Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Retrovirology cung cấp cho các bạn kiến thức về ngành y đề tài: Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1maturation inhibitor bevirimat. | Adamson et al. Retrovirology 2010 7 36 http content 7 1 36 gtr RETROVIROLOGY RESEARCH Open Access Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- Imaturation inhibitor bevirimat Catherine S Adamson 1 3 Michael Sakalian2 Karl Salzwedel2 and Eric O Freed1 Abstract 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 T8A 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. Background Human immunodeficiency virus type 1 HIV-1 infectivity is dependent on virion maturation a morphological rearrangement of the viral core that occurs concomitant with virus particle release 1 2 . HIV-1 maturation is triggered by cleavage of the Gag polyprotein catalyzed by the viral protease PR into the matrix MA capsid CA spacer peptide 1 SP1 nucleocapsid NC spacer peptide SP2 and p6 constituents. Gag cleavage occurs as a sequential cascade of steps that is kinetically controlled by the differential rate of processing at each of the five cleavage sites in Gag 3-9 . First Gag is cleaved into two fragments MA-CA-SP1 and NC-SP2-p6. Next the MA and p6 domains are released and finally the CA and NC domains are liberated from the remaining CA-SP1 and NC-SP2 processing .
