HIV-1 integrase binding to its cellular partners: A perspective from computational biology

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

doi:10.2174/13816128113199990631

HIV-1 integrase binding to its cellular partners: A perspective from computational biology

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^*

^*Corresponding author for this work

Cardiovascular Medicine & Sciences

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3412-3421
Number of pages	10
Journal	Current Pharmaceutical Design
Volume	20
Issue number	21
DOIs	https://doi.org/10.2174/13816128113199990631
Publication status	Published - 1 Jan 2014

Keywords

Class II mutant
HIV-1 integrase
Human Pin1
Protein-protein interaction

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2174/13816128113199990631

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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.",

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AU - Quy, Vo Cam

AU - Carnevale, Vincenzo

AU - Manganaro, Lara

AU - Lusic, Marina

AU - Rossetti, Giulia

AU - Leone, Vanessa

AU - Fenollar-Ferrer, Cristina

AU - Raugei, Simone

AU - Del Sal, Giannino

AU - Giacca, Mauro

AU - Carloni, Paolo

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N2 - 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.

AB - 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.

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KW - HIV-1 integrase

KW - Human Pin1

KW - Protein-protein interaction

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HIV-1 integrase binding to its cellular partners: A perspective from computational biology

Abstract

Keywords

UN SDGs

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