scholarly journals Identification of dengue virus immunodeficiency (IMD) pathway antagonists in Aedes Aegypti cells

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Tiffany Russell ◽  
Louisa Wallace ◽  
Kevin Maringer
Keyword(s):  
Aedes Aegypti ◽  
Immune Responses ◽  
Dengue Virus ◽  
Mosquito Vector ◽  
Dengue Disease ◽  
Host Interactions ◽  
Host Determinants ◽  
Imd Pathway ◽  
Insight Into ◽  
Potential Antagonist

The flavivirus dengue virus (DENV) is the most significant arthropod borne virus (arbovirus) of humans, causing serious morbidity and mortality, with nearly half of the world’s population at risk of infection. Due to a lack of antivirals and limited vaccine options, vector control remains a vital defence against dengue disease. The mosquito Aedes aegypti is the major vector for DENV, and understanding mosquito immune responses and how DENV may evade them is critical. We have shown that DENV-2 can inhibit the exogenous induction of immune deficiency (IMD) signalling by classical immune stimuli. Therefore, we aimed to identify DENV antagonists of the IMD pathway, and define the molecular virus and host determinants of IMD antagonism in a well characterised Ae. aegypti derived cell line, Aag2. Each DENV protein was expressed individually in Aag2 cells and tested for their ability to block IMD signalling induced by exogenous stimuli. This screen identified NS4A as a potential antagonist of the IMD pathway. Further, we have found that the N-terminus of NS4A is responsible for this inhibition. The antagonism of IMD signalling is specific to flaviviruses transmitted by a mosquito vector, illustrating the importance of both the IMD pathway for mosquito immunity and the antagonism of this pathway by DENV. By enhancing our understanding of how DENV evades the mosquito immune response at a molecular level, we will gain insight into virus-host interactions constraining arbovirus transmission and emergence, which may be exploited for developing transmission-incompetent vectors to reduce the burden of dengue disease.

scholarly journals Aedes aegypti (Diptera: Culicidae) Immune Responses with Different Feeding Regimes Following Infection by the Entomopathogenic Fungus Metarhizium anisopliae

Insects ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 95 ◽  
Author(s):  
Sara Cabral ◽  
Adriano de Paula ◽  
Richard Samuels ◽  
Rodrigo da Fonseca ◽  
Simone Gomes ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Immune Responses ◽  
Antimicrobial Peptides ◽  
Fungal Infection ◽  
Fat Body ◽  
Negative Regulator ◽  
Toll Pathway ◽  
Promising Alternative ◽  
Imd Pathway ◽  
Feeding Regimes

The mosquito Aedes aegypti is the most notorious vector of illness-causing viruses. The use of entomopathogenic fungi as bioinsecticides is a promising alternative for the development of novel mosquito control strategies. We investigate whether differences in immune responses could be responsible for modifications in survival rates of insects following different feeding regimes. Sucrose and blood-fed adult A. aegypti females were sprayed with M. anisopliae 1 × 106 conidia mL−1, and after 48 h, the midgut and fat body were dissected. We used RT-qPCR to monitor the expression of Cactus and REL1 (Toll pathway), IMD, REL2, and Caspar (IMD pathway), STAT and PIAS (JAK-STAT pathway), as well as the expression of antimicrobial peptides (Defensin A, Attacin and Cecropin G). REL1 and REL2 expression in both the midgut and fat body were higher in blood-fed fungus-challenged A. aegypti than in sucrose-fed counterparts. Interestingly, infection of sucrose-fed insects induced Cactus expression in the fat body, a negative regulator of the Toll pathway. The IMD gene was upregulated in the fat body in response to fungal infection after a blood meal. Additionally, we observed the induction of antimicrobial peptides in the blood-fed fungus-challenged insects. This study suggests that blood-fed A. aegypti are less susceptible to fungal infection due to the rapid induction of Toll and IMD immune pathways.

