Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication
Abstract Circular RNAs (circRNAs) are a family of non-coding RNAs that originate from a non-canonical splicing event (backsplicing) that forms covalently closed continuous loops. An analysis of the human immunodeficiency type 1 virus (HIV-1) complex splicing pattern indicated that the virus had the...
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Nature Portfolio
2025-03-01
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| Series: | npj Viruses |
| Online Access: | https://doi.org/10.1038/s44298-025-00105-0 |
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| author | Christopher Mauer Sean Paz Massimo Caputi |
| author_facet | Christopher Mauer Sean Paz Massimo Caputi |
| author_sort | Christopher Mauer |
| collection | DOAJ |
| description | Abstract Circular RNAs (circRNAs) are a family of non-coding RNAs that originate from a non-canonical splicing event (backsplicing) that forms covalently closed continuous loops. An analysis of the human immunodeficiency type 1 virus (HIV-1) complex splicing pattern indicated that the virus had the potential to generate at least 15 distinct circRNAs. The predicted HIV circRNAs were amplified utilizing divergent PCR primers and confirmed by RNase R digestion and sequencing. A predictive circRNA-miRNA interaction modeling approach and a series of validation assays determined that two cellular miRNAs, miR-6727-3p and miR-4722-3p, functionally interact with a sequence present in 8 of the HIV circRNAs. Expression of miR-6727-3p and miR-4722-3p restricted HIV-1 replication while a circRNA containing the sequence recognized by miR-6727-3p and miR-4722-3p increased the production of infective virions. Additionally, miR-6727-3p and miR-4722-3p expression was upregulated following HIV-1 infection of primary CD4+ T cells. Overall, the data presented shows that HIV-1 generates circRNAs which promote viral replication by sequestering and inhibiting the functions of miR-6727-3p and miR-4722-3p. |
| format | Article |
| id | doaj-art-c90bdeb51bcf49b395bd0fe2d3630e41 |
| institution | DOAJ |
| issn | 2948-1767 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Viruses |
| spelling | doaj-art-c90bdeb51bcf49b395bd0fe2d3630e412025-08-20T02:49:31ZengNature Portfolionpj Viruses2948-17672025-03-013111110.1038/s44298-025-00105-0Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replicationChristopher Mauer0Sean Paz1Massimo Caputi2Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic UniversityDepartment of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic UniversityDepartment of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic UniversityAbstract Circular RNAs (circRNAs) are a family of non-coding RNAs that originate from a non-canonical splicing event (backsplicing) that forms covalently closed continuous loops. An analysis of the human immunodeficiency type 1 virus (HIV-1) complex splicing pattern indicated that the virus had the potential to generate at least 15 distinct circRNAs. The predicted HIV circRNAs were amplified utilizing divergent PCR primers and confirmed by RNase R digestion and sequencing. A predictive circRNA-miRNA interaction modeling approach and a series of validation assays determined that two cellular miRNAs, miR-6727-3p and miR-4722-3p, functionally interact with a sequence present in 8 of the HIV circRNAs. Expression of miR-6727-3p and miR-4722-3p restricted HIV-1 replication while a circRNA containing the sequence recognized by miR-6727-3p and miR-4722-3p increased the production of infective virions. Additionally, miR-6727-3p and miR-4722-3p expression was upregulated following HIV-1 infection of primary CD4+ T cells. Overall, the data presented shows that HIV-1 generates circRNAs which promote viral replication by sequestering and inhibiting the functions of miR-6727-3p and miR-4722-3p.https://doi.org/10.1038/s44298-025-00105-0 |
| spellingShingle | Christopher Mauer Sean Paz Massimo Caputi Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication npj Viruses |
| title | Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication |
| title_full | Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication |
| title_fullStr | Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication |
| title_full_unstemmed | Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication |
| title_short | Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication |
| title_sort | backsplicing of the hiv 1 transcript generates multiple circrnas to promote viral replication |
| url | https://doi.org/10.1038/s44298-025-00105-0 |
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