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  • Oral presentation
  • Open Access

Superior antiviral and antiproliferative activity of IFN-beta vs. IFN-alpha in primary ATL cells occurs downstream of STAT1 signaling

  • 1, 2,
  • 2,
  • 2,
  • 3,
  • 1, 4 and
  • 1, 2, 5Email author
Retrovirology201411 (Suppl 1) :O22

https://doi.org/10.1186/1742-4690-11-S1-O22

  • Published:

Keywords

  • Ingenuity Pathway Analysis
  • Antiviral Gene
  • Essential Cytokine
  • Primary Mononuclear Cell

Adult T-cell leukemia (ATL) is an aggressive CD4+CD25+ leukemia with poor prognosis, which usually develops several decades after HTLV-1 infection. In contrast to HIV-infection, the treatment of HTLV-1-associated diseases rely on a limited number of drugs. For ATL, combination therapy with IFN-alpha+AZT has shown clinical benefit in the non-lymphoma subtypes. Type I IFNs (IFN-alpha/beta) are essential cytokines with proved anti-cancer and antiviral action in vitro and in vivo. Nonetheless, their mechanisms of action in HTLV-1 infection remain unclear and a side-by-side comparison of both type I IFNs has not been performed in ATL. We show, in short-term culture of primary mononuclear cells from ATL patients, that both IFNs cause increased apoptosis, exert an anti-proliferative and antiviral effect, and decrease pro-inflammatory cytokine levels. However, IFN-beta treatment was significantly more effective in inhibiting viral p19 protein levels and lymphoproliferation, as compared to IFN-alpha. This pronounced effect of IFN-beta was explained by an induction of a higher number of known IFN-stimulated genes and antiviral genes by microarray analysis (76 vs. 26 genes were selected with p<0.001 and >2-fold difference vs. control). In PBMCs from healthy donors, ATL patients as well as in HTLV-1-infected cell lines, both IFNs have comparable activity in phosphorylating STATs 1 through 5 (PhosFlow), although phospho-STAT1 levels were up to tenfold higher than phospho-STAT2 through 5. This predominant STAT1-mediated antiviral gene signature was confirmed by Ingenuity Pathway analysis. In conclusion, our data suggest the superior antiviral and antiproliferative activity of IFN-beta vs. IFN-alpha occurs downstream of STAT1 signaling.

Authors’ Affiliations

(1)
Rega Institute for Medical Research, Department of Microbiology and Immunology, K.U.Leuven, Belgium
(2)
CPqGM-FIOCRUZ, Salvador-Bahia, Brazil
(3)
HUPES-UFBA, Salvador, BA, Brazil
(4)
Centro de Malária e outras Doenças Tropicais and Unidade de Microbiologia, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal
(5)
Institute for Immunological Investigation, iii-INCT, Brazil

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