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Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity
BACKGROUND: APOBEC3 (A3) proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and to transposition of endogenous retroelements. A3A has significant homology to the C-terminus of A3G but has only a single cytidine deaminase active site (C...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2018723/ https://www.ncbi.nlm.nih.gov/pubmed/17727729 http://dx.doi.org/10.1186/1742-4690-4-61 |
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author | Goila-Gaur, Ritu Khan, Mohammad A Miyagi, Eri Kao, Sandra Strebel, Klaus |
author_facet | Goila-Gaur, Ritu Khan, Mohammad A Miyagi, Eri Kao, Sandra Strebel, Klaus |
author_sort | Goila-Gaur, Ritu |
collection | PubMed |
description | BACKGROUND: APOBEC3 (A3) proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and to transposition of endogenous retroelements. A3A has significant homology to the C-terminus of A3G but has only a single cytidine deaminase active site (CDA), unlike A3G, which has a second N-terminal CDA previously found to be important for Vif sensitivity and virus encapsidation. A3A is packaged into HIV-1 virions but, unlike A3G, does not have antiviral properties. Here, we investigated the reason for the lack of A3A antiviral activity. RESULTS: Sequence alignment of A3G and A3A revealed significant homology of A3A to the C-terminal region of A3G. However, while A3G co-purified with detergent-resistant viral nucleoprotein complexes (NPC), virus-associated A3A was highly detergent-sensitive leading us to speculate that the ability to assemble into NPC may be a property conveyed by the A3G N-terminus. To test this model, we constructed an A3G-3A chimeric protein, in which the N-terminal half of A3G was fused to A3A. Interestingly, the A3G-3A chimera was packaged into HIV-1 particles and, unlike A3A, associated with the viral NPC. Furthermore, the A3G-3A chimera displayed strong antiviral activity against HIV-1 and was sensitive to inhibition by HIV-1 Vif. CONCLUSION: Our results suggest that the A3G N-terminal domain carries determinants important for targeting the protein to viral NPCs. Transfer of this domain to A3A results in A3A targeting to viral NPCs and confers antiviral activity. |
format | Text |
id | pubmed-2018723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-20187232007-10-12 Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity Goila-Gaur, Ritu Khan, Mohammad A Miyagi, Eri Kao, Sandra Strebel, Klaus Retrovirology Research BACKGROUND: APOBEC3 (A3) proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and to transposition of endogenous retroelements. A3A has significant homology to the C-terminus of A3G but has only a single cytidine deaminase active site (CDA), unlike A3G, which has a second N-terminal CDA previously found to be important for Vif sensitivity and virus encapsidation. A3A is packaged into HIV-1 virions but, unlike A3G, does not have antiviral properties. Here, we investigated the reason for the lack of A3A antiviral activity. RESULTS: Sequence alignment of A3G and A3A revealed significant homology of A3A to the C-terminal region of A3G. However, while A3G co-purified with detergent-resistant viral nucleoprotein complexes (NPC), virus-associated A3A was highly detergent-sensitive leading us to speculate that the ability to assemble into NPC may be a property conveyed by the A3G N-terminus. To test this model, we constructed an A3G-3A chimeric protein, in which the N-terminal half of A3G was fused to A3A. Interestingly, the A3G-3A chimera was packaged into HIV-1 particles and, unlike A3A, associated with the viral NPC. Furthermore, the A3G-3A chimera displayed strong antiviral activity against HIV-1 and was sensitive to inhibition by HIV-1 Vif. CONCLUSION: Our results suggest that the A3G N-terminal domain carries determinants important for targeting the protein to viral NPCs. Transfer of this domain to A3A results in A3A targeting to viral NPCs and confers antiviral activity. BioMed Central 2007-08-29 /pmc/articles/PMC2018723/ /pubmed/17727729 http://dx.doi.org/10.1186/1742-4690-4-61 Text en Copyright © 2007 Goila-Gaur et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Goila-Gaur, Ritu Khan, Mohammad A Miyagi, Eri Kao, Sandra Strebel, Klaus Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity |
title | Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity |
title_full | Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity |
title_fullStr | Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity |
title_full_unstemmed | Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity |
title_short | Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity |
title_sort | targeting apobec3a to the viral nucleoprotein complex confers antiviral activity |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2018723/ https://www.ncbi.nlm.nih.gov/pubmed/17727729 http://dx.doi.org/10.1186/1742-4690-4-61 |
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