Functional mechanisms of the cellular prion protein (PrP(C)) associated anti-HIV-1 properties

Cell Mol Life Sci. 2012 Apr;69(8):1331-52. doi: 10.1007/s00018-011-0879-z. Epub 2011 Nov 11.


The cellular prion protein PrP(C)/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 PrP(C) 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 PrP(C) displays important similarities with the HIV-1 nucleocapsid protein and found that PrP(C) expression in a human cell line strongly reduced HIV-1 expression and virus production. Using different PrP(C) 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 PrP(C) 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 PrP(C) colocalizes with the virus assembly machinery at the plasma membrane and at the virological synapse in infected T cells. Depletion of PrP(C) in infected T cells and microglial cells favors HIV-1 replication, confirming its negative impact on the HIV-1 life cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Cell Line
  • Cells, Cultured
  • GPI-Linked Proteins / genetics
  • Gene Expression
  • Gene Knockdown Techniques
  • Gene Products, gag / analysis
  • HIV-1 / genetics
  • HIV-1 / growth & development*
  • HIV-1 / metabolism
  • Humans
  • Mutation
  • PrPC Proteins / analysis
  • PrPC Proteins / chemistry
  • PrPC Proteins / genetics
  • PrPC Proteins / metabolism*
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • T-Lymphocytes / virology*


  • Antigens, CD
  • BST2 protein, human
  • GPI-Linked Proteins
  • Gene Products, gag
  • PrPC Proteins
  • RNA, Viral