HIV-1 Integrase Binding to its Cellular Partners: A Perspective from Computational Biology

Author(s): Vo Cam Quy, Vincenzo Carnevale, Lara Manganaro, Marina Lusic, Giulia Rossetti, Vanessa Leone, Cristina Fenollar-Ferrer, Simone Raugei, Giannino Del Sal, Mauro Giacca, Paolo Carloni.

Journal Name: Current Pharmaceutical Design

Volume 20 , Issue 21 , 2014

Abstract:

Viral DNA integration into the infected cell genome is an essential step in the HIV-1 life cycle. Hence, the viral integrase enzyme has become an important target for antiviral therapy. The integrase's activity action relies on the binding to its cellular partners, therefore the knowledge of the structural determinants is very important from a therapeutic perspective. Here we first review published computer-aided structural predictions of HIV-1 integrase in complex with its interactors. These include DNA and the human HAT protein. Next, we present a prediction of the complex between HIV-1 integrase with the human prolyl-isomerase-1 (hPin1) enzyme. Interaction with hPin1 is crucial for efficient HIV-1 infection and it increases integrase stability (Manganaro et. al 2010, Nat. Med. 16, 329). The modeling presented here, which is validated against experimental data, provides a rationale for a variety of viral protein's mutations which impair protein function and HIV-1 virus replication in vivo without significantly affecting enzymatic activity.

Keywords: HIV-1 integrase, human Pin1, protein – protein interaction, class II mutant.

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Article Details

VOLUME: 20
ISSUE: 21
Year: 2014
Page: [3412 - 3421]
Pages: 10
DOI: 10.2174/13816128113199990631
Price: $58

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