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.

scholarly journals The Lethal(2)-Essential-for-Life [L(2)EFL] Gene Family Modulates Dengue Virus Infection in Aedes aegypti

2020 ◽  
Vol 21 (20) ◽  
pp. 7520
Author(s):  
Lucky R. Runtuwene ◽  
Shuichi Kawashima ◽  
Victor D. Pijoh ◽  
Josef S. B. Tuda ◽  
Kyoko Hayashida ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Cell Line ◽  
Dengue Infection ◽  
Fruit Fly ◽  
Initiation Factor ◽  
Poly I:C ◽  
Gene Products ◽  
Vector Mosquito

Efforts to determine the mosquito genes that affect dengue virus replication have identified a number of candidates that positively or negatively modify amplification in the invertebrate host. We used deep sequencing to compare the differential transcript abundances in Aedes aegypti 14 days post dengue infection to those of uninfected A. aegypti. The gene lethal(2)-essential-for-life [l(2)efl], which encodes a member of the heat shock 20 protein (HSP20) family, was upregulated following dengue virus type 2 (DENV-2) infection in vivo. The transcripts of this gene did not exhibit differential accumulation in mosquitoes exposed to insecticides or pollutants. The induction and overexpression of l(2)efl gene products using poly(I:C) resulted in decreased DENV-2 replication in the cell line. In contrast, the RNAi-mediated suppression of l(2)efl gene products resulted in enhanced DENV-2 replication, but this enhancement occurred only if multiple l(2)efl genes were suppressed. l(2)efl homologs induce the phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the fruit fly Drosophila melanogaster, and we confirmed this finding in the cell line. However, the mechanism by which l(2)efl phosphorylates eIF2α remains unclear. We conclude that l(2)efl encodes a potential anti-dengue protein in the vector mosquito.

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

2020 ◽  
Vol 16 (7) ◽  
pp. e1008410 ◽  
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 ◽  
Wolbachia Strain ◽  
Virus Inhibition

scholarly journals Aedes aegypti Saliva Enhances Dengue Virus Infection of Human Keratinocytes by Suppressing Innate Immune Responses

2012 ◽  
Vol 132 (8) ◽  
pp. 2103-2105 ◽  
Author(s):  
Pornapat Surasombatpattana ◽  
Sirilaksana Patramool ◽  
Natthanej Luplertlop ◽  
Hans Yssel ◽  
Dorothée Missé
Keyword(s):  
Virus Infection ◽  
Aedes Aegypti ◽  
Immune Responses ◽  
Dengue Virus ◽  
Human Keratinocytes ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Dengue Virus Infection

scholarly journals Dengue Virus Infection of Aedes aegypti Alters Extracellular Vesicle Protein Cargo to Enhance Virus Transmission

2020 ◽  
Vol 21 (18) ◽  
pp. 6609
Author(s):  
Alexander S. Gold ◽  
Fabiana Feitosa-Suntheimer ◽  
Ricardo V. Araujo ◽  
Ryan M. Hekman ◽  
Sultan Asad ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Extracellular Vesicles ◽  
High Performance ◽  
Dengue Infection ◽  
Virus Transmission ◽  
Viral Disease ◽  
Extracellular Vesicle ◽  
Transmission Cycle ◽  
Packaging Strategy

Dengue is the most burdensome vector-borne viral disease in the world. Dengue virus (DENV), the etiological cause of dengue, is transmitted primarily by the Aedes aegypti mosquito. Like any arbovirus, the transmission cycle of dengue involves the complex interactions of a multitude of human and mosquito factors. One point during this transmission cycle that is rich in these interactions is the biting event by the mosquito, upon which its saliva is injected into the host. A number of components in mosquito saliva have been shown to play a pivotal role in the transmission of dengue, however one such component that is not as well characterized is extracellular vesicles. Here, using high-performance liquid chromatography in tandem with mass spectrometry, we show that dengue infection altered the protein cargo of Aedes aegypti extracellular vesicles, resulting in the packaging of proteins with infection-enhancing ability. Our results support the presence of an infection-dependent pro-viral protein packaging strategy that uses the differential packaging of pro-viral proteins in extracellular vesicles of Ae. aegypti saliva to promote transmission. These studies represent the first investigation into the function of Ae. aegypti extracellular vesicle cargo during dengue infection.

