Abstract

A new generation of artificial proteins, derived from alpha-helicoidal HEAT-like repeat protein scaffolds (αRep), was previously characterized as an effective source of intracellular interfering proteins. In this work, a phage-displayed library of αRep was screened on a region of HIV-1 Gag polyprotein encompassing the C-terminal domain of the capsid, the SP1 linker and the nucleocapsid. This region is known to be essential for the late steps of HIV-1 life cycle, Gag oligomerization, viral genome packaging and the last cleavage step of Gag, leading to mature, infectious virions. Two strong αRep binders were isolated from the screen, αRep4E3 (32 kDa; 7 internal repeats) and αRep9A8 (28 kDa; 6 internal repeats). Their antiviral activity against HIV-1 was evaluated in VLP-producer cells and in human SupT1 cells challenged with HIV-1. Both αRep4E3 and αRep9A8 showed a modest but significant antiviral effects in all bioassays and cell systems tested. They did not prevent the proviral integration reaction, but negatively interfered with late steps of the HIV-1 life cycle: αRep4E3 blocked the viral genome packaging, whereas αRep9A8 altered both virus maturation and genome packaging. Interestingly, SupT1 cells stably expressing αRep9A8 acquired long-term resistance to HIV-1, implying that αRep proteins can act as antiviral restriction-like factors.

Details

Title
Alpha-helicoidal HEAT-like Repeat Proteins (αRep) Selected as Interactors of HIV-1 Nucleocapsid Negatively Interfere with Viral Genome Packaging and Virus Maturation
Author
Hadpech, Sudarat 1 ; Nangola, Sawitree 2 ; Chupradit, Koollawat 3 ; Kanda Fanhchaksai 3 ; Furnon, Wilhelm 4 ; Urvoas, Agathe 5 ; Valerio-Lepiniec, Marie 5 ; Minard, Philippe 5 ; Boulanger, Pierre 4 ; Saw-See, Hong 6 ; Tayapiwatana, Chatchai 3 

 Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Faculty of Pharmaceutical Science, Burapha University, Muang District, Chonburi Province, Thailand; University Lyon 1, UMR754-INRA-EPHE, Viral Infections and Comparative Pathology, 50, Avenue Tony Garnier, Lyon Cedex 07, France 
 Division of Clinical Immunology and Transfusion Sciences, School of Allied Health Sciences, University of Phayao, Phayao, Thailand 
 Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand 
 University Lyon 1, UMR754-INRA-EPHE, Viral Infections and Comparative Pathology, 50, Avenue Tony Garnier, Lyon Cedex 07, France 
 Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette cedex, France 
 University Lyon 1, UMR754-INRA-EPHE, Viral Infections and Comparative Pathology, 50, Avenue Tony Garnier, Lyon Cedex 07, France; Institut National de la Santé et de la Recherche Médicale, 101, rue de Tolbiac, Paris Cedex 13, France 
Pages
1-19
Publication year
2017
Publication date
Nov 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1968994154
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.