HIV-1 assembly, budding, and maturation
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A defining property of retroviruses is their ability to assemble into particles that can leave producer cells and spread infection to susceptible cells and hosts. Virion morphogenesis can be divided into three stages: assembly, wherein the virion is created and essential components are packaged; budding, wherein the virion crosses the plasma membrane and obtains its lipid envelope; and maturation, wherein the virion changes structure and becomes infectious. All of these stages are coordinated by the Gag polyprotein and its proteolytic maturation products, which function as the major structural proteins of the virus. Here, we review our current understanding of the mechanisms of HIV-1 assembly, budding, and maturation, starting with a general overview and then providing detailed descriptions of each of the different stages of virion morphogenesis.
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Virus particle release is driven by the viral structural polyprotein Gag, which directs particle assembly at the plasma membrane and facilitates membrane curvature to promote budding/release.
“This process is driven by the viral structural polyprotein Gag, which directs particle assembly at the plasma membrane and facilitates membrane curvature to promote budding/release”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Sundquist and Kräusslich 2012
Once a retrovirus completes its assembly, it buds off as an immature, noninfectious virion containing viral components as large polyproteins, primarily Gag and Gag-Pol (such as MLV and HIV-1) assembling at the plasma membrane, and Gag, Gag-Pro, and Gag-Pro-Pol (such as MPMV and MMTV), preassembling in the cytoplasm.
“Once a retrovirus completes its assembly, it buds off as an immature, noninfectious virion containing viral components as large polyproteins, primarily Gag and Gag–Pol (such as MLV and HIV-1) assembling at the plasma membrane (Fig. 5), and Gag, Gag–Pro, and Gag–Pro–Pol (such as MPMV and MMTV), preassembling in the cytoplasm”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Sundquist and Kräusslich 2012
Initially inactive, the retroviral PR undergoes autocatalytic activation upon budding, triggering a cascade of cleavage events that cleaves the Gag precursor polyprotein into the three main structural proteins, MA, CA, and NC.
“Initially inactive, the retroviral PR undergoes an autocatalytic activation upon budding, triggering a cascade of cleavage events that cleaves the Gag precursor polyprotein into the three main structural proteins, MA, CA, and NC”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Sundquist and Kräusslich 2012
Improper cleavage by the PR results in defective, noninfectious retroviral particles.
“Improper cleavage by the PR results in defective, noninfectious retroviral particles”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Sundquist and Kräusslich 2012
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“…PR undergoes an autocatalytic activation upon budding, triggering a cascade of cleavage events that cleaves the Gag precursor polyprotein into the three main structural proteins, MA, CA, and NC (Coffin 1997 , Sundquist and Kräusslich 2012 , Freed 2015 , Pornillos and Ganser-Pornillos 2019 ).”
Influential
- Authors
- Sundquist, W. I., & Krausslich, H.-G.
- Affiliations
- University of Utah (US)
- ORCID
- Sundquist, W. I.
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-03-13
- Volume
- 2
- Issue
- 7
- Pages
- a006924-a006924
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC3385941
- OpenAlex
- W2117867057
- Cited by
- 814
- References
- 16
- Citations by year
- 2026: 41 · 2025: 46 · 2024: 39 · 2023: 44 · 2022: 43 · 2021: 75 · 2020: 62 · 2019: 65 · 2018: 67 · 2017: 54 · 2016: 70 · 2015: 71 · 2014: 72 · 2013: 48 · 2012: 16
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SPP1175, SFB 638, SFB544)
- National Institutes of Health (GM082545)
- National Institute of General Medical Sciences (P50GM082545)
- National Institute of Allergy and Infectious Diseases (R01AI051174, R37AI045405)
- 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, viral assembly, budding, virus maturation, Gag protein, proteolytic processing, lipid envelope
- MeSH terms
- Viroporin Proteins, Capsid, Membrane Lipids, RNA, Viral, HIV-1, Gene Products, env, HIV Protease, Virus Assembly, Human Immunodeficiency Virus Proteins, gag Gene Products, Human Immunodeficiency Virus, Viral Regulatory and Accessory Proteins, Endosomal Sorting Complexes Required for Transport, Virus Release
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