Alpha-helicoidal HEAT-like repeat proteins (αRep) selected as interactors of HIV-1 nucleocapsid negatively interfere with viral genome packaging and virus maturation

Hadpech, S. et al. (2017) Alpha-helicoidal HEAT-like repeat proteins (αRep) selected as interactors of HIV-1 nucleocapsid negatively interfere with viral genome packaging and virus maturation. Scientific Reports, 7, 16335. (doi: 10.1038/s41598-017-16451-w) (PMID:29180782) (PMCID:PMC5703948)

[img] Text
235419.pdf - Published Version
Available under License Creative Commons Attribution.

3MB

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Furnon, Dr Wilhelm
Authors: Hadpech, S., Nangola, S., Chupradit, K., Fanhchaksai, K., Furnon, W., Urvoas, A., Valerio-Lepiniec, M., Minard, P., Boulanger, P., Hong, S.-S., and Tayapiwatana, C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Scientific Reports 7: 16335
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record