Bruegger, Britta and Krautkraemer, Ellen and Tibroni, Nadine and Munte, Claudia E. and Rauch, Susanne and Leibrecht, Iris and Glass, Baerbel and Breuer, Sebastian and Geyer, Matthias and Kraeusslich, Hans-Georg and Kalbitzer, Hans Robert and Wieland, Felix T. and Fackler, Oliver T. (2007) Human immunodeficiency virus type 1 nef protein modulates the lipid composition of virions and host cell membrane microdomains. RETROVIROLOGY, 4: 70. ISSN 1742-4690,
Full text not available from this repository. (Request a copy)Abstract
Background: The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. Results: Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. Conclusion: Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLYUNSATURATED FATTY-ACIDS; PATHOGENICITY FACTOR NEF; HIV-1 NEF; T-CELLS; IMMUNOLOGICAL SYNAPSE; PLASMA-MEMBRANE; P21-ACTIVATED KINASE; CHEMOKINE RECEPTORS; ENVELOPED VIRUSES; VIRAL INFECTIVITY; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Dec 2020 11:08 |
| Last Modified: | 11 Jan 2021 07:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32187 |
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