Aedes aegypti Immune Responses to Dengue Virus

2016 ◽  
pp. 129-143 ◽  
Author(s):  
Cole Schonhofer ◽  
Heather Coatsworth ◽  
Paola Caicedo ◽  
Clara Ocampo ◽  
Carl Lowenberger
Keyword(s):  
Aedes Aegypti ◽  
Immune Responses ◽  
Dengue Virus

scholarly journals Route of inoculation and mosquito vector exposure modulate dengue virus replication kinetics and immune responses in rhesus macaques

2020 ◽  
Vol 14 (4) ◽  
pp. e0008191
Author(s):  
Michael K. McCracken ◽  
Gregory D. Gromowski ◽  
Lindsey S. Garver ◽  
Brad A. Goupil ◽  
Kathryne D. Walker ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Virus Replication ◽  
Rhesus Macaques ◽  
Mosquito Vector

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 Correlating Remote Sensing Data with the Abundance of Pupae of the Dengue Virus Mosquito Vector, Aedes aegypti, in Central Mexico

2014 ◽  
Vol 3 (2) ◽  
pp. 732-749 ◽  
Author(s):  
Max Moreno-Madriñán ◽  
William Crosson ◽  
Lars Eisen ◽  
Sue Estes ◽  
Maurice Estes Jr. ◽  
...  
Keyword(s):  
Remote Sensing ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Remote Sensing Data ◽  
Central Mexico ◽  
Mosquito Vector ◽  
Sensing Data

scholarly journals Imd pathway-specific immune assays reveal NF-κB stimulation by viral RNA PAMPs in Aedes aegypti Aag2 cells

2020 ◽  
Author(s):  
Tiffany A. Russell ◽  
Andalus Ayaz ◽  
Andrew D. Davidson ◽  
Ana Fernandez-Sesma ◽  
Kevin Maringer
Keyword(s):  
Immune System ◽  
Aedes Aegypti ◽  
Immune Responses ◽  
Health Impact ◽  
Global Public Health ◽  
Toll Pathway ◽  
Experimental Conditions ◽  
Imd Pathway ◽  
Arboviral Diseases ◽  
Transgenic Insects

ABSTRACTBackgroundThe mosquito Aedes aegypti is a major vector for the arthropod-borne viruses (arboviruses) chikungunya, dengue, yellow fever and Zika viruses. Vector immune responses pose a major barrier to arboviral transmission, and transgenic insects with altered immunity have been proposed as tools for reducing the global public health impact of arboviral diseases. However, a better understanding of virus-immune interactions is needed to progress the development of such transgenic insects. Although the NF-κB-regulated Toll and ‘immunodeficiency’ (Imd) pathways are increasingly thought to be antiviral, relevant pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) remain poorly characterised in A. aegypti.Methodology/Principle FindingsWe developed novel RT-qPCR and luciferase reporter assays to measure induction of the Toll and Imd pathways in the commonly used A. aegypti-derived Aag2 cell line. We thus determined that the Toll pathway is not inducible by exogenous stimulation with bacterial, viral or fungal stimuli in Aag2 cells under our experimental conditions. We used our Imd pathway-specific assays to demonstrate that the viral dsRNA mimic poly(I:C) is sensed by the Imd pathway, likely through intracellular and extracellular PRRs. The Imd pathway was also induced during infection with the model insect-specific virus cricket paralysis virus (CrPV).Conclusions/SignificanceOur demonstration that a general PAMP shared by many arboviruses is sensed by the Imd pathway paves the way for future studies to determine how viral RNA is sensed by mosquito PRRs at a molecular level. Our data also suggest that studies measuring inducible immune pathway activation through antimicrobial peptide (AMP) expression in Aag2 cells should be interpreted cautiously given that the Toll pathway is not responsive under all experimental conditions. With no antiviral therapies and few effective vaccines available to treat arboviral diseases, our findings provide new insights relevant to the development of transgenic mosquitoes as a means of reducing arbovirus transmission.AUTHOR SUMMARYThe mosquito Aedes aegypti, found globally across the tropics and subtropics, transmits viral diseases with a significant global public health impact, including chikungunya, dengue, yellow fever and Zika viruses. There are no antiviral drugs to treat these diseases and few effective vaccines. One way of reducing the global burden of mosquito-borne diseases would be to develop genetically modified mosquitoes unable to transmit viruses. One approach would be to alter the mosquitoes’ immune system to allow them to better fight viral infections. To do so, we first need to understand how viruses are detected by the mosquito immune system. We developed new methods of measuring immune responses in laboratory-cultured mosquito cells and used them to show that one specific arm of the immune system, called the ‘Imd pathway’, can detect the RNA that constitutes the genome of mosquito-borne viruses. These findings pave the way for future immune studies that could inform the development of transmission-incompetent mosquitoes. We also found that another arm of the immune system, called the ‘Toll pathway’, is not functional under any experimental conditions used in this study. This finding has implications for how different laboratories interpret data from these particular cultured cells.

