tailieunhanh - Báo cáo y học: " The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid | Retrovirology Research The sequence of the CA-SPI junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O- 3 3 -dimethylsuccinyl -betulinic acid Jing Zhou1 Chin Ho Chen2 and Christopher Aiken 1 Address Department of Microbiology and Immunology Vanderbilt University School of Medicine Nashville TN USA and 2Department of Pathology Duke University Medical Center Durham NC USA Email Jing Zhou - Chin Ho Chen - chc@ Christopher Aiken - Corresponding author Published 29 June 2004 Received 09 June 2004 Retrovirology 2004 1 15 doi 1742-4690-1-15 Accepted 29 June 2004 This article is available from http content 1 1 15 2004 Zhou et al licensee BioMed Central Ltd. This is an Open Access article verbatim copying and redistribution of this article are permitted in all media for any purpose provided this notice is preserved along with the article s original URL. Abstract Background Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-0- 3 3 -dimethylsuccinyl -betulinic acid DSB specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4 T cells. Results Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to .