Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality
Abstract Ae. aegypti mosquitoes transmit some of the most important human viral diseases that are responsible for a significant public health burden worldwide. The small interfering RNA (siRNA) pathway is considered the major antiviral defense system in insects. Here we show that siRNA pathway disru...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41370-y |
| _version_ | 1797558593973649408 |
|---|---|
| author | Shengzhang Dong George Dimopoulos |
| author_facet | Shengzhang Dong George Dimopoulos |
| author_sort | Shengzhang Dong |
| collection | DOAJ |
| description | Abstract Ae. aegypti mosquitoes transmit some of the most important human viral diseases that are responsible for a significant public health burden worldwide. The small interfering RNA (siRNA) pathway is considered the major antiviral defense system in insects. Here we show that siRNA pathway disruption by CRISPR/Cas9-based Ago2 knockout impaired the mosquitoes’ ability to degrade arbovirus RNA leading to hyper-infection accompanied by cell lysis and tissue damage. Ago2 disruption impaired DNA repair mechanisms and the autophagy pathway by altering histone abundance. This compromised DNA repair and removal of damaged cellular organelles and dysfunctional aggregates promoted mosquito death. We also report that hyper-infection of Ago2 knockout mosquitoes stimulated a broad-spectrum antiviral immunity, including apoptosis, which may counteract infection. Taken together, our studies reveal novel roles for Ago2 in protecting mosquitoes from arbovirus infection and associated death. |
| first_indexed | 2024-03-10T17:32:42Z |
| format | Article |
| id | doaj.art-82fd85d8d55c4fb783602bf39c4c3b28 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:32:42Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-82fd85d8d55c4fb783602bf39c4c3b282023-11-20T09:57:24ZengNature PortfolioNature Communications2041-17232023-09-0114111610.1038/s41467-023-41370-yAedes aegypti Argonaute 2 controls arbovirus infection and host mortalityShengzhang Dong0George Dimopoulos1W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins UniversityW. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins UniversityAbstract Ae. aegypti mosquitoes transmit some of the most important human viral diseases that are responsible for a significant public health burden worldwide. The small interfering RNA (siRNA) pathway is considered the major antiviral defense system in insects. Here we show that siRNA pathway disruption by CRISPR/Cas9-based Ago2 knockout impaired the mosquitoes’ ability to degrade arbovirus RNA leading to hyper-infection accompanied by cell lysis and tissue damage. Ago2 disruption impaired DNA repair mechanisms and the autophagy pathway by altering histone abundance. This compromised DNA repair and removal of damaged cellular organelles and dysfunctional aggregates promoted mosquito death. We also report that hyper-infection of Ago2 knockout mosquitoes stimulated a broad-spectrum antiviral immunity, including apoptosis, which may counteract infection. Taken together, our studies reveal novel roles for Ago2 in protecting mosquitoes from arbovirus infection and associated death.https://doi.org/10.1038/s41467-023-41370-y |
| spellingShingle | Shengzhang Dong George Dimopoulos Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality Nature Communications |
| title | Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality |
| title_full | Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality |
| title_fullStr | Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality |
| title_full_unstemmed | Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality |
| title_short | Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality |
| title_sort | aedes aegypti argonaute 2 controls arbovirus infection and host mortality |
| url | https://doi.org/10.1038/s41467-023-41370-y |
| work_keys_str_mv | AT shengzhangdong aedesaegyptiargonaute2controlsarbovirusinfectionandhostmortality AT georgedimopoulos aedesaegyptiargonaute2controlsarbovirusinfectionandhostmortality |