Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System
Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3523 |
| _version_ | 1797240666501152768 |
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| author | Shigenori Sasaki Hirohito Ogawa Hirokazu Katoh Tomoyuki Honda |
| author_facet | Shigenori Sasaki Hirohito Ogawa Hirokazu Katoh Tomoyuki Honda |
| author_sort | Shigenori Sasaki |
| collection | DOAJ |
| description | Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are lost by BoDV-1 infection, it is difficult to regenerate damaged neural networks. Therefore, the development of efficient anti-BoDV-1 treatments is important to improve the outcomes of the infection. Recently, one of the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) systems, CRISPR/Cas13, has been utilized as antiviral tools. However, it is still unrevealed whether the CRISPR/Cas13 system can suppress RNA viruses in persistently infected cells. In this study, we addressed this question using persistently BoDV-1-infected cells. The CRISPR/Cas13 system targeting viral mRNAs efficiently decreased the levels of target viral mRNAs and genomic RNA (gRNA) in persistently infected cells. Furthermore, the CRISPR/Cas13 system targeting viral mRNAs also suppressed BoDV-1 infection if the system was introduced prior to the infection. Collectively, we demonstrated that the CRISPR/Cas13 system can suppress BoDV-1 in both acute and persistent infections. Our findings will open the avenue to treat prolonged infection with RNA viruses using the CRISPR/Cas13 system. |
| first_indexed | 2024-04-24T18:11:04Z |
| format | Article |
| id | doaj.art-28abac7c66c24b25a937f8e6112f5a9d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T18:11:04Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-28abac7c66c24b25a937f8e6112f5a9d2024-03-27T13:46:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256352310.3390/ijms25063523Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b SystemShigenori Sasaki0Hirohito Ogawa1Hirokazu Katoh2Tomoyuki Honda3Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Virology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanBorna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are lost by BoDV-1 infection, it is difficult to regenerate damaged neural networks. Therefore, the development of efficient anti-BoDV-1 treatments is important to improve the outcomes of the infection. Recently, one of the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) systems, CRISPR/Cas13, has been utilized as antiviral tools. However, it is still unrevealed whether the CRISPR/Cas13 system can suppress RNA viruses in persistently infected cells. In this study, we addressed this question using persistently BoDV-1-infected cells. The CRISPR/Cas13 system targeting viral mRNAs efficiently decreased the levels of target viral mRNAs and genomic RNA (gRNA) in persistently infected cells. Furthermore, the CRISPR/Cas13 system targeting viral mRNAs also suppressed BoDV-1 infection if the system was introduced prior to the infection. Collectively, we demonstrated that the CRISPR/Cas13 system can suppress BoDV-1 in both acute and persistent infections. Our findings will open the avenue to treat prolonged infection with RNA viruses using the CRISPR/Cas13 system.https://www.mdpi.com/1422-0067/25/6/3523antiviralantiviralsBorna disease virusCRISPR/Cas13bpersistent infection |
| spellingShingle | Shigenori Sasaki Hirohito Ogawa Hirokazu Katoh Tomoyuki Honda Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System International Journal of Molecular Sciences antiviral antivirals Borna disease virus CRISPR/Cas13b persistent infection |
| title | Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System |
| title_full | Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System |
| title_fullStr | Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System |
| title_full_unstemmed | Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System |
| title_short | Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System |
| title_sort | suppression of borna disease virus replication during its persistent infection using the crispr cas13b system |
| topic | antiviral antivirals Borna disease virus CRISPR/Cas13b persistent infection |
| url | https://www.mdpi.com/1422-0067/25/6/3523 |
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