title: Expression profile of host restriction factors in HIV-1 elite controllers.
abstract: BACKGROUND
  Several host-encoded antiviral factors suppress HIV-1 replication in a cell-autonomous fashion in vitro. The relevance of these defenses to the control of HIV-1 in vivo remains to be elucidated. We hypothesized that cellular restriction of HIV-1 replication plays a significant role in the observed suppression of HIV-1 in "elite controllers", individuals who maintain undetectable levels of viremia in the absence of antiretroviral therapy (ART). We comprehensively compared the expression levels of 34 host restriction factors and cellular activation levels in CD4+ T cells and sorted T cell subsets between elite controllers, HIV-1-infected (untreated) non-controllers, ART-suppressed, and uninfected individuals.
  
  
  RESULTS
  Expression of schlafen 11, a codon usage-based inhibitor of HIV-1 protein synthesis, was significantly elevated in CD4+ T cells from elite controllers as compared to both non-controllers (p = 0.048) and ART-suppressed individuals (p = 0.024), with this effect most apparent in central memory CD4+ T cells. Schlafen 11 expression levels were comparable between controllers and uninfected individuals. Cumulative restriction factor expression was positively correlated with CD4+ T cell activation (r² = 0.597, p < 0.0001), viral load (r² = 0.34, p = 0.015), and expression of ISG15 (r² = 0.73, p < 0.0001), a marker of interferon exposure. APOBEC3C, APOBEC3D, CTR9, TRIM26, and TRIM32 were elevated in elite controllers with respect to ART-suppressed individuals, while levels were comparable to uninfected individuals and non-controllers.
  
  
  CONCLUSIONS
  Host restriction factor expression typically scales with cellular activation levels. However, the elevated mRNA and protein expression of schlafen 11, despite low activation and viral load, violates the global pattern and may be a signature characteristic of HIV-1 elite control.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Mohsen
authors.forename: Rui André Saraiva
authors.initials: RA
authors.lastname: Raposo
authors.forename: Xutao
authors.initials: X
authors.lastname: Deng
authors.forename: Manqing
authors.initials: M
authors.lastname: Li
authors.forename: Teri
authors.initials: T
authors.lastname: Liegler
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Salama
authors.forename: Hussam El-Din A
authors.initials: Hel-D
authors.lastname: Ghanem
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
authors.forename: Michael
authors.initials: M
authors.lastname: David
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, USA. satish.pillai@ucsf.edu.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Pillai
mesh_terms: D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D009687:Nuclear Proteins; C576668:SLFN11 protein, human