scholarly journals Resistance Status of Aedes albopictus (Skuse) on Malathion in Bengkulu City

2018 ◽  
Vol 7 (2) ◽  
pp. 113-119
Author(s):  
Dessy Triana ◽  
Sitti Rahmah Umniyati ◽  
Budi Mulyaningsih
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Aedes Albopictus ◽  
Adult Female ◽  
Dengue Hemorrhagic Fever ◽  
Endemic Area ◽  
Hemorrhagic Fever ◽  
Evaluation Report ◽  
Control Programs ◽  
Diagnostic Dose

Abstract Dengue Hemorrhagic Fever (DHF) is a disease caused by dengue virus and transmitted by Aedes aegypti mosquito as the main vector and Aedes albopictus as secondary vector. In 2016, Bengkulu City was one of 3 cities that experiencing DHF outbreaks in Indonesia. Insecticides malathion have been used since 1990 in bulk in DHF control programs in Bengkulu City and have not had an evaluation report on Aedes sp. vulnerability to malathion. The purpose of this research was to know the resistance status of Ae albopictus mosquitoes from endemic and sporadic areas of DHF in Bengkulu City to malathion. The sample of the study was the Ae. albopictus adult female mosquitoes which collected from endemic and sporadic areas of DHF in Bengkulu City with ovitrap installation. The resistance test was performed by CDC Bottle Bioassay method with malation 96% and 50 μg/ml diagnostic dose of. The results of this study showed 1% mortality on endemic area and 5% on sporadic area. Aedes albopictus of both areas were resistant to malathion.   Keywords: Ae. albopictus, bottle bioassay, malathion.   Abstrak Demam Berdarah Dengue (DBD) merupakan penyakit yang disebabkan oleh virus dengue dan ditularkan oleh nyamuk Aedes aegypti sebagai vektor utama dan Aedes albopictus sebagai vektor sekunder. Pada tahun 2016, Kota Bengkulu merupakan 1 dari 3 kota yang mengalami KLB DBD di Indonesia. Insektisida malation telah digunakan sejak tahun 1990 secara massal dalam program pengendalian DBD di Kota Bengkulu dan belum memiliki laporan evaluasi mengenai kerentanan Aedes sp terhadap malation. Tujuan penelitian untuk mengetahui status kerentanan nyamuk Ae. albopictus dari daerah endemis dan sporadis DBD Kota Bengkulu terhadap malation. Sampel penelitian adalah nyamuk betina dewasa Ae. albopictus yang dikoleksi dari daerah endemik dan sporadis DBD Kota Bengkulu dengan pemasangan ovitrap. Uji kerentanan dilakukan dengan metode CDC Bottle Bioassay dengan malation 96% dan dosis diagnostik 50 µg/ml. Hasil penelitian ini  menunjukkan mortalitas 1% untuk daerah endemis dan 5% untuk daerah sporadis. Aedes albopictus kedua daerah telah resisten terhadap malation.   Kata Kunci: Ae. albopictus, bottle bioassay, malation.

