title: Evidence that HIV-1 restriction factor SAMHD1 facilitates differentiation of myeloid THP-1 cells.
abstract: BACKGROUND
  SAMHD1 counteracts HIV-1 or HIV-2/SIVsmm that lacks Vpx by depleting the intracellular pool of nucleotides in myeloid cells and CD4+ quiescent T cells, thereby inhibiting the synthesis of retroviral DNA by reverse transcriptase. Depletion of nucleotides has been shown to underline the establishment of quiescence in certain cellular systems. These observations led us to investigate whether SAMHD1 could control the transition between proliferation and quiescence using the THP-1 cell model.
  
  
  RESULTS
  The entry of dividing THP-1 myeloid cells into a non-dividing differentiated state was monitored after addition of phorbol-12-myristate-13-acetate (PMA), an inducer of differentiation. Under PMA treatment, cells overexpressing SAMHD1 display stronger and faster adhesion to their support, compared to cells expressing a catalytically inactive form of SAMHD1, or cells depleted of SAMHD1, which appear less differentiated. After PMA removal, cells overexpressing SAMHD1 maintain low levels of cyclin A, in contrast to other cell lines. Interestingly, SAMHD1 overexpression slightly increases cell adhesion even in the absence of the differentiation inducer PMA. Finally, we found that levels of SAMHD1 are reduced in proliferating primary CD4+ T cells after T cell receptor activation, suggesting that SAMHD1 may also be involved in the transition from a quiescent state to a dividing state in primary T cells.
  
  
  CONCLUSIONS
  Altogether, we provide evidence that SAMHD1 may facilitate some aspects of THP-1 cell differentiation. Restriction of HIV-1 by SAMHD1 may rely upon its ability to modify cell cycle parameters, in addition to the direct inhibition of reverse transcription.
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. loic.dragin@inserm.fr.|CNRS, UMR8104, Paris, France. loic.dragin@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. loic.dragin@inserm.fr.
authors.forename: Loic
authors.initials: L
authors.lastname: Dragin
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. soundasse.munir-matloob@inserm.fr.|CNRS, UMR8104, Paris, France. soundasse.munir-matloob@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. soundasse.munir-matloob@inserm.fr.
authors.forename: Soundasse
authors.initials: S
authors.lastname: Munir-Matloob
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. jeanne.froehlich@inserm.fr.|CNRS, UMR8104, Paris, France. jeanne.froehlich@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. jeanne.froehlich@inserm.fr.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Froehlich
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. marina.morel@inserm.fr.|CNRS, UMR8104, Paris, France. marina.morel@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. marina.morel@inserm.fr.
authors.forename: Marina
authors.initials: M
authors.lastname: Morel
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. adele.sourisce@gmail.com.|CNRS, UMR8104, Paris, France. adele.sourisce@gmail.com.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. adele.sourisce@gmail.com.
authors.forename: Adèle
authors.initials: A
authors.lastname: Sourisce
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. hichem.lahouassa@inserm.fr.|CNRS, UMR8104, Paris, France. hichem.lahouassa@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. hichem.lahouassa@inserm.fr.
authors.forename: Hichem
authors.initials: H
authors.lastname: Lahouassa
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. karine.bailly@inserm.fr.|CNRS, UMR8104, Paris, France. karine.bailly@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. karine.bailly@inserm.fr.
authors.forename: Karine
authors.initials: K
authors.lastname: Bailly
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. marianne.mangeney@inserm.fr.|CNRS, UMR8104, Paris, France. marianne.mangeney@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. marianne.mangeney@inserm.fr.
authors.forename: Marianne
authors.initials: M
authors.lastname: Mangeney
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. cecilia.ramirez@inserm.fr.|CNRS, UMR8104, Paris, France. cecilia.ramirez@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. cecilia.ramirez@inserm.fr.
authors.forename: Bertha Cecilia
authors.initials: BC
authors.lastname: Ramirez
authors.affiliation: Inserm, U1016, Institut Cochin, 22 rue Méchain, 75014, Paris, France. florence.margottin-goguet@inserm.fr.|CNRS, UMR8104, Paris, France. florence.margottin-goguet@inserm.fr.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France. florence.margottin-goguet@inserm.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Margottin-Goguet
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D000076106:SAM Domain and HD Domain-Containing Protein 1; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000378:metabolism; D014779:Virus Replication
chemical_list: C016658:phorbolol myristate acetate; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate