title: Higher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication.
abstract: BACKGROUND
  Clinical studies have shown faster disease progression and stronger immune activation in human immunodeficiency virus (HIV)-1-infected females when compared with males for the same level of HIV-1 replication. Here we determine whether the elevated levels of HIV-1-induced interferon-alpha (IFN-α) production observed in females are associated with higher interferon-stimulated gene (ISG) expression levels in T cells, hence suggesting type-I IFN as a mechanism for the higher HIV-1-associated immune activation observed.
  
  
  METHODS
  T-cell and dendritic cell populations were isolated from treatment-naive chronically HIV-1-infected individuals enrolled in the Adult Clinical Trials Group 384 by fluorescence-activated cell sorting. The expression of 98 genes involved in Toll-like receptor and type I IFN signaling pathways were quantified using Nanostring technology.
  
  
  RESULTS
  Several ISGs were significantly correlated with HIV-1 viral load and/or CD4(+) T-cell count. Higher expression levels of a subset of these ISGs were observed in cells derived from females as compared to males after adjusting for viral load and were correlated to higher levels of T-cell activation.
  
  
  CONCLUSIONS
  These data show that higher IFN-α production is associated with higher ex vivo expression of several ISGs in females. This might contribute to higher levels of immune activation and the observed faster HIV-1 disease progression in females for a given level of viral replication.
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Harvard Medical School, Cambridge, MA 02139, USA.
authors.forename: J Judy
authors.initials: JJ
authors.lastname: Chang
authors.forename: Matt
authors.initials: M
authors.lastname: Woods
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lindsay
authors.forename: Erin H
authors.initials: EH
authors.lastname: Doyle
authors.forename: Morgane
authors.initials: M
authors.lastname: Griesbeck
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Chan
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016898:Interferon-alpha
keywords: HIV-1; T cells; Toll-like receptors; dendritic cells; immune activation; innate immunity; pathogenesis; sex differences; type I Interferon