HIV-1 RNA Packaging Mechanisms and Viral Assembly

Human immunodeficiency virus type 1 (HIV-1) relies on a finely tuned interplay between its genomic RNA and the viral structural polyprotein Gag to ensure production of infectious particles. Upon synthesis in the cytosol, unspliced HIV-1 RNA adopts distinct conformations within its highly structured 5′ untranslated region, including a cis-acting packaging signal (Ψ) that is selectively recognised by the nucleocapsid domain of Gag. Two copies of genomic RNA dimerise via specific stem-loop interactions, establishing a dimeric genome that is preferentially encapsidated at the plasma membrane. Gag initially binds RNA as monomers or low-order multimers in the cytoplasm, then multimerises into higher-order assemblies only upon membrane association, driving budding and release of virions. Packaging must discriminate against abundant cellular and spliced viral RNAs, a process governed both by the primary sequence of Ψ and by its three-dimensional architecture. In addition, certain host non-coding RNAs are selectively co-packaged and may contribute to particle stability or trafficking. The spatial regulation of translation, the timing of Gag–RNA encounter and the recruitment of host endosomal sorting complexes required for transport (ESCRT) collectively define the efficiency and fidelity of HIV-1 assembly. A deeper understanding of these steps is critical for therapeutic intervention and for the design of antiviral agents that disrupt genome selection or particle formation.

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HIV-1 RNA Packaging Mechanisms and Viral Assembly publication trend

The graph below shows the total number of articles in hiv-1 rna packaging mechanisms and viral assembly across all publications each year (not limited to Nature Index journals).

Technical terms

Gag polyprotein: The precursor structural protein that mediates both RNA binding and virion assembly.

Packaging signal (Ψ): A conserved RNA element within the 5′ UTR essential for selective encapsidation of the viral genome.

Unspliced genomic RNA: The full-length RNA transcript that functions both as mRNA for Gag and as the packaged viral genome.

RNA dimerization: The non-covalent pairing of two genomic RNA molecules via specific stem-loop motifs, required for efficient encapsidation.

Virion: A complete, extracellular virus particle comprising a lipid envelope, Gag shell and packaged genomic RNA.

References

1. Translation of unspliced retroviral genomic RNA in the host cell is regulated in both space and time. Journal of Cell Biology (2025).
2. HIV-1 RNA genome packaging: it’s G-rated. mBio (2024).
3. High-Throughput SHAPE Analysis Reveals Structures in HIV-1 Genomic RNA Strongly Conserved across Distinct Biological States. PLOS Biology (2008).
4. Dimeric RNA Recognition Regulates HIV-1 Genome Packaging. PLOS Pathogens (2013).
5. Dissection of specific binding of HIV-1 Gag to the 'packaging signal' in viral RNA. eLife (2017).
6. The Host RNAs in Retroviral Particles. Viruses (2016).
7. Analysis of the Initiating Events in HIV-1 Particle Assembly and Genome Packaging. PLOS Pathogens (2010).
8. Dynamics of HIV-1 Assembly and Release. PLOS Pathogens (2009).