Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease

Abstract Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately 4 billion people at risk of arthropod-borne...

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Main Authors: Stephanie French, Rachael Da Silva, Janet Storm, Christida E. Wastika, India Cullen, Martijn ten Have, Grant L. Hughes, Cassandra M. Modahl
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Parasites & Vectors
Subjects:
Online Access:https://doi.org/10.1186/s13071-025-06663-9
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author Stephanie French
Rachael Da Silva
Janet Storm
Christida E. Wastika
India Cullen
Martijn ten Have
Grant L. Hughes
Cassandra M. Modahl
author_facet Stephanie French
Rachael Da Silva
Janet Storm
Christida E. Wastika
India Cullen
Martijn ten Have
Grant L. Hughes
Cassandra M. Modahl
author_sort Stephanie French
collection DOAJ
description Abstract Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately 4 billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing. Mosquito symbionts, including fungi, bacteria and viruses, have desirable traits for mosquito disease control including spreading horizontally and vertically through mosquito populations and potentially colonising multiple important vector species. Paratransgenesis, genetic modification of mosquito symbionts with effectors to target the pathogen rather than the vector, is a promising strategy to prevent the spread of mosquito-borne diseases. A variety of effectors can be expressed but venom toxins are excellent effector candidates because they are target specific, potent and stable. However, the only toxins to be explored in mosquito paratransgenesis to date are scorpine and mutated phospholipase A2. To enhance the scope, effectiveness and durability of paratransgenesis, an expanded arsenal of effectors is required. This review discusses other potential toxin effectors for future paratransgenesis studies based on prior in vitro and in vivo antiparasitic and antiviral studies and highlights the need for further research and investment in this area. In terms of mosquito-borne diseases, paratransgenesis strategies have been developed to target Plasmodium. We postulate the potential to apply this principle to target arboviruses using antiviral toxin effectors. Graphical Abstract
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spelling doaj-art-aa923740694245b1afeeadeb0909d2ea2025-02-02T12:11:07ZengBMCParasites & Vectors1756-33052025-01-011811910.1186/s13071-025-06663-9Exploiting venom toxins in paratransgenesis to prevent mosquito-borne diseaseStephanie French0Rachael Da Silva1Janet Storm2Christida E. Wastika3India Cullen4Martijn ten Have5Grant L. Hughes6Cassandra M. Modahl7Centre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineDepartments of Vector Biology and Tropical Disease Biology, Centre for Neglected Tropical Disease, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineDepartments of Vector Biology and Tropical Disease Biology, Centre for Neglected Tropical Disease, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineAbstract Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately 4 billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing. Mosquito symbionts, including fungi, bacteria and viruses, have desirable traits for mosquito disease control including spreading horizontally and vertically through mosquito populations and potentially colonising multiple important vector species. Paratransgenesis, genetic modification of mosquito symbionts with effectors to target the pathogen rather than the vector, is a promising strategy to prevent the spread of mosquito-borne diseases. A variety of effectors can be expressed but venom toxins are excellent effector candidates because they are target specific, potent and stable. However, the only toxins to be explored in mosquito paratransgenesis to date are scorpine and mutated phospholipase A2. To enhance the scope, effectiveness and durability of paratransgenesis, an expanded arsenal of effectors is required. This review discusses other potential toxin effectors for future paratransgenesis studies based on prior in vitro and in vivo antiparasitic and antiviral studies and highlights the need for further research and investment in this area. In terms of mosquito-borne diseases, paratransgenesis strategies have been developed to target Plasmodium. We postulate the potential to apply this principle to target arboviruses using antiviral toxin effectors. Graphical Abstracthttps://doi.org/10.1186/s13071-025-06663-9Rift Valley fever virusYellow fever virusJapanese encephalitis virusWest Nile virusChikungunya virusDengue virus
spellingShingle Stephanie French
Rachael Da Silva
Janet Storm
Christida E. Wastika
India Cullen
Martijn ten Have
Grant L. Hughes
Cassandra M. Modahl
Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease
Parasites & Vectors
Rift Valley fever virus
Yellow fever virus
Japanese encephalitis virus
West Nile virus
Chikungunya virus
Dengue virus
title Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease
title_full Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease
title_fullStr Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease
title_full_unstemmed Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease
title_short Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease
title_sort exploiting venom toxins in paratransgenesis to prevent mosquito borne disease
topic Rift Valley fever virus
Yellow fever virus
Japanese encephalitis virus
West Nile virus
Chikungunya virus
Dengue virus
url https://doi.org/10.1186/s13071-025-06663-9
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