title: Low SAMHD1 expression following T-cell activation and proliferation renders CD4+ T cells susceptible to HIV-1.
abstract: OBJECTIVE
  HIV-1 replication depends on the state of cell activation and division. It is established that SAMHD1 restricts HIV-1 infection of resting CD4 T cells. The modulation of SAMHD1 expression during T-cell activation and proliferation, however, remains unclear, as well as a role for SAMHD1 during HIV-1 pathogenesis.
  
  
  METHODS
  SAMHD1 expression was assessed in CD4 T cells after their activation and in-vitro HIV-1 infection. We performed phenotype analyzes using flow cytometry on CD4 T cells from peripheral blood and lymph nodes from cohorts of HIV-1-infected individuals under antiretroviral treatment or not, and controls.
  
  
  RESULTS
  We show that SAMHD1 expression decreased during CD4 T-cell proliferation in association with an increased susceptibility to in-vitro HIV-1 infection. Additionally, circulating memory CD4 T cells are enriched in cells with low levels of SAMHD1. These SAMHD1 cells are highly differentiated, exhibit a large proportion of Ki67 cycling cells and are enriched in T-helper 17 cells. Importantly, memory SAMHD1 cells were depleted from peripheral blood of HIV-infected individuals. We also found that follicular helper T cells present in secondary lymphoid organs lacked the expression of SAMHD1, which was accompanied by a higher susceptibility to HIV-1 infection in vitro.
  
  
  CONCLUSIONS
  We demonstrate that SAMHD1 expression is decreased during CD4 T-cell activation and proliferation. Also, CD4 T-cell subsets known to be more susceptible to HIV-1 infection, for example, T-helper 17 and follicular helper T cells, display lower levels of SAMHD1. These results pin point a role for SAMHD1 expression in HIV-1 infection and the concomitant depletion of CD4 T cells.
authors.affiliation: aInserm, U955, Equipe 16 bFaculté de médecine, Université Paris Est cVaccine Research Institute (VRI), Créteil dUnité Virus et Immunité, Département de Virologie, Institut Pasteur, Paris, France eInfectious Diseases Unit, Department of Internal Medicine, University Medical Center, Hamburg-Eppendorf and Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg fGeneral, Visceral and Thoracic Surgery Department, University Medical Center Hamburg, Eppendorf, Germany gAP-HP, Hôpital H. Mondor - A. Chenevier, Service d'immunologie clinique et maladies infectieuses, Créteil, France hThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruffin
authors.forename: Vedran
authors.initials: V
authors.lastname: Brezar
authors.forename: Diana
authors.initials: D
authors.lastname: Ayinde
authors.forename: Cécile
authors.initials: C
authors.lastname: Lefebvre
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze Zur Wiesch
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Hakim
authors.initials: H
authors.lastname: Hocini
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lelievre
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.forename: Nabila
authors.initials: N
authors.lastname: Seddiki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001769:Blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D049109:Cell Proliferation; D002648:Child; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis*; D000076106:SAM Domain and HD Domain-Containing Protein 1; D014779:Virus Replication; D055815:Young Adult
chemical_list: D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins