title: Blimp-1 overexpression is associated with low HIV-1 reservoir and transcription levels in central memory CD4+ T cells from elite controllers.
abstract: OBJECTIVE
  The aim of the study was to determine the molecular mechanisms underlying the quasi-equilibrium between HIV and its host in the model of functional cure represented by elite controllers who spontaneously maintain exceptionally low levels of HIV reservoirs.
  
  
  METHODS
  Whole-genome transcriptional study and quantification of the cell-associated HIV DNA and HIV RNA levels of the four major resting CD4 T-cell subsets in HIV-1-infected elite controllers, viremic long-term nonprogressors (vir-LTNPs), and uninfected individuals.
  
  
  METHODS
  We compared the whole-genome transcriptional profiles (ArrayExpress accession number E-MTAB-1480) of the four major resting CD4 T-cell subsets [naive (TN), central-memory (TCM), transitional-memory (TTM), and effector-memory (TEM)] from 14 HIV-1-infected individuals including seven elite controllers (E-LTNPs) and seven vir-LTNPs, and from seven uninfected individuals. The HIV-1 cellular DNA and mRNA levels were quantified in parallel in each sorted subset.
  
  
  RESULTS
  Host gene transcriptomes followed subset differentiation and viremia except in E-LTNPs wherein TCM, the main CD4 cell compartment, showed the highest activity with three specific signatures involving overexpression of T-cell receptor and costimulation signaling pathways, overexpression of the PRDM-1/Blimp-1 transcriptional repressor, and downmodulation of type-I IFN-related genes. Among subsets, the PRDM1/Blimp-1 upregulation was associated with lower levels of both cellular HIV-DNA and HIV mRNA levels.
  
  
  CONCLUSIONS
  This unique Blimp-1 transcriptional repressor signature and the contrast between host and virus transcriptional activities in TCM from elite controllers suggest Blimp-1 might be involved in controlling the HIV reservoirs in the key TCM subset.
authors.affiliation: aLaboratoire «Immunité et Infection», INSERM UMRS 945, Hôpital Pitié-Salpêtrière bUniversité Paris VI Pierre et Marie Curie cLaboratoire de Virologie, Hôpital Necker Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, EA3620, AP-HP, Paris, France. *Adèle de Masson and Amos Kirilovsky equally contributed to this article.
authors.forename: Adèle
authors.initials: A
authors.lastname: de Masson
authors.forename: Amos
authors.initials: A
authors.lastname: Kirilovsky
authors.forename: Rima
authors.initials: R
authors.lastname: Zoorob
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fenoel
authors.forename: Véronique
authors.initials: V
authors.lastname: Morin
authors.forename: Anne
authors.initials: A
authors.lastname: Oudin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Descours
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D014158:Transcription, Genetic; D017735:Virus Latency
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1