Journal
VIROLOGY
Volume 479, Issue -, Pages 403-417Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2015.03.021
Keywords
Retrovirus; Aspartic protease; Maturation; Human immunodeficiency virus; Gag; Protease inhibitor; Antiretroviral therapy; Resistance; Virus structure
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Funding
- Grant Agency of the Czech Republic [P208-12-G016]
- Ministry of Education of the Czech Republic [LO1302]
- Deutsche Forschungsgemeinschaft [Kr906/7-1, MU885/5-1]
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Proteolytic processing of viral polyproteins is essential for retrovirus infectivity. Retroviral proteases (PR) become activated during or after assembly of the immature, non-infectious virion. They cleave viral polyproteins at specific sites, inducing major structural rearrangements termed maturation. Maturation converts retroviral enzymes into their functional form, transforms the immature shell into a metastable state primed for early replication events, and enhances viral entry competence. Not only cleavage at all PR recognition sites, but also an ordered sequence of cleavages is crucial. Proteolysis is tightly regulated, but the triggering mechanisms and kinetics and pathway of morphological transitions remain enigmatic. Here, we outline PR structures and substrate specificities focusing on HIV PR as a therapeutic target. We discuss design and clinical success of HIV PR inhibitors, as well as resistance development towards these drugs. Finally, we summarize data elucidating the role of proteolysis in maturation and highlight unsolved questions regarding retroviral maturation. (C) 2015 Elsevier Inc. All rights reserved.
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