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Related Concept Videos

DNA Packaging00:58

DNA Packaging

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Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
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HIV-1 Packaging Visualised by In-Gel SHAPE.

Aaron R D'Souza1,2, Dhivya Jayaraman1, Ziqi Long3

  • 1Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.

Viruses
|December 28, 2021
PubMed
Summary
This summary is machine-generated.

Human immunodeficiency virus type 1 (HIV-1) uses its Gag protein to package two copies of its genomic RNA (gRNA) into new virions. This study reveals how Gag protein interactions initiate RNA packaging by inducing structural changes necessary for genome stabilization.

Keywords:
GagHIV-1NCRNA structuredimerisationin-gel SHAPEpackaging

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Area of Science:

  • Molecular virology
  • Structural biology
  • Biochemistry

Background:

  • Human immunodeficiency virus type 1 (HIV-1) requires packaging of two genomic RNA (gRNA) copies into virions for infectivity.
  • The viral structural protein Gag mediates this gRNA packaging process.
  • The exact mechanism and structural dynamics of HIV-1 gRNA packaging remain poorly understood due to limitations in studying RNA structure within dynamic RNA-protein complexes.

Purpose of the Study:

  • To investigate the initial structural changes of the HIV-1 packaging signal RNA upon interaction with the Gag polyprotein.
  • To elucidate the role of the Gag protein, specifically its NC domain, in inducing RNA conformational changes essential for gRNA packaging.
  • To compare the RNA structural dynamics induced by the full Gag polyprotein versus the NC domain alone.

Main Methods:

  • Application of the in-gel SHAPE (selective 2'OH acylation analysed by primer extension) technique.
  • Analysis of RNA structural changes in the HIV-1 packaging signal RNA.
  • Comparative study of RNA-protein interactions involving the Gag polyprotein and its NC domain.

Main Results:

  • Gag protein interactions with monomeric packaging signal RNA induce a conformational switch towards a dimerisation-competent structure.
  • The Gag-RNA complex stabilizes the RNA dimer structure.
  • The NC domain of Gag plays a crucial role in initiating these RNA structural rearrangements.

Conclusions:

  • HIV-1 Gag protein initiates gRNA packaging by inducing specific structural changes in the packaging signal RNA.
  • These Gag-mediated structural transitions facilitate RNA dimerization and stabilize the complex, essential for efficient viral genome packaging.
  • The findings offer novel insights into the regulation of HIV-1 genome translation and packaging.