Volume 11 Supplement 1

16th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access

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

  • Ricardo Khouri1, 2,
  • Gilvaneia Silva-Santos2,
  • Lourdes Farre2,
  • Achilea Bittencourt3,
  • Anne-Mieke Vandamme1, 4 and
  • Johan Van Weyenbergh1, 2, 5Email author
Retrovirology201411(Suppl 1):O22

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

Published: 7 January 2014

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
(2)
CPqGM-FIOCRUZ
(3)
HUPES-UFBA
(4)
Centro de Malária e outras Doenças Tropicais and Unidade de Microbiologia, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa
(5)
Institute for Immunological Investigation, iii-INCT

Copyright

© Khouri et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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