Abstract
The cellular prion protein PrPC/CD230 is a GPI-anchor protein highly expressed in cells from the nervous and immune systems and well conserved among vertebrates. In the last decade, several studies suggested that PrPC displays antiviral properties by restricting the replication of different viruses, and in particular retroviruses such as murine leukemia virus (MuLV) and the human immunodeficiency virus type 1 (HIV-1). In this context, we previously showed that PrPC displays important similarities with the HIV-1 nucleocapsid protein and found that PrPC expression in a human cell line strongly reduced HIV-1 expression and virus production. Using different PrPC mutants, we report here that the anti-HIV-1 properties are mostly associated with the amino-terminal 24-KRPKP-28 basic domain. In agreement with its reported RNA chaperone activity, we found that PrPC binds to the viral genomic RNA of HIV-1 and negatively affects its translation. Using a combination of biochemical and cell imaging strategies, we found that PrPC colocalizes with the virus assembly machinery at the plasma membrane and at the virological synapse in infected T cells. Depletion of PrPC in infected T cells and microglial cells favors HIV-1 replication, confirming its negative impact on the HIV-1 life cycle.
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Abbreviations
- HIV:
-
Human immunodeficiency virus
- GPI:
-
Glycosyl phosphatidyl inositol
- DRMs:
-
Detergent-resistant microdomains
- TEMs:
-
Tetraspanin-enriched microdomains
- TNTs:
-
Tuneling nanotubes
- UTR:
-
Untranslated region
- GFP:
-
Green fluorescent protein
- OR:
-
Octa repeat
- HC:
-
Hydrophobic core
- TM:
-
Transmembrane
- PLAP:
-
Placental alkaline phosphatase
- VSVg:
-
Vesicular stomatitis virus glycoprotein
- LVs:
-
Lentivectors
- ELISA:
-
Enzyme-linked immunosorbent assay
- KD:
-
Knock down
- FACS:
-
Fluorescent activated cell sorter
- WT:
-
Wild type
- RT:
-
Reverse transcriptase
- FL:
-
Full length
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Acknowledgments
We thank Ramanujan Hegde, David Harris, Paul Bieniasz, David Westaway, Jeremy Luban, Serge Bénichou, Didier Trono and Hybridolab for kindly providing biological materials. We thank Olivier Schwartz, Clarisse Berlioz-Torrent and Renaud Mahieux for materials, discussions and help. We thank Robin Buckland and Jenny T. Miller for carefully reading the manuscript. We acknowledge the PLATIM microscope platform at ENS Lyon (SFR Biosciences Gerland–Lyon Sud UMS34444/US8, France). This work was supported by the CNRS, INSERM and GIS-Prion. RSR and TO received grant support from ANRS and Conycit. We thank the ANR program EXOPRION (to PL and GR) for its essential contribution to the definitive version of this work.
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Alais, S., Soto-Rifo, R., Balter, V. et al. Functional mechanisms of the cellular prion protein (PrPC) associated anti-HIV-1 properties. Cell. Mol. Life Sci. 69, 1331–1352 (2012). https://doi.org/10.1007/s00018-011-0879-z
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DOI: https://doi.org/10.1007/s00018-011-0879-z