Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160
Open accessAbstract
The synthesis and processing of the human immunodeficiency virus 1 (HIV-1) envelope precursor glycoprotein gp 160 was studied in an infected CD4+ lymphocytic cell line. Surprisingly, only a small percentage (5-15%) of gp160 is cleaved to produce the mature gp120 component. Intracellular sorting results in the transfer of most uncleaved gp160 to lysosomes, where it is degraded, while gp120 is transported to the cell surface and subsequently secreted. Cleavage of gp160 to generate gp120 occurs intracellularly and can be inhibited by NH4Cl. Taken together, these results indicate that intracellular cleavage of gp160 determines the intracellular transport and survival of the envelope glycoproteins necessary to produce infectious virus.
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The Env protein of retroviruses is synthesized from a singly spliced mRNA as a precursor protein, which is cleaved by cellular proteases into gp120 (SU) and gp41 (TM), forming the gp120-gp41 heterotrimer.
“Without exception, the Env protein of retroviruses is synthesized from a singly spliced mRNA as a precursor protein, which is then cleaved by cellular proteases into the external glycoprotein gp120 (SU), which noncovalently associates with the gp41 (TM) domain to form the gp120–gp41 heterotrimer (McCune et al. 1988, Willey et al. 1988, Freed and Martin 1995).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Willey et al. 1988
In HIV-1, the Env glycoproteins precursor, gp160, is cleaved in the Golgi by cellular furin or furin-like PRs into a mature surface glycoprotein gp120 and the transmembrane glycoprotein gp41.
“In case of HIV-1, the Env glycoproteins precursor, gp160, is cleaved in the Golgi by cellular furin or furin-like PRs into: (i) a mature surface glycoprotein gp120 and (ii) the transmembrane glycoprotein gp41”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Willey et al. 1988
Cites
Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism
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Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gpl60
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Wang, T. T., Hirons, A., Doerflinger, M., Morris, K. V., Ledger, S., Purcell, D. F. J., Kelleher, A. D., & Ahlenstiel, C. L. (2024) · Viruses · doi:10.3390/v16101616 · Cited by 22 · see citing works
Viral and host factors regulating HIV-1 envelope protein trafficking and particle incorporation
Anokhin, B., & Spearman, P. (2022) · Viruses · doi:10.3390/v14081729 · Cited by 21 · see citing works
Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“…from a singly spliced mRNA as a precursor protein, which is then cleaved by cellular proteases into the external glycoprotein gp120 (SU), which noncovalently associates with the gp41 (TM) domain to form the gp120–gp41 heterotrimer (McCune et al. 1988 , Willey et al. 1988 , Freed and Martin 1995 ).”
- Authors
- Willey, R. L., Bonifacino, J. S., Potts, B. J., Martin, M. A., & Klausner, R. D.
- Affiliations
- National Institute of Allergy and Infectious Diseases (US)
- ORCID
- Bonifacino, J S
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1988-12
- Volume
- 85
- Issue
- 24
- Pages
- 9580-9584
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC282803
- OpenAlex
- W2026318059
- Cited by
- 428
- References
- 1
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 9 · 2023: 11 · 2022: 9 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 11 · 2013: 9 · 2012: 10
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- HIV-1, gp160, gp120, envelope glycoprotein, proteolytic cleavage, intracellular sorting, lysosomal degradation, cell surface transport, protein secretion, CD4+ T cells
- MeSH terms
- Ammonium Chloride, Antigens, Differentiation, T-Lymphocyte, Cell Line, Humans, Kinetics, Models, Biological, Retroviridae Proteins, Viral Envelope Proteins, Leukemia, Lymphocytic, Chronic, B-Cell, HIV Envelope Protein gp120, HIV Envelope Protein gp160
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