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Cited by 201HIV Research and TreatmentT-cell and Retrovirus StudiesHIV/AIDS drug development and treatment

The late domain of human immunodeficiency virus Type 1 p6 promotes virus release in a cell type-dependent manner

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Demirov, Dimiter G., Orenstein, Jan M., Freed, Eric O.·2002·Journal of Virology
DOI 10.1128/jvi.76.1.105-117.2002PMC PMC135729
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Abstract

The p6 domain of human immunodeficiency virus type 1 (HIV-1) is located at the C terminus of the Gag precursor protein Pr55 Gag . Previous studies indicated that p6 plays a critical role in HIV-1 particle budding from virus-expressing HeLa cells. In this study, we performed a detailed mutational analysis of the N terminus of p6 to map the sequences required for efficient virus release. We observed that the highly conserved P-T/S-A-P motif located near the N terminus of p6 is remarkably sensitive to change; even conservative mutations in this sequence imposed profound virus release defects in HeLa cells. In contrast, single and double amino acid substitutions outside the P-T/S-A-P motif had no significant effect on particle release. The introduction of stop codons one or two residues beyond the P-T/S-A-P motif markedly impaired virion release, whereas truncation four residues beyond P-T/S-A-P had no effect on particle production in HeLa cells. By examining the effects of p6 mutation in biological and biochemical analyses and by electron microscopy, we defined the role of p6 in particle release and virus replication in a panel of T-cell and adherent cell lines and in primary lymphocytes and monocyte-derived macrophages. We demonstrated that the effects of p6 mutation on virus replication are markedly cell type dependent. Intriguingly, even in T-cell lines and primary lymphocytes in which p6 mutations block virus replication, these changes had little or no effect on particle release. However, p6-mutant particles produced in T-cell lines and primary lymphocytes exhibited a defect in virion-virion detachment, resulting in the production of tethered chains of virions. Virus release in monocyte-derived macrophages was markedly inhibited by p6 mutation. To examine further the cell type-specific virus release defect in HeLa versus T cells, transient heterokaryons were produced between HeLa cells and the Jurkat T-cell line. These heterokaryons display a T-cell-like phenotype with respect to the requirement for p6 in particle release. The results described here define the role of p6 in virus replication in a wide range of cell types and reveal a strong cell type-dependent requirement for p6 in virus particle budding.

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Authors
Demirov, D. G., Orenstein, J. M., & Freed, E. O.
Affiliations
  • National Institutes of Health (US)
  • George Washington University (US)
ORCID
Venue
Journal of Virology
Publisher
American Society for Microbiology
Published
2002-01
Volume
76
Issue
1
Pages
105-117
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
DOI
10.1128/jvi.76.1.105-117.2002
PMC
PMC135729
OpenAlex
W2056548409
Cited by
201
References
67
Citations by year
2025: 3 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 8 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 6 · 2013: 9 · 2012: 10
FWCI
5.70
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Journal of Virology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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
Pr55gag, viral budding, particle release, cell type dependence, viral replication, monocyte-derived macrophages, T cell lines, heterokaryons, HeLa cells, primary lymphocytes
MeSH terms
Amino Acid Sequence, Cells, Cultured, Eukaryotic Cells, HeLa Cells, Humans, Lymphocytes, Macrophages, Molecular Sequence Data, Virus Replication, HIV-1, Gene Products, gag, Mutagenesis, Site-Directed, Codon, Terminator, Jurkat Cells, gag Gene Products, Human Immunodeficiency Virus

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