Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements
Aedes aegypti transmit pathogenic arboviruses while the mosquito itself tolerates the infection. We examine a piRNA-based immunity that relies on the acquisition of viral derived cDNA (vDNA) and how this pathway discriminates between self and non-self. The piRNAs derived from these vDNAs are essenti...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/41244 |
| _version_ | 1811199643860598784 |
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| author | Michel Tassetto Mark Kunitomi Zachary J Whitfield Patrick T Dolan Irma Sánchez-Vargas Miguel Garcia-Knight Isabel Ribiero Taotao Chen Ken E Olson Raul Andino |
| author_facet | Michel Tassetto Mark Kunitomi Zachary J Whitfield Patrick T Dolan Irma Sánchez-Vargas Miguel Garcia-Knight Isabel Ribiero Taotao Chen Ken E Olson Raul Andino |
| author_sort | Michel Tassetto |
| collection | DOAJ |
| description | Aedes aegypti transmit pathogenic arboviruses while the mosquito itself tolerates the infection. We examine a piRNA-based immunity that relies on the acquisition of viral derived cDNA (vDNA) and how this pathway discriminates between self and non-self. The piRNAs derived from these vDNAs are essential for virus control and Piwi4 has a central role in the pathway. Piwi4 binds preferentially to virus-derived piRNAs but not to transposon-targeting piRNAs. Analysis of episomal vDNA from infected cells reveals that vDNA molecules are acquired through a discriminatory process of reverse-transcription and recombination directed by endogenous retrotransposons. Using a high-resolution Ae. aegypti genomic sequence, we found that vDNAs integrated in the host genome as endogenous viral elements (EVEs), produce antisense piRNAs that are preferentially loaded onto Piwi4. Importantly, EVE-derived piRNAs are specifically loaded onto Piwi4 to inhibit virus replication. Thus, Ae. aegypti employs a sophisticated antiviral mechanism that promotes viral persistence and generates long-lasting adaptive immunity. |
| first_indexed | 2024-04-12T01:51:00Z |
| format | Article |
| id | doaj.art-ea7842ae357541ff9c9984e3ebe0a05e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:51:00Z |
| publishDate | 2019-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ea7842ae357541ff9c9984e3ebe0a05e2022-12-22T03:52:56ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.41244Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elementsMichel Tassetto0https://orcid.org/0000-0001-5666-8796Mark Kunitomi1https://orcid.org/0000-0002-4626-8972Zachary J Whitfield2https://orcid.org/0000-0001-9965-428XPatrick T Dolan3https://orcid.org/0000-0002-4169-0058Irma Sánchez-Vargas4Miguel Garcia-Knight5Isabel Ribiero6Taotao Chen7Ken E Olson8https://orcid.org/0000-0002-3135-4878Raul Andino9https://orcid.org/0000-0001-5503-9349Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Microbiology, Immunology and Pathology, Arthropod-borne and Infectious Diseases Laboratory, Colorado State University, Fort Collins, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Microbiology, Immunology and Pathology, Arthropod-borne and Infectious Diseases Laboratory, Colorado State University, Fort Collins, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesAedes aegypti transmit pathogenic arboviruses while the mosquito itself tolerates the infection. We examine a piRNA-based immunity that relies on the acquisition of viral derived cDNA (vDNA) and how this pathway discriminates between self and non-self. The piRNAs derived from these vDNAs are essential for virus control and Piwi4 has a central role in the pathway. Piwi4 binds preferentially to virus-derived piRNAs but not to transposon-targeting piRNAs. Analysis of episomal vDNA from infected cells reveals that vDNA molecules are acquired through a discriminatory process of reverse-transcription and recombination directed by endogenous retrotransposons. Using a high-resolution Ae. aegypti genomic sequence, we found that vDNAs integrated in the host genome as endogenous viral elements (EVEs), produce antisense piRNAs that are preferentially loaded onto Piwi4. Importantly, EVE-derived piRNAs are specifically loaded onto Piwi4 to inhibit virus replication. Thus, Ae. aegypti employs a sophisticated antiviral mechanism that promotes viral persistence and generates long-lasting adaptive immunity.https://elifesciences.org/articles/41244adaptive immunitymosquito vectortolerance to infectionself-nonself discriminationRNA virusesendogenous retroviruses |
| spellingShingle | Michel Tassetto Mark Kunitomi Zachary J Whitfield Patrick T Dolan Irma Sánchez-Vargas Miguel Garcia-Knight Isabel Ribiero Taotao Chen Ken E Olson Raul Andino Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements eLife adaptive immunity mosquito vector tolerance to infection self-nonself discrimination RNA viruses endogenous retroviruses |
| title | Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements |
| title_full | Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements |
| title_fullStr | Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements |
| title_full_unstemmed | Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements |
| title_short | Control of RNA viruses in mosquito cells through the acquisition of vDNA and endogenous viral elements |
| title_sort | control of rna viruses in mosquito cells through the acquisition of vdna and endogenous viral elements |
| topic | adaptive immunity mosquito vector tolerance to infection self-nonself discrimination RNA viruses endogenous retroviruses |
| url | https://elifesciences.org/articles/41244 |
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