scholarly journals The Mosquito Immune System and the Life of Dengue Virus: What We Know and Do Not Know

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 77 ◽  
Author(s):  
Debica Mukherjee ◽  
Sandeepan Das ◽  
Feroza Begum ◽  
Sweety Mal ◽  
Upasana Ray
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Aedes Albopictus ◽  
Blood Meal ◽  
Mosquito Vector ◽  
Preventive Strategies ◽  
Immune Control ◽  
The Family

Flaviviruses are largely transmitted to humans by their arthropod vectors such as mosquitoes or ticks. The dengue virus (DENV) is one of the members of the family Flaviviridae and is the causative agent of dengue fever. In the mosquito vector, DENV enters through viremic blood meal and replicates in the mid-gut. Newly formed virion particles circulate to various mosquito organs and get transmitted to the next host in subsequent bites. Aedes aegypti and Aedes albopictus have intricate immune control to allow DENV production at a sub-pathogenic level. In the mosquito, antimicrobial peptides (AMP) and RNA inference (RNAi) are the two main antiviral strategies used against DENV. Apart from innate immunity, mosquito resident microbes play a significant role in modulating DENV replication. In this review, we discuss different immune mechanisms and preventive strategies that act against DENV in two of its vectors: Aedes aegypti and Aedes albopictus.

scholarly journals Erratum to: Nanoparticles in the fight against mosquito-borne diseases: bioactivity of Bruguiera cylindrica-synthesized nanoparticles against dengue virus DEN-2 (in vitro) and its mosquito vector Aedes aegypti (Diptera: Culicidae)

2015 ◽  
Vol 114 (12) ◽  
pp. 4743-4743
Author(s):  
Kadarkarai Murugan ◽  
Devakumar Dinesh ◽  
Manickam Paulpandi ◽  
Abdulaziz Dakhellah Meqbel Althbyani ◽  
Jayapal Subramaniam ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Mosquito Vector ◽  
Bruguiera Cylindrica

Impact of Dengue Virus Infection on Global Metabolic Alterations in the Aedes aegypti Mosquito Vector

2015 ◽  
Vol 2 (4-5) ◽  
pp. 130
Author(s):  
Nunya Chotiwan ◽  
Irma Sanchez-Vargus ◽  
Jeffrey M. Grabowski ◽  
Amber Hopf-jannasch ◽  
Victoria Hedrick ◽  
...  
Keyword(s):  
Virus Infection ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Mosquito Vector ◽  
Dengue Virus Infection ◽  
Metabolic Alterations

Dengue and the introduction of mosquito-transmitted viruses into Australia

2016 ◽  
Vol 37 (4) ◽  
pp. 167
Author(s):  
Andrew F van den Hurk
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Virus Transmission ◽  
Current Situation ◽  
Mosquito Vector ◽  
And Control

Dengue virus outbreaks involving 100s of cases periodically occur in north Queensland, the area of Australia where the primary mosquito vector, Aedes aegypti, occurs. This article summarises the ecology, history, current situation and control of dengue virus transmission in Australia and examines the threat posed by newly emergent arboviruses, such as Zika and chikungunya viruses.

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