Alpha-helicoidal HEAT-like Repeat Proteins (alphaRep) Selected as Interactors of HIV-1 Nucleocapsid Negatively Interfere with Viral Genome Packaging and Virus Maturation

Abstract : A new generation of artificial proteins, derived from alpha-helicoidal HEAT-like repeat protein scaffolds (alphaRep), was previously characterized as an effective source of intracellular interfering proteins. In this work, a phage-displayed library of alphaRep 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 alphaRep binders were isolated from the screen, alphaRep4E3 (32 kDa; 7 internal repeats) and alphaRep9A8 (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 alphaRep4E3 and alphaRep9A8 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: alphaRep4E3 blocked the viral genome packaging, whereas alphaRep9A8 altered both virus maturation and genome packaging. Interestingly, SupT1 cells stably expressing alphaRep9A8 acquired long-term resistance to HIV-1, implying that alphaRep proteins can act as antiviral restriction-like factors.
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https://hal-univ-lyon1.archives-ouvertes.fr/hal-02191904
Contributor : Marie-Gabrielle Chautard <>
Submitted on : Tuesday, July 23, 2019 - 4:57:58 PM
Last modification on : Tuesday, September 24, 2019 - 4:23:47 PM

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S. Hadpech, S. Nangola, K. Chupradit, K. Fanhchaksai, W. Furnon, et al.. Alpha-helicoidal HEAT-like Repeat Proteins (alphaRep) Selected as Interactors of HIV-1 Nucleocapsid Negatively Interfere with Viral Genome Packaging and Virus Maturation. Scientific Reports, 2017, 7 (1), pp.16335. ⟨10.1038/s41598-017-16451-w⟩. ⟨hal-02191904⟩

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