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Human Immunodeficiency Virus gag and protease: partners in resistance

Title: Human Immunodeficiency Virus gag and protease: partners in resistance
Authors: Fun Axel; Wensing Annemarie MJ; Verheyen Jens; Nijhuis Monique
Source: Retrovirology, Vol 9, Iss 1, p 63 (2012)
Publisher Information: BMC
Publication Year: 2012
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: HIV; Particle maturation; Protease inhibitors; Maturation inhibitors; Gag mutations; Resistance; Cross-resistance; Immunologic diseases. Allergy; RC581-607
Description: Human Immunodeficiency Virus (HIV) maturation plays an essential role in the viral life cycle by enabling the generation of mature infectious virus particles through proteolytic processing of the viral Gag and GagPol precursor proteins. An impaired polyprotein processing results in the production of non-infectious virus particles. Consequently, particle maturation is an excellent drug target as exemplified by inhibitors specifically targeting the viral protease (protease inhibitors; PIs) and the experimental class of maturation inhibitors that target the precursor Gag and GagPol polyproteins. Considering the different target sites of the two drug classes, direct cross-resistance may seem unlikely. However, coevolution of protease and its substrate Gag during PI exposure has been observed both in vivo and in vitro . This review addresses in detail all mutations in Gag that are selected under PI pressure. We evaluate how polymorphisms and mutations in Gag affect PI therapy, an aspect of PI resistance that is currently not included in standard genotypic PI resistance testing. In addition, we consider the consequences of Gag mutations for the development and positioning of future maturation inhibitors.
Document Type: article in journal/newspaper
Language: English
Relation: http://www.retrovirology.com/content/9/1/63; https://doaj.org/toc/1742-4690; https://doaj.org/article/eb549ddaf0524afab3ea99df876b36d4
DOI: 10.1186/1742-4690-9-63
Availability: https://doi.org/10.1186/1742-4690-9-63; https://doaj.org/article/eb549ddaf0524afab3ea99df876b36d4
Accession Number: edsbas.DE10D09F
Database: BASE