| Long-range recombination gradient between HIV-1 subtypes B and C variants caused by sequence differences in the dimerization initiation signal region. | |
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MedLine Citation:
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PMID: 18314135 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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HIV-1 intersubtype recombinants have an increasingly important role in shaping the AIDS pandemic. We sought to understand the molecular mechanisms that generate intersubtype HIV-1 recombinants. We analyzed recombinants of HIV-1 subtypes B and C, and identified their crossover junctions in the viral genome from the 5' long terminal repeat (LTR) to the end of pol. We identified 56 recombination events in 56 proviruses; the distribution of these events indicated an apparent recombination gradient: there were significantly more crossover junctions in the 3' half than in the 5' half of the region analyzed. HIV-1 subtypes B and C have different dimerization initiation signal (DIS). We hypothesized that the inability of subtype B and C RNAs to form perfect base-pairing of the DIS affects the dimeric RNA structure and causes a decrease in recombination events at the 5' end of the viral genome. To test this hypothesis, we examined recombinants generated from a subtype C virus and a modified subtype B virus containing a subtype C DIS. In the 56 proviruses analyzed, we identified 96 recombination events, which are significantly more frequent than in the B/C recombinants. Furthermore, these crossover junctions were distributed evenly throughout the region analyzed, indicating that the recombination gradient was corrected by matching the DIS. Therefore, base-pairing at the DIS has an important function during HIV-1 reverse transcription, most likely in maintaining nucleic-acid structure in the complex. These findings reveal elements important to retroviral recombination and provide insights into the generation of HIV-1 intersubtype recombinants that are important to the AIDS epidemic. |
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Authors:
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Mario P S Chin; Sook-Kyung Lee; Jianbo Chen; Olga A Nikolaitchik; Douglas A Powell; Mathew J Fivash; Wei-Shau Hu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2008-02-09 |
Journal Detail:
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Title: Journal of molecular biology Volume: 377 ISSN: 1089-8638 ISO Abbreviation: J. Mol. Biol. Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-03-24 Completed Date: 2008-07-01 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2985088R Medline TA: J Mol Biol Country: England |
Other Details:
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Languages: eng Pagination: 1324-33 Citation Subset: IM |
Affiliation:
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HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Base Pairing
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genetics Base Sequence Dimerization Genome, Viral* HIV-1 / genetics*, metabolism Humans Nucleic Acid Conformation RNA, Viral / chemistry, genetics Recombination, Genetic / genetics* Viral Proteins / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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Z01 BC010504-05/BC/NCI NIH HHS; Z01 BC010814-01/BC/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Viral; 0/Viral Proteins |
| Comments/Corrections | |
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