Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication.
<h4>Background</h4>RNA interference is among the most important mechanisms that serve to restrict virus replication within mosquitoes, where microRNAs (miRNAs) are important in regulating viral replication and cellular functions. These miRNAs function by binding to complementary sequence...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-06-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0007429 |
| _version_ | 1797351489176338432 |
|---|---|
| author | Sunil Kumar Dubey Jatin Shrinet Sujatha Sunil |
| author_facet | Sunil Kumar Dubey Jatin Shrinet Sujatha Sunil |
| author_sort | Sunil Kumar Dubey |
| collection | DOAJ |
| description | <h4>Background</h4>RNA interference is among the most important mechanisms that serve to restrict virus replication within mosquitoes, where microRNAs (miRNAs) are important in regulating viral replication and cellular functions. These miRNAs function by binding to complementary sequences mostly in the untranslated regions of the target. Chikungunya virus (CHIKV) genome consists of two open reading frames flanked by 5' and 3' untranslated regions on the two sides. A recent study from our laboratory has shown that Aedes miRNAs are regulated during CHIKV infection. The present study was undertaken to further understand the role of these miRNAs in CHIKV replication.<h4>Methods/findings</h4>We observe that miR-2944b-5p binds to the 3' untranslated region of CHIKV and the binding is abated when the binding sites are abolished. Loss-of-function studies of miR-2944b-5p using antagomirs, both in vitro and in vivo, reveal an increase in CHIKV viral replication, thereby directly implying a role of miR-2944b-5p in CHIKV replication. We further showed that the mitochondrial membrane potential of the mosquito cells is maintained by this miRNA during CHIKV replication, and cellular factor vps-13 plays a contributing role.<h4>Conclusions</h4>Our study has opened new avenues to understand vector-virus interactions and provides novel insights into CHIKV replication in Aedes aegypti. Furthermore, our study has shown miR-2944b-5p to be playing role, where one of its target vps-13 also contributes, in maintaining mitochondrial membrane potential in Aedes aegypti. |
| first_indexed | 2024-03-08T13:01:11Z |
| format | Article |
| id | doaj.art-5c611f481eec4f53876bae012f9060f3 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-03-08T13:01:11Z |
| publishDate | 2019-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-5c611f481eec4f53876bae012f9060f32024-01-19T05:48:13ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352019-06-01136e000742910.1371/journal.pntd.0007429Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication.Sunil Kumar DubeyJatin ShrinetSujatha Sunil<h4>Background</h4>RNA interference is among the most important mechanisms that serve to restrict virus replication within mosquitoes, where microRNAs (miRNAs) are important in regulating viral replication and cellular functions. These miRNAs function by binding to complementary sequences mostly in the untranslated regions of the target. Chikungunya virus (CHIKV) genome consists of two open reading frames flanked by 5' and 3' untranslated regions on the two sides. A recent study from our laboratory has shown that Aedes miRNAs are regulated during CHIKV infection. The present study was undertaken to further understand the role of these miRNAs in CHIKV replication.<h4>Methods/findings</h4>We observe that miR-2944b-5p binds to the 3' untranslated region of CHIKV and the binding is abated when the binding sites are abolished. Loss-of-function studies of miR-2944b-5p using antagomirs, both in vitro and in vivo, reveal an increase in CHIKV viral replication, thereby directly implying a role of miR-2944b-5p in CHIKV replication. We further showed that the mitochondrial membrane potential of the mosquito cells is maintained by this miRNA during CHIKV replication, and cellular factor vps-13 plays a contributing role.<h4>Conclusions</h4>Our study has opened new avenues to understand vector-virus interactions and provides novel insights into CHIKV replication in Aedes aegypti. Furthermore, our study has shown miR-2944b-5p to be playing role, where one of its target vps-13 also contributes, in maintaining mitochondrial membrane potential in Aedes aegypti.https://doi.org/10.1371/journal.pntd.0007429 |
| spellingShingle | Sunil Kumar Dubey Jatin Shrinet Sujatha Sunil Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication. PLoS Neglected Tropical Diseases |
| title | Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication. |
| title_full | Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication. |
| title_fullStr | Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication. |
| title_full_unstemmed | Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication. |
| title_short | Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication. |
| title_sort | aedes aegypti microrna mir 2944b 5p interacts with 3 utr of chikungunya virus and cellular target vps 13 to regulate viral replication |
| url | https://doi.org/10.1371/journal.pntd.0007429 |
| work_keys_str_mv | AT sunilkumardubey aedesaegyptimicrornamir2944b5pinteractswith3utrofchikungunyavirusandcellulartargetvps13toregulateviralreplication AT jatinshrinet aedesaegyptimicrornamir2944b5pinteractswith3utrofchikungunyavirusandcellulartargetvps13toregulateviralreplication AT sujathasunil aedesaegyptimicrornamir2944b5pinteractswith3utrofchikungunyavirusandcellulartargetvps13toregulateviralreplication |