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4th International AIDS Society Conference on HIV Pathogenesis and TreatmentSydney, Australia - July 22 - 25, 2007 |
LONG-RANGE RECOMBINATION GRADIENT IN INTERSUBTYPE HIV-1 RECOMBINATION
IAS Conf HIV Pathog Treat 2007 Jul 22-25;4th: Abstract No. MOAA203
Chin M.P.S.1, Lee S.-K.1, Chen J.1, Nikolaitchik O.A.1, Powell D.2, Fivash Jr. M.J.2, Hu W.-S.1
1HIV Drug Resistance Program, National Cancer Institute, Frederick, United States, 2Data Management Services, National Cancer Institute, Frederick, United States
OBJECTIVE: HIV-1 intersubtype recombinants have an increasing role in shaping the AIDS pandemic. We sought to understand the molecular mechanisms of how these recombinants are generated and the barriers to recombination.
METHODS: Two near full-length HIV-1 vectors, one subtype B and one subtype C, were used to study recombination in the viral sequences. Each vector contains a nonfunctional green fluorescent protein (GFP) gene inactivated by different mutations; recombination between the mutations allows reconstitution of a wildtype GFP. We isolated single GFP+ cell clones and sequenced a 5-kb region (5’LTR to the end of pol) of the proviruses to identify recombination events.
RESULTS: We have sequenced ~290 kb of proviral sequences (from 56 GFP+ cell clones) and identified 56 recombination events between subtype B and C viruses. We observed significantly more recombination events in the 3’ half of the sequence than 5’ half of the sequences (p=0.002). Subtype B and C HIV-1 have different dimerization initiation signal (DIS). We hypothesized that the inability of subtype B and C RNAs to form perfect basepairing of DIS affects the dimeric RNA structure and caused decreased 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 subtype C DIS. In 56 recombinants, we identified 96 recombination events, which is significantly higher than the B/C recombinants (p=0.003). Furthermore, these recombination events were distributed evenly throughout the 5-kb region, indicating the recombination gradient was corrected by matching the DIS.
CONCLUSIONS: The DIS sequence in HIV-1 not only plays a role in RNA dimerization but also serves an important function in maintaining dimeric RNA structure important for recombination. Difference in DIS sequence presents a barrier to certain intersubtype HIV-1 recombination.
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2007-07-22
MOAA203
HIV Diversity, Tropism and Compartmentalization
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