HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat

0370143 - ÚOCHB 2012 RIV GB eng J - Journal Article
Fun, A. - Maarseveen van, N. M. - Pokorná, Jana - Maas, R. E. - Schipper, P. J. - Konvalinka, Jan - Nijhuis, M.
HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat.
Retrovirology. Roč. 8, č. 70 (2011), s. 1-12. E-ISSN 1742-4690
Grant - others:European Union(XE) LWSHP-CT-2007-037693
Institutional research plan: CEZ:AV0Z40550506
Keywords : immunodeficiency-virus type-1 * gag spacer peptide-1 * replication capacity * compensatory mutations * cleavage sites
Subject RIV: CE - Biochemistry
Impact factor: 6.470, year: 2011

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.
Permanent Link: http://hdl.handle.net/11104/0204028