Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1maturation inhibitor bevirimat
In: Retrovirology, Jg. 7 (2010-04-01), Heft 1
Online
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Zugriff:
Background The maturation inhibitor bevirimat (BVM) potently inhibits human immunodeficiency virus type 1 (HIV-1) replication by blocking capsid-spacer peptide 1 (CA-SP1) cleavage. Recent clinical trials demonstrated that a significant proportion of HIV-1-infected patients do not respond to BVM. A patient's failure to respond correlated with baseline polymorphisms at SP1 residues 6-8. Results In this study, we demonstrate that varying levels of BVM resistance are associated with point mutations at these residues. BVM susceptibility was maintained by SP1-Q6A, -Q6H and -T8A mutations. However, an SP1-V7A mutation conferred high-level BVM resistance, and SP1-V7M and T8Δ mutations conferred intermediate levels of BVM resistance. Conclusions Future exploitation of the CA-SP1 cleavage site as an antiretroviral drug target will need to overcome the baseline variability in the SP1 region of Gag.
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Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1maturation inhibitor bevirimat
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Autor/in / Beteiligte Person: | Adamson, Catherine S. ; Sakalian, Michael ; Salzwedel, Karl ; Freed, Eric O. ; University of St Andrews. School of Medicine ; University of St Andrews. Biomedical Sciences Research Complex |
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Zeitschrift: | Retrovirology, Jg. 7 (2010-04-01), Heft 1 |
Veröffentlichung: | BMC, 2010 |
Medientyp: | unknown |
ISSN: | 1742-4690 (print) |
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