Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut.
Dengue virus (DENV) causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vecto...
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ftdoajarticles:oai:doaj.org/article:41667392d3da4acf801ab93126b39219 2023-05-15T15:11:58+02:00 Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut. Vincent Raquin Sarah Hélène Merkling Valérie Gausson Isabelle Moltini-Conclois Lionel Frangeul Hugo Varet Marie-Agnès Dillies Maria-Carla Saleh Louis Lambrechts 2017-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006152 https://doaj.org/article/41667392d3da4acf801ab93126b39219 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0006152 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006152 https://doaj.org/article/41667392d3da4acf801ab93126b39219 PLoS Neglected Tropical Diseases, Vol 11, Iss 12, p e0006152 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006152 2022-12-31T11:56:29Z Dengue virus (DENV) causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vector Aedes aegypti used inbred laboratory colonies and/or pools of mosquitoes that erase individual variation. Here, we performed transcriptome sequencing on individual midguts in a field-derived Ae. aegypti population to identify new candidate host factors modulating DENV replication. We analyzed the transcriptomic data using an approach that accounts for individual co-variation between viral RNA load and gene expression. This approach generates a prediction about the agonist or antagonist effect of candidate genes on DENV replication based on the sign of the correlation between gene expression and viral RNA load. Using this method, we identified 39 candidate genes that went undetected by conventional pairwise comparison of gene expression levels between DENV-infected midguts and uninfected controls. Only four candidate genes were detected by both methods, emphasizing their complementarity. We demonstrated the value of our approach by functional validation of a candidate agonist gene encoding a sterol regulatory element-binding protein (SREBP), which was identified by correlation analysis but not by pairwise comparison. We confirmed that SREBP promotes DENV infection in the midgut by RNAi-mediated gene knockdown in vivo. We suggest that our approach for transcriptomic analysis can empower genome-wide screens for potential agonist or antagonist factors by leveraging inter-individual variation in gene expression. More generally, this method is applicable to a wide range of phenotypic traits displaying inter-individual variation. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 12 e0006152 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Vincent Raquin Sarah Hélène Merkling Valérie Gausson Isabelle Moltini-Conclois Lionel Frangeul Hugo Varet Marie-Agnès Dillies Maria-Carla Saleh Louis Lambrechts Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Dengue virus (DENV) causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vector Aedes aegypti used inbred laboratory colonies and/or pools of mosquitoes that erase individual variation. Here, we performed transcriptome sequencing on individual midguts in a field-derived Ae. aegypti population to identify new candidate host factors modulating DENV replication. We analyzed the transcriptomic data using an approach that accounts for individual co-variation between viral RNA load and gene expression. This approach generates a prediction about the agonist or antagonist effect of candidate genes on DENV replication based on the sign of the correlation between gene expression and viral RNA load. Using this method, we identified 39 candidate genes that went undetected by conventional pairwise comparison of gene expression levels between DENV-infected midguts and uninfected controls. Only four candidate genes were detected by both methods, emphasizing their complementarity. We demonstrated the value of our approach by functional validation of a candidate agonist gene encoding a sterol regulatory element-binding protein (SREBP), which was identified by correlation analysis but not by pairwise comparison. We confirmed that SREBP promotes DENV infection in the midgut by RNAi-mediated gene knockdown in vivo. We suggest that our approach for transcriptomic analysis can empower genome-wide screens for potential agonist or antagonist factors by leveraging inter-individual variation in gene expression. More generally, this method is applicable to a wide range of phenotypic traits displaying inter-individual variation. |
format |
Article in Journal/Newspaper |
author |
Vincent Raquin Sarah Hélène Merkling Valérie Gausson Isabelle Moltini-Conclois Lionel Frangeul Hugo Varet Marie-Agnès Dillies Maria-Carla Saleh Louis Lambrechts |
author_facet |
Vincent Raquin Sarah Hélène Merkling Valérie Gausson Isabelle Moltini-Conclois Lionel Frangeul Hugo Varet Marie-Agnès Dillies Maria-Carla Saleh Louis Lambrechts |
author_sort |
Vincent Raquin |
title |
Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut. |
title_short |
Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut. |
title_full |
Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut. |
title_fullStr |
Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut. |
title_full_unstemmed |
Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut. |
title_sort |
individual co-variation between viral rna load and gene expression reveals novel host factors during early dengue virus infection of the aedes aegypti midgut. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0006152 https://doaj.org/article/41667392d3da4acf801ab93126b39219 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 12, p e0006152 (2017) |
op_relation |
https://doi.org/10.1371/journal.pntd.0006152 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006152 https://doaj.org/article/41667392d3da4acf801ab93126b39219 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006152 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
12 |
container_start_page |
e0006152 |
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1766342739036733440 |