans. DF is caused by the four dengue virus (DENV) serotypes, which are transmitted to the host by the mosquitoAedes aegyptithat has key roles in DENV infection, replication, and viral transmission (vector competence). Mosquito saliva also plays an important role during DENV transmission. In this study, we detected the presence of sialic acid (Sia) inAedes aegyptitissues, which may have an important role during DENV-vector competence. We also identified genome sequences encoding enzymes involved in Sia pathways. The cDNA forAedes aegyptiCMP-Sia synthase (CSAS) was amplified, cloned, and functionally evaluated via the complementation of LEC29.Lec32 CSAS-deficient CHO cells.AedesCSAS-transfected LEC29.Lec32 cells were able to express Sia moieties on the cell surface. Sequences related toα-2,6-sialyltransferase were detected in theAedes aegyptigenome. Likewise, we identified Sia-α-2,6-DENV interactions in different mosquito tissues. In addition, we evaluated the possible role of sialylated molecules in a salivary gland extract during DENV internalization in mammalian cells. The knowledge of early DENV-host interactions could facilitate a better understanding of viral tropism and pathogenesis to allow the development of new strategies for controlling DENV transmission.

scholarly journals An Aedes aegypti-associated fungus increases susceptibility to dengue virus by modulating gut trypsin activity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yesseinia I Angleró-Rodríguez ◽  
Octavio AC Talyuli ◽  
Benjamin J Blumberg ◽  
Seokyoung Kang ◽  
Celia Demby ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Digestive Enzyme ◽  
Denv Infection ◽  
Trypsin Activity ◽  
Infection Cycle ◽  
Successful Completion ◽  
Associated Bacteria ◽  
Secreted Factors ◽  
First Time

Transmission of dengue virus (DENV) requires successful completion of the infection cycle in the Aedes aegypti vector, which is initiated in the midgut tissue after ingestion of an infectious blood meal. While certain Ae. aegypti midgut-associated bacteria influence virus infection, little is known about the midgut-associated fungi (mycobiota), and how its members might influence susceptibility to DENV infection. We show that a Talaromyces (Tsp_PR) fungus, isolated from field-caught Ae. aegypti, render the mosquito more permissive to DENV infection. This modulation is attributed to a profound down-regulation of digestive enzyme genes and trypsin activity, upon exposure to Tsp_PR-secreted factors. In conclusion, we show for the first time that a natural mosquito gut-associated fungus can alter Ae. aegypti physiology in a way that facilitates pathogen infection.

scholarly journals Individual-based dengue virus surveillance in Aedes aegypti mosquitoes collected concurrently with suspected patients in Tarlac City, Philippines

2020 ◽  
Author(s):  
Jean Claude Balingit ◽  
Thaddeus M. Carvajal ◽  
Mariko Saito-Obata ◽  
Maribet Gamboa ◽  
Amalea Dulcene Nicolasora ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Phylogenetic Analyses ◽  
Simultaneous Detection ◽  
Denv Infection ◽  
Health Concern ◽  
Effective Control ◽  
Entomological Surveillance ◽  
Mosquito Abundance ◽  
Virus Surveillance

Abstract Background Dengue virus (DENV) infection continues to be a major public health concern throughout tropical and subtropical regions of the world where Aedes aegypti mosquitoes, its primary vector, dwell. In the context of DENV transmission, effective control is reliant not only on knowledge of mosquito abundance, but also on mosquito infection. In the 2015 dengue season, we conducted a one-month entomological surveillance of adult Aedes aegypti mosquitoes around households of suspected dengue patients in Tarlac City, Philippines to assess the DENV infection rate in the local mosquito population, and to identify the DENV genotypes and serotypes concurrently co-circulating in mosquitoes and patients. Methods We performed a one-step multiplex real-time RT-PCR assay for the simultaneous detection and serotyping of DENV in patients and in individual female Aedes aegypti mosquito. Consequently, we performed sequencing and phylogenetic analyses to further characterize the detected DENVs in mosquitoes and patients at the genotype level. Results We collected a total of 583 adult Aedes aegypti mosquitoes, of which we tested 359 female mosquitoes individually for the presence of the DENV. Ten mosquitoes (2.8%) from amongst 359 female mosquitoes were confirmed to be positive for the presence of the DENV. We detected DENV-1, DENV-2, and DENV-4 in the field-collected mosquitoes, which were consistent with the serotypes concurrently infecting patients. Sequencing and phylogenetic analyses of the detected DENVs based on the partial envelope ( E ) gene revealed three genotypes concurrently present in the sampled mosquitoes and patients during the study period, namely: DENV-1 genotype IV, DENV-2 Cosmopolitan genotype and DENV-4 genotype II. Notably, we observed a random geographic distribution of DENVs in the study area suggesting the occurrence of active DENV transmission within and outside the vicinities of Tarlac City. Conclusions In this study, we demonstrate the utility of an individual-based DENV surveillance in field-collected mosquitoes and the importance of incorporating mosquito virus data in phylogenetic studies. Analyzing virus sequences from vector and host could potentially improve our understanding of the dynamics of DENV transmission.

scholarly journals Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination

2020 ◽  
Author(s):  
Alejandro Marin-Lopez ◽  
Junjun Jiang ◽  
Yuchen Wang ◽  
Yongguo Cao ◽  
Tyler MacNeil ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Denv Infection ◽  
Infected Mosquito ◽  
Viral Dissemination ◽  
Protein Components ◽  
Calcium Transporter

AbstractDengue virus (DENV) is a flavivirus that causes marked human morbidity and mortality worldwide, being transmitted to humans by Aedes aegypti mosquitoes. Habitat expansion of Aedes, mainly due to climate change and increasing overlap between urban and wild habitats, places nearly half of the world’s population at risk for DENV infection. After a bloodmeal from a DENV-infected host, the virus enters the mosquito midgut. Next, the virus migrates to, and replicates in, other tissues, like salivary glands. Successful viral transmission occurs when the infected mosquito takes another blood meal on a susceptible host and DENV is released from the salivary gland via saliva into the skin. During viral dissemination in the mosquito and transmission to a new mammalian host, DENV interacts with a variety of vector proteins, which are uniquely important during each phase of the viral cycle. Our study focuses on the interaction between DENV particles and protein components in the A. aegypti vector. We performed a mass spectrometry assay where we identified a set of A aegypti salivary gland proteins which potentially interact with the DENV virion. Using dsRNA to silence gene expression, we analyzed the role of these proteins in viral infectivity. Two of these candidates, a synaptosomal-associated protein (AeSNAP) and a calcium transporter ATPase (ATPase) appear to play a role in viral replication both in vitro and in vivo. These findings suggest that AeSNAP plays a protective role during DENV infection of mosquitoes and that ATPase protein is required for DENV during amplification within the vector.ImportanceAedes aegypti mosquitoes are the major vector of different flaviviruses that cause human diseases, including dengue virus. There is a great need for better therapeutics and preventive vaccines against flaviviruses. Flaviviruses create complex virus-host and virus-vector interactions. The interactions between viral particles and protein components in the vector is not completely understood. In this work we characterize how two mosquito proteins, “AeSNAP” and “ATPase”, influence DENV viral dissemination within A. aegypti, using both in vitro and in vivo models. These results elucidate anti-vector measures that may be potentially be used to control dengue virus spread in the mosquito vector.

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