tailieunhanh - Báo cáo y học: "HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat. | Fun et al. Retrovirology 2011 8 70 http content 8 1 70 RETR0VIR0L0GY RESEARCH Open Access HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat 1 12 1 12 Axel Fun Noortje M van Maarseveen Jana Pokorná Renée EM Maas Pauline J Schipper Jan Konvalinka and Monique Nijhuis1 Abstract Background Maturation inhibitors are an experimental class of antiretrovirals that inhibit Human Immunodeficiency Virus HIV particle maturation the structural rearrangement required to form infectious virus particles. This rearrangement is triggered by the ordered cleavage of the precursor Gag polyproteins into their functional counterparts by the viral enzyme protease. In contrast to protease inhibitors maturation inhibitors impede particle maturation by targeting the substrate of protease Gag instead of the protease enzyme itself. Direct cross-resistance between protease and maturation inhibitors may seem unlikely but the co-evolution of protease and its substrate Gag during protease inhibitor therapy could potentially affect future maturation inhibitor therapy. Previous studies showed that there might also be an effect of protease inhibitor resistance mutations on the development of maturation inhibitor resistance but the exact mechanism remains unclear. We used wild-type and protease inhibitor resistant viruses to determine the impact of protease inhibitor resistance mutations on the development of maturation inhibitor resistance. Results Our resistance selection studies demonstrated that the resistance profiles for the maturation inhibitor bevirimat are more diverse for viruses with a mutated protease compared to viruses with a wild-type protease. Viral replication did not appear to be a major factor during emergence of bevirimat resistance. In all in vitro selections one of four mutations was selected Gag V362I A364V S368N or V370A. The impact of these mutations on maturation inhibitor resistance and .