title: Production of HIV-1 by resting memory T lymphocytes.
abstract: BACKGROUND
  The persistence of HIV-1 within resting memory CD4 T cells constitutes a major obstacle in the control of HIV-1 infection.
  
  
  OBJECTIVE
  To examine the expression of HIV-1 in resting memory CD4 T cells, using an in-vitro model.
  
  
  METHODS
  Phytohaemagglutinin-activated peripheral blood mononuclear cells were challenged with T cell-tropic and macrophage-tropic HIV-1 clones, and with a replication-incompetent and non-cytotoxic HIV-1-derived vector (HDV) pseudotyped by the vesicular stomatitis virus glycoprotein G. To obtain resting memory CD4 T cells containing HIV-1 provirus, residual CD25(+), CD69(+) and HLA-DR(+) cells were immunodepleted after a 3 week cultivation period.
  
  
  RESULTS
  In spite of the resting phenotype, the majority of provirus-harbouring T cells expressed HIV-1 genomes and produced infectious virus into cell-free supernatant. The expression of HDV dropped by only 30% during the return of activated HDV-challenged cells into the quiescent phase. Although resting memory T cells generated in vitro expressed HIV-1 and HDV genome when infected during the course of the preceding T cell activation, they were resistant to HIV-1 and HDV challenge de novo. The infected culture of resting memory T cells showed a higher resistance to the cytotoxic effects of HIV-1 in comparison with the same cultures after reactivation by phytohaemagglutinin.
  
  
  CONCLUSIONS
  The majority of resting memory T cells infected during the course of a preceding cell activation produces virus persistently, without establishing a true HIV-1 latency. The described system could be used as a model for testing new drugs able to control residual HIV-1 replication in resting memory T cells.
authors.affiliation: INSERM U372, Unité de Pathogénie des Infections à Lentivirus, Parc Scientifique et Technologique de Luminy, 13276 Marseille.
authors.forename: F
authors.initials: F
authors.lastname: Gondois-Rey
authors.forename: A
authors.initials: A
authors.lastname: Biancotto
authors.forename: M
authors.initials: M
authors.lastname: Pion
authors.forename: A L
authors.initials: AL
authors.lastname: Chenine
authors.forename: P
authors.initials: P
authors.lastname: Gluschankof
authors.forename: V
authors.initials: V
authors.lastname: Horejsi
authors.forename: C
authors.initials: C
authors.lastname: Tamalet
authors.forename: R
authors.initials: R
authors.lastname: Vigne
authors.forename: I
authors.initials: I
authors.lastname: Hirsch
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D005822:Genetic Vectors; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D017735:Virus Latency; D014779:Virus Replication