An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti
ABSTRACT Chikungunya virus (CHIKV) is a reemerging alphavirus causing chikungunya disease (CHIKD) and is transmitted to humans by Aedes mosquitoes. The virus establishes an intricate balance of cellular interactions that ultimately helps in its replication and dodges cellular immune response. In an...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00595-22 |
| _version_ | 1818218484927037440 |
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| author | Sunil Kumar Dubey Divya Mehta Sakshi Chaudhary Abdul Hasan Sujatha Sunil |
| author_facet | Sunil Kumar Dubey Divya Mehta Sakshi Chaudhary Abdul Hasan Sujatha Sunil |
| author_sort | Sunil Kumar Dubey |
| collection | DOAJ |
| description | ABSTRACT Chikungunya virus (CHIKV) is a reemerging alphavirus causing chikungunya disease (CHIKD) and is transmitted to humans by Aedes mosquitoes. The virus establishes an intricate balance of cellular interactions that ultimately helps in its replication and dodges cellular immune response. In an attempt to identify cellular host factors required during CHIKV replication in Aag2 cells, we performed global transcriptomics of CHIKV-infected Aag2 cells, and further, we compared this library with the Drosophila RNAi Screening Center (DRSC) database and identified transcripts that were regulated in Aedes aegypti during CHIKV infection. These analyses revealed specific pathways, such as ubiquitin-related pathways, proteolysis pathways, protein catabolic processes, protein modification, and cellular protein metabolic processes, involved during replication of the virus. Loss-of-function assays of selected candidates revealed their proviral or antiviral characteristics upon CHIKV infection in A. aegypti-derived Aag2 cells. Further validations identified that the ubiquitin proteasomal pathway is required for CHIKV infection in A. aegypti and that an important member of this family of proteins, namely, AeCullin-3 (Aedes ortholog of human cullin-3), is a proviral host factor of CHIKV replication in Aag2 cells. IMPORTANCE Arboviruses cause several diseases in humans and livestock. Vector control is the main strategy for controlling diseases transmitted by mosquitoes. In this context, it becomes paramount to understand how the viruses replicate in the vector for designing better transmission blocking strategies. We obtained the global transcriptome signature of A. aegypti cells during CHIKV infection, and in order to obtain the maximum information from these data sets, we further utilized the well-characterized Drosophila system and arrived upon a set of transcripts and their pathways that affect A. aegypti cells during CHIKV infection. These analyses and further validations reveal that important pathways related to protein degradation are actively involved during CHIKV infection in A. aegypti and are mainly proviral. Targeting these molecules may provide novel approaches for blocking CHIKV replication in A. aegypti. |
| first_indexed | 2024-12-12T07:24:30Z |
| format | Article |
| id | doaj.art-1befc9ebe856457c85abc5e49851ed77 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-12T07:24:30Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-1befc9ebe856457c85abc5e49851ed772022-12-22T00:33:11ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.00595-22An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegyptiSunil Kumar Dubey0Divya Mehta1Sakshi Chaudhary2Abdul Hasan3Sujatha Sunil4Vector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, IndiaVector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, IndiaVector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, IndiaVector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, IndiaVector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, IndiaABSTRACT Chikungunya virus (CHIKV) is a reemerging alphavirus causing chikungunya disease (CHIKD) and is transmitted to humans by Aedes mosquitoes. The virus establishes an intricate balance of cellular interactions that ultimately helps in its replication and dodges cellular immune response. In an attempt to identify cellular host factors required during CHIKV replication in Aag2 cells, we performed global transcriptomics of CHIKV-infected Aag2 cells, and further, we compared this library with the Drosophila RNAi Screening Center (DRSC) database and identified transcripts that were regulated in Aedes aegypti during CHIKV infection. These analyses revealed specific pathways, such as ubiquitin-related pathways, proteolysis pathways, protein catabolic processes, protein modification, and cellular protein metabolic processes, involved during replication of the virus. Loss-of-function assays of selected candidates revealed their proviral or antiviral characteristics upon CHIKV infection in A. aegypti-derived Aag2 cells. Further validations identified that the ubiquitin proteasomal pathway is required for CHIKV infection in A. aegypti and that an important member of this family of proteins, namely, AeCullin-3 (Aedes ortholog of human cullin-3), is a proviral host factor of CHIKV replication in Aag2 cells. IMPORTANCE Arboviruses cause several diseases in humans and livestock. Vector control is the main strategy for controlling diseases transmitted by mosquitoes. In this context, it becomes paramount to understand how the viruses replicate in the vector for designing better transmission blocking strategies. We obtained the global transcriptome signature of A. aegypti cells during CHIKV infection, and in order to obtain the maximum information from these data sets, we further utilized the well-characterized Drosophila system and arrived upon a set of transcripts and their pathways that affect A. aegypti cells during CHIKV infection. These analyses and further validations reveal that important pathways related to protein degradation are actively involved during CHIKV infection in A. aegypti and are mainly proviral. Targeting these molecules may provide novel approaches for blocking CHIKV replication in A. aegypti.https://journals.asm.org/doi/10.1128/spectrum.00595-22Chikungunya virusAedes aegyptivector–virus interactionsubiquitin proteasomal pathway |
| spellingShingle | Sunil Kumar Dubey Divya Mehta Sakshi Chaudhary Abdul Hasan Sujatha Sunil An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti Microbiology Spectrum Chikungunya virus Aedes aegypti vector–virus interactions ubiquitin proteasomal pathway |
| title | An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti |
| title_full | An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti |
| title_fullStr | An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti |
| title_full_unstemmed | An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti |
| title_short | An E3 Ubiquitin Ligase Scaffolding Protein Is Proviral during Chikungunya Virus Infection in Aedes aegypti |
| title_sort | e3 ubiquitin ligase scaffolding protein is proviral during chikungunya virus infection in aedes aegypti |
| topic | Chikungunya virus Aedes aegypti vector–virus interactions ubiquitin proteasomal pathway |
| url | https://journals.asm.org/doi/10.1128/spectrum.00595-22 |
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