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Cited by 91HIV Research and TreatmentT-cell and Retrovirus StudiesHIV/AIDS drug development and treatment

How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle

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Lingappa, Jaisri R., Reed, Jonathan C., Tanaka, Motoko, Chutiraka, Kasana, Robinson, Bridget A.·2014·Virus Research
DOI 10.1016/j.virusres.2014.07.001PMC PMC4351045
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Abstract

During the late stage of the viral life cycle, HIV-1 Gag assembles into a spherical immature capsid, and undergoes budding, release, and maturation. Here we review events involved in immature capsid assembly from the perspective of five different approaches used to study this process: mutational analysis, structural studies, assembly of purified recombinant Gag, assembly of newly translated Gag in a cell-free system, and studies in cells using biochemical and imaging techniques. We summarize key findings obtained using each approach, point out where there is consensus, and highlight unanswered questions. Particular emphasis is placed on reconciling data suggesting that Gag assembles by two different paths, depending on the assembly environment. Specifically, in assembly systems that lack cellular proteins, high concentrations of Gag can spontaneously assemble using purified nucleic acid as a scaffold. However, in the more complex intracellular environment, barriers that limit self-assembly are present in the form of cellular proteins, organelles, host defenses, and the absence of free nucleic acid. To overcome these barriers and promote efficient immature capsid formation in an unfavorable environment, Gag appears to utilize an energy-dependent, host-catalyzed, pathway of assembly intermediates in cells. Overall, we show how data obtained using a variety of techniques has led to our current understanding of HIV assembly.

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  • Concomitant with or after budding, activation of the viral protease leads to cleavage of Gag at specific positions, inducing major structural rearrangements of the individual Gag domains and a dramatic change in virus morphology.

    “Concomitant with or after budding, activation of the viral protease leads to cleavage of Gag at specific positions, inducing major structural rearrangements of the individual Gag domains and a dramatic change in virus morphology”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [3]

    Section 3.1 says HIV-1 protease cleaves Gag simultaneous with or just after release of the immature virus; the Introduction identifies this cleavage as part of maturation after budding. Section 3.5 reports substantially different CA interfaces in immature and mature capsids. Our copy does not establish that cleavage induces major rearrangements of the individual Gag domains or a dramatic change in overall virus morphology. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Proteolytic cleavages catalysed by the viral protease lead to a spectacular structural rearrangement of the viral particle into a mature form that is competent to fuse with and infect a new cell.

    “Subsequently, a series of proteolytic cleavages catalysed by the viral protease leads to a spectacular structural rearrangement of the viral particle into a mature form that is competent to fuse with and infect a new cell.”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [3]

    The Introduction (§1.1; page unavailable) says maturation into infectious virus involves cleavage of Gag by HIV-1 protease. The structural-biology discussion (§3.5; page unavailable) reports substantial differences between immature and mature capsid interfaces. Our copy does not specifically say that cleavage produces a particle competent to fuse with a new cell. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Lingappa, J. R., Reed, J. C., Tanaka, M., Chutiraka, K., & Robinson, B. A.
Affiliations
University of Washington (US)
Corresponding author
Lingappa, Jaisri R.
ORCID
Venue
Virus Research
Publisher
Elsevier BV
Published
2014-11
Volume
193
Pages
89-107
ISSN
0168-1702 (ISSN-L)
DOI
10.1016/j.virusres.2014.07.001
PMC
PMC4351045
OpenAlex
W2049372909
Cited by
91
References
20
Citations by year
2026: 4 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 13 · 2020: 10 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 7 · 2015: 8
FWCI
3.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Virus Research (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Fred Hutchinson Cancer Research Center
  • NIH
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
HIV-1 Gag, viral assembly, nucleocapsid, assembly intermediates, HIV-1 life cycle
MeSH terms
Cell-Free System, Humans, Mutation, Structure-Activity Relationship, Virus Replication, HIV-1, Virus Assembly, RNA Interference, Capsid Proteins, gag Gene Products, Human Immunodeficiency Virus, Protein Interaction Domains and Motifs, Gene Knockdown Techniques, Molecular Imaging, In Vitro Techniques

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