LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends
Processing of unintegrated linear HIV-1 cDNA by the host DNA repair system results in its degradation and/or circularization. As a consequence, deficient viral cDNA integration generally leads to an increase in the levels of HIV-1 cDNA circles containing one or two long terminal repeats (LTRs). Intr...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/9/9/259 |
| _version_ | 1818033318502858752 |
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| author | Murilo T. D. Bueno Daniel Reyes Manuel Llano |
| author_facet | Murilo T. D. Bueno Daniel Reyes Manuel Llano |
| author_sort | Murilo T. D. Bueno |
| collection | DOAJ |
| description | Processing of unintegrated linear HIV-1 cDNA by the host DNA repair system results in its degradation and/or circularization. As a consequence, deficient viral cDNA integration generally leads to an increase in the levels of HIV-1 cDNA circles containing one or two long terminal repeats (LTRs). Intriguingly, impaired HIV-1 integration in LEDGF/p75-deficient cells does not result in a correspondent increase in viral cDNA circles. We postulate that increased degradation of unintegrated linear viral cDNA in cells lacking the lens epithelium-derived growth factor (LEDGF/p75) account for this inconsistency. To evaluate this hypothesis, we characterized the nucleotide sequence spanning 2-LTR junctions isolated from LEDGF/p75-deficient and control cells. LEDGF/p75 deficiency resulted in a significant increase in the frequency of 2-LTRs harboring large deletions. Of note, these deletions were dependent on the 3′ processing activity of integrase and were not originated by aberrant reverse transcription. Our findings suggest a novel role of LEDGF/p75 in protecting the unintegrated 3′ processed linear HIV-1 cDNA from exonucleolytic degradation. |
| first_indexed | 2024-12-10T06:21:22Z |
| format | Article |
| id | doaj.art-d4ffe7fbd00441c293188789c968b17e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-10T06:21:22Z |
| publishDate | 2017-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-d4ffe7fbd00441c293188789c968b17e2022-12-22T01:59:20ZengMDPI AGViruses1999-49152017-09-019925910.3390/v9090259v9090259LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA EndsMurilo T. D. Bueno0Daniel Reyes1Manuel Llano2Department of Biological Sciences, University of Texas at El Paso. El Paso, TX 79968, USADepartment of Biological Sciences, University of Texas at El Paso. El Paso, TX 79968, USADepartment of Biological Sciences, University of Texas at El Paso. El Paso, TX 79968, USAProcessing of unintegrated linear HIV-1 cDNA by the host DNA repair system results in its degradation and/or circularization. As a consequence, deficient viral cDNA integration generally leads to an increase in the levels of HIV-1 cDNA circles containing one or two long terminal repeats (LTRs). Intriguingly, impaired HIV-1 integration in LEDGF/p75-deficient cells does not result in a correspondent increase in viral cDNA circles. We postulate that increased degradation of unintegrated linear viral cDNA in cells lacking the lens epithelium-derived growth factor (LEDGF/p75) account for this inconsistency. To evaluate this hypothesis, we characterized the nucleotide sequence spanning 2-LTR junctions isolated from LEDGF/p75-deficient and control cells. LEDGF/p75 deficiency resulted in a significant increase in the frequency of 2-LTRs harboring large deletions. Of note, these deletions were dependent on the 3′ processing activity of integrase and were not originated by aberrant reverse transcription. Our findings suggest a novel role of LEDGF/p75 in protecting the unintegrated 3′ processed linear HIV-1 cDNA from exonucleolytic degradation.https://www.mdpi.com/1999-4915/9/9/259LEDGF/p75HIV-12-LTR circlesunintegrated HIV-1 cDNA |
| spellingShingle | Murilo T. D. Bueno Daniel Reyes Manuel Llano LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends Viruses LEDGF/p75 HIV-1 2-LTR circles unintegrated HIV-1 cDNA |
| title | LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends |
| title_full | LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends |
| title_fullStr | LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends |
| title_full_unstemmed | LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends |
| title_short | LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends |
| title_sort | ledgf p75 deficiency increases deletions at the hiv 1 cdna ends |
| topic | LEDGF/p75 HIV-1 2-LTR circles unintegrated HIV-1 cDNA |
| url | https://www.mdpi.com/1999-4915/9/9/259 |
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