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Multiple, Switchable Protein:RNA Interactions Regulate Human Immunodeficiency Virus Type 1 Assembly.

Paul Bieniasz¹, Alice Telesnitsky²

¹Laboratory of Retrovirology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA;

Annual Review of Virology

|July 27, 2018

Summary

Human immunodeficiency virus type 1 (HIV-1) particle assembly involves complex protein-RNA interactions. These interactions change dynamically during virion formation, influencing assembly and maturation.

Keywords:

Gag HIV-1 RNA assembly packaging

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Area of Science:

Virology
Molecular Biology
Structural Biology

Background:

HIV-1 particle assembly is a complex process involving numerous protein-RNA interactions.
These interactions range from specific recognition of conserved RNA elements to less specific binding of variable sequences.
Understanding these interactions is crucial for comprehending viral replication and developing antiviral strategies.

Purpose of the Study:

To elucidate the dynamic nature of protein-RNA interactions during HIV-1 assembly.
To investigate how changes in RNA binding specificity contribute to virion morphogenesis.
To explore the role of the 5' leader RNA element and tRNA in regulating HIV-1 assembly initiation.

Main Methods:

Genetic studies to identify key viral components and their interactions.
Biochemical assays to characterize protein-RNA binding affinities and specificities.
Biophysical techniques to study conformational changes in RNA and proteins.
Structural biology approaches to visualize molecular complexes.

Main Results:

The 5' leader RNA element plays a critical role in initiating Gag recognition and can adopt variable conformations.
Gag protein's RNA binding specificity transiently shifts during multimerization, allowing recognition of the A-rich viral genome.
Transfer RNA (tRNA) may regulate assembly initiation by occluding Gag's membrane binding surface.
RNA interactions with viral enzymes are implicated in activating and ensuring accurate virion maturation.

Conclusions:

HIV-1 particle assembly is orchestrated by dynamic and context-dependent protein-RNA interactions.
Changes in RNA binding specificity are integral to successful virion morphogenesis and maturation.
Further research into these interactions could reveal novel therapeutic targets for HIV-1 infection.