Retroviruses human immunodeficiency virus and murine leukemia virus are enriched in phosphoinositides
Open accessAbstract
Retroviruses acquire a lipid envelope during budding from the membrane of their hosts. Therefore, the composition of this envelope can provide important information about the budding process and its location. Here, we present mass spectrometry analysis of the lipid content of human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV). The results of this comprehensive survey found that the overall lipid content of these viruses mostly matched that of the plasma membrane, which was considerably different from the total lipid content of the cells. However, several lipids are enriched in comparison to the composition of the plasma membrane: (i) cholesterol, ceramide, and GM3; and (ii) phosphoinositides, phosphorylated derivatives of phosphatidylinositol. Interestingly, microvesicles, which are similar in size to viruses and are also released from the cell periphery, lack phosphoinositides, suggesting a different budding mechanism/location for these particles than for retroviruses. One phosphoinositide, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ], has been implicated in membrane binding by HIV Gag. Consistent with this observation, we found that PI(4,5)P 2 was enriched in HIV-1 and that depleting this molecule in cells reduced HIV-1 budding. Analysis of mutant virions mapped the enrichment of PI(4,5)P 2 to the matrix domain of HIV Gag. Overall, these results suggest that HIV-1 and other retroviruses bud from cholesterol-rich regions of the plasma membrane and exploit matrix/PI(4,5)P 2 interactions for particle release from cells.
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In HIV-1, PIP2 is roughly three times more concentrated in the viral membrane compared to the plasma membrane.
“In HIV-1, (PIP2) is roughly three times more concentrated in the viral membrane compared to the plasma membrane”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Chan et al. 2008
HIV-1 virus particles harbor three times more PIP2 molecules than Gag molecules.
“virus particles harbor three times more PIP2 molecules than Gag molecules”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Chan et al. 2008
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- Authors
- Chan, R., Uchil, P. D., Jin, J., Shui, G., Ott, D. E., Mothes, W., & Wenk, M. R.
- Affiliations
- National University of Singapore (SG)
- Yale University (US)
- National Cancer Institute (US)
- Corresponding author
- Wenk, Markus R.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2008-11-15
- Volume
- 82
- Issue
- 22
- Pages
- 11228-11238
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2573248
- OpenAlex
- W2081618928
- Cited by
- 282
- References
- 65
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 13 · 2020: 10 · 2019: 12 · 2018: 12 · 2017: 7 · 2016: 18 · 2015: 20 · 2014: 23 · 2013: 26 · 2012: 31
- FWCI
- 8.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Funders
- National University of Singapore
- National Institutes of Health (n01co12400-79-0-22)
- Biomedical Research Council
- National Cancer Institute (N01-CO-012400, ND1-CO-12400, R01CA098727)
- National Institute of Allergy and Infectious Diseases (R21AI065284)
- H2020 European Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- retroviruses, HIV-1, murine leukemia virus, phosphoinositides, phosphatidylinositol 4,5-bisphosphate, viral budding, plasma membrane, cholesterol, ceramide, GM3 ganglioside, microvesicles, HIV Gag, matrix domain, membrane binding
- MeSH terms
- Animals, Cell Line, Cell Membrane, Cytoplasm, Humans, Lipids, Leukemia Virus, Murine, Phosphatidylinositols, Mass Spectrometry, HIV-1, Secretory Vesicles, Rats, gag Gene Products, Human Immunodeficiency Virus
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