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Cited by 51HIV Research and Treatmentthermodynamics and calorimetric analysesHIV/AIDS drug development and treatment

The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV

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Tanwar, Hanumant S., Khoo, Keith K., Garvey, Megan, Waddington, Lynne, Leis, Andrew, Hijnen, Marcel, Velkov, Tony, Dumsday, Geoff J. +2 more·2017·PLOS Pathogens
DOI 10.1371/journal.ppat.1006221PMC PMC5336307
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Abstract

The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packaging are essential elements that facilitate HIV assembly. However, mechanistic details of these interactions are not clearly defined. Here, we overcome previous limitations in producing large quantities of full-length recombinant Pr55Gag that is required for isothermal titration calorimetry (ITC) studies, and we have revealed the thermodynamic properties of HIV assembly for the first time. Thermodynamic analysis showed that the binding between RNA and HIV Pr55Gag is an energetically favourable reaction (ΔG<0) that is further enhanced by the oligomerization of Pr55Gag. The change in enthalpy (ΔH) widens sequentially from: (1) Pr55Gag-Psi RNA binding during HIV genome selection; to (2) Pr55Gag-Guanosine Uridine (GU)-containing RNA binding in cytoplasm/plasma membrane; and then to (3) Pr55Gag-Adenosine(A)-containing RNA binding in immature HIV. These data imply the stepwise increments of heat being released during HIV biogenesis may help to facilitate the process of viral assembly. By mimicking the interactions between A-containing RNA and oligomeric Pr55Gag in immature HIV, it was noted that a p6 domain truncated Pr50Gag Δp6 is less efficient than full-length Pr55Gag in this thermodynamic process. These data suggest a potential unknown role of p6 in Pr55Gag-Pr55Gag oligomerization and/or Pr55Gag-RNA interaction during HIV assembly. Our data provide direct evidence on how nucleic acid sequences and the oligomeric state of Pr55Gag regulate HIV assembly.

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  • For efficient CA-CA interactions, gRNA binding to CA is necessary so that I-domains within CA can be readily exposed.

    “for efficient CA–CA interactions, gRNA binding to CA is necessary so that I-domains within CA can be readily exposed”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Tanwar et al. 2017

    The Introduction (page unavailable) says the nucleocapsid domain is responsible for genomic RNA packaging, while CA mediates Gag–Gag oligomerization. The Results on Pr55Gag–RNA binding report that RNA interaction and CA-mediated oligomerization are energetically linked, but do not show that genomic RNA must bind directly to CA or that such binding exposes CA I-domains. (LLM, conf=0.86)

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Authors
Tanwar, H. S., Khoo, K. K., Garvey, M., Waddington, L., Leis, A., Hijnen, M., Velkov, T., Dumsday, G. J., McKinstry, W. J., & Mak, J.
Affiliations
  • Commonwealth Scientific and Industrial Research Organisation (AU)
  • Monash University (AU)
  • CSIRO Manufacturing (AU)
Corresponding author
Mak, Johnson
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2017-02-21
Volume
13
Issue
2
Pages
e1006221
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1006221
PMC
PMC5336307
OpenAlex
W2590258378
Cited by
51
References
2
Citations by year
2026: 3 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 10 · 2020: 8 · 2019: 4 · 2018: 12 · 2017: 1
FWCI
3.72
Type
journal article
Language
en
Update notices
new_version (2017-03-03)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Monash University Research Portal (Monash University) (submittedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Griffith Research Online (submittedVersion, cc-by)
Funders
  • National Health and Medical Research Council (543107, 1121697)
  • National Institute of General Medical Sciences (NIH RO1 GM064347)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › thermodynamics and calorimetric analyses
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
HIV-1 assembly, Pr55gag, RNA packaging, oligomerization, binding thermodynamics, nucleic acid binding
MeSH terms
Amino Acid Sequence, Base Sequence, Calorimetry, Chromatography, Microscopy, Electron, Protein Precursors, RNA, Viral, Thermodynamics, Blotting, Western, HIV-1, Virus Assembly, Immunoprecipitation

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