Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes
Abstract Background Arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, the Aedes aegypti mos...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-025-02325-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849331560706211840 |
|---|---|
| author | Elodie Couderc Anna B. Crist Josquin Daron Hugo Varet Femke A. H. van Hout Pascal Miesen Umberto Palatini Stéphanie Dabo Thomas Vial Louis Lambrechts Sarah H. Merkling |
| author_facet | Elodie Couderc Anna B. Crist Josquin Daron Hugo Varet Femke A. H. van Hout Pascal Miesen Umberto Palatini Stéphanie Dabo Thomas Vial Louis Lambrechts Sarah H. Merkling |
| author_sort | Elodie Couderc |
| collection | DOAJ |
| description | Abstract Background Arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, the Aedes aegypti mosquito. In arthropods, genes of the Vago family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of Vago genes upon virus infection in Ae. aegypti is largely unknown. Results We conducted a phylogenetic analysis of the Vago gene family in Diptera, which led us to focus on a Vago-like gene that we named VLG-1. Using CRISPR/Cas9-mediated gene editing, we generated a VLG-1 mutant line of Ae. aegypti, which revealed a broad impact of VLG-1 on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the VLG-1 mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of VLG-1, virus dissemination throughout the mosquito’s body was slightly impaired, albeit not altering virus transmission rates. Conclusions Our results challenge the conventional understanding of Vago-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions. |
| format | Article |
| id | doaj-art-6d71e62d1d5847ce9d863a096418e95d |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-6d71e62d1d5847ce9d863a096418e95d2025-08-20T03:46:29ZengBMCBMC Biology1741-70072025-07-0123111910.1186/s12915-025-02325-5Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genesElodie Couderc0Anna B. Crist1Josquin Daron2Hugo Varet3Femke A. H. van Hout4Pascal Miesen5Umberto Palatini6Stéphanie Dabo7Thomas Vial8Louis Lambrechts9Sarah H. Merkling10Institut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions UnitInstitut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions UnitInstitut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions UnitBioinformatics and Biostatistics Hub, Institut Pasteur, Université Paris CitéDepartment of Medical Microbiology, Radboud University Medical CenterDepartment of Medical Microbiology, Radboud University Medical CenterInstitut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions UnitInstitut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions UnitInstitut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions UnitInstitut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions UnitInstitut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions UnitAbstract Background Arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, the Aedes aegypti mosquito. In arthropods, genes of the Vago family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of Vago genes upon virus infection in Ae. aegypti is largely unknown. Results We conducted a phylogenetic analysis of the Vago gene family in Diptera, which led us to focus on a Vago-like gene that we named VLG-1. Using CRISPR/Cas9-mediated gene editing, we generated a VLG-1 mutant line of Ae. aegypti, which revealed a broad impact of VLG-1 on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the VLG-1 mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of VLG-1, virus dissemination throughout the mosquito’s body was slightly impaired, albeit not altering virus transmission rates. Conclusions Our results challenge the conventional understanding of Vago-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.https://doi.org/10.1186/s12915-025-02325-5Aedes aegyptiVagoFlavivirusDengue virusVector competenceAntiviral factor |
| spellingShingle | Elodie Couderc Anna B. Crist Josquin Daron Hugo Varet Femke A. H. van Hout Pascal Miesen Umberto Palatini Stéphanie Dabo Thomas Vial Louis Lambrechts Sarah H. Merkling Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes BMC Biology Aedes aegypti Vago Flavivirus Dengue virus Vector competence Antiviral factor |
| title | Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes |
| title_full | Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes |
| title_fullStr | Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes |
| title_full_unstemmed | Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes |
| title_short | Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes |
| title_sort | aedes aegypti vlg 1 challenges the assumed antiviral nature of vago genes |
| topic | Aedes aegypti Vago Flavivirus Dengue virus Vector competence Antiviral factor |
| url | https://doi.org/10.1186/s12915-025-02325-5 |
| work_keys_str_mv | AT elodiecouderc aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT annabcrist aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT josquindaron aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT hugovaret aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT femkeahvanhout aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT pascalmiesen aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT umbertopalatini aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT stephaniedabo aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT thomasvial aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT louislambrechts aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes AT sarahhmerkling aedesaegyptivlg1challengestheassumedantiviralnatureofvagogenes |