A proposal for a new HIV-1 DLS structural model.

Nucleic Acids Research
Jun-Ichi SakuragiHironori Sato

Abstract

The dimer initiation site/dimer linkage sequence (DIS/DLS) region of the human immunodeficiency virus type 1 (HIV-1) RNA genome is suggested to play essential roles at various stages of the viral life cycle. Through a novel assay we had recently developed, we reported on the necessary and sufficient region for RNA dimerization in the HIV-1 virion. Using this system, we performed further detailed mapping of the functional base pairs necessary for HIV-1 DLS structure. Interestingly, the study revealed a previously unnoticed stem formation between two distantly positioned regions. Based on this and other findings on functional base pairing in vivo, we propose new 3D models of the HIV-1 DLS which contain a unique pseudoknot-like conformation. Since this pseudoknot-like conformation appears to be thermodynamically stable, forms a foundational skeleton for the DLS and sterically restricts the spontaneous diversification of DLS conformations, its unique shape may contribute to the viral life cycle and potentially serve as a novel target for anti-HIV-1 therapies.

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Citations

Dec 18, 2013·Journal of Virology·Nikki van BelBen Berkhout
Jul 6, 2014·Nature Communications·Ekram W Abd El-WahabRoland Marquet
Aug 29, 2013·Reviews in Medical Virology·Cristina Romero-López, Alfredo Berzal-Herranz
May 20, 2015·Virology·Nikki van BelBen Berkhout
Jul 24, 2012·Virus Research·José A Reyes-DariasAlfredo Berzal-Herranz
Mar 29, 2013·RNA Biology·Stefanie A Knoepfel, Ben Berkhout
Feb 25, 2014·Journal of Biomolecular Structure & Dynamics·Irina N KolomietsDmytro M Hovorun
Aug 19, 2016·Computational and Structural Biotechnology Journal·Ying HuangFeilong Deng
Nov 12, 2016·Retrovirology·Sayuri SakuragiJun-Ichi Sakuragi
Nov 15, 2016·RNA Biology·Serena BernacchiJean-Christophe Paillart
Jan 26, 2018·Retrovirology·Dhivya Jayaraman, Julia Claire Kenyon
Apr 7, 2018·Frontiers in Microbiology·Noé DuboisSerena Bernacchi

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Methods Mentioned

BETA
NMR
transfection
ELISA
electrophoresis
chemical modification

Software Mentioned

CentroidFold
Fold
AMBER9
Sym
MC

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