Discrete biological modeling for the immune response to dengue virus

2021 ◽  
Author(s):  
Khaled A. Al-Utaibi ◽  
M. Muzamil ◽  
Ayesha Sohail ◽  
Fatima Alam ◽  
Alessandro Nutini ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Complex Dynamics ◽  
Dengue Infection ◽  
Hybrid Approach ◽  
Innate Immune ◽  
Discrete Models ◽  
Proposed Model ◽  
Analysis Of Stability ◽  
Virus Produce ◽  
Viral Reproduction

Dengue infection affects more than half of the world’s population, with 1 billion symptomatic cases identified per year and several distinct genetic serotypes: DENV 1–4. Transmitted via the mosquito bite, the dengue virus infects Langerhans cells. Monocytes, B lymphocytes, and mast cells infected with dengue virus produce various cytokines although it is not clear which ones are predominant during DHF disease. A mathematical model of the Dengue virus infection is developed according to complex dynamics determined by many factors. Starting from a state of equilibrium that we could define as “virus-free” asymptotically stable with a viral reproduction number lower than one which means a very effective action of the innate immune system: it stops the infectious process, the mathematical analysis of stability in the presence of the virus demonstrates that the proposed model is dynamically influenced. Dengue fever affects more than half of the world’s population, with 1 billion symptomatic cases and multiple genetic serotypes confirmed each year, which simulates a network of interactions between the various populations involved without considering the speeds of the processes in question which are indicated in a separate computation. In this research, a hybrid approach of petri nets is utilized to connect the discrete models of dengue.

scholarly journals Considering Genomic and Immunological Correlates of Protection for a Dengue Intervention

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 203 ◽  
Author(s):  
Joshua Blight ◽  
Eduardo Alves ◽  
Arturo Reyes-Sandoval
Keyword(s):  
T Cells ◽  
Dengue Virus ◽  
Cd8 T Cells ◽  
Detrimental Effect ◽  
Dengue Infection ◽  
Denv Infection ◽  
Historical Interpretation ◽  
Correlates Of Protection ◽  
Limited Efficacy ◽  
Haemorrhagic Disease

Over three billion are at risk of dengue infection with more than 100 million a year presenting with symptoms that can lead to deadly haemorrhagic disease. There are however no treatments available and the only licensed vaccine shows limited efficacy and is able to enhance the disease in some cases. These failures have mainly been due to the complex pathology and lack of understanding of the correlates of protection for dengue virus (DENV) infection. With increasing data suggesting both a protective and detrimental effect for antibodies and CD8 T-cells whilst having complex environmental dynamics. This review discusses the roles of genomic and immunological aspects of DENV infection, providing both a historical interpretation and fresh discussion on how this information can be used for the next generation of dengue interventions.

scholarly journals Prevalence and Distribution of Dengue Virus in Aedes aegypti in Yogyakarta City before Deployment of Wolbachia Infected Aedes aegypti

2019 ◽  
Vol 16 (10) ◽  
pp. 1742 ◽  
Author(s):  
Ayu Rahayu ◽  
Utari Saraswati ◽  
Endah Supriyati ◽  
Dian Aruni Kumalawati ◽  
Rio Hermantara ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Infection Prevalence ◽  
Rt Pcr ◽  
Wet Season ◽  
Survey Period ◽  
Transmission Period ◽  
Dengue Control ◽  
Yogyakarta City

Indonesia is one of the countries where dengue infection is prevalent. In this study we measure the prevalence and distribution of dengue virus (DENV) DENV-infected Aedes aegypti in Yogyakarta City, Indonesia, during the wet season when high dengue transmission period occurred, as baseline data before implementation of a Wolbachia-infected Aedes aegypti trial for dengue control. We applied One-Step Multiplex Real Time PCR (RT-PCR) for the type-specific-detection of dengue viruses in field-caught adult Aedes aegypti mosquitoes. In a prospective field study conducted from December 2015 to May 2016, adult female Aedes aegypti were caught from selected areas in Yogyakarta City, and then screened by using RT-PCR. During the survey period, 36 (0.12%) mosquitoes from amongst 29,252 female mosquitoes were positive for a DENV type. In total, 22.20% of dengue-positive mosquitoes were DENV-1, 25% were DENV-2, 17% were DENV-3, but none were positive for DENV-4. This study has provided dengue virus infection prevalence in field-caught Aedes aegypti and its circulating serotype in Yogyakarta City before deployment of Wolbachia-infected Aedes aegypti.

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