title: Antagonistic antiviral activity between IFN-lambda and IFN-alpha against lethal Crimean-Congo hemorrhagic fever virus in vitro.
abstract: OBJECTIVE
  Crimean Congo Hemorrhagic fever virus (CCHFV) is the causative agent of Crimean-Congo hemorrhagic fever, a severe disease with a mortality rate of around 30% in humans. Previous studies demonstrate that pre-treatment with type I IFNs have an antiviral effect against CCHFV, while established CCHFV infection is almost insensitive to subsequent IFN-α treatment. No data concerning type III IFNs antiviral activity against CCHFV are available so far. The aim of the present study was to explore the capability of IFN-λ1 to inhibit the replication of CCHFV and the possible synergism/antagonism between IFN-α and IFN-λ1 both in the inhibition of CCHFV replication and in the activation of intracellular pathways of IFN response.
  
  
  METHODS
  Human A549 and HuH7 cells were treated with increasing amounts of IFN-λ1, or IFN-α or a combination of them, infected with CCHF; the extent of virus yield inhibition and the induction of MxA and 2'-5'OAS mRNA was measured.
  
  
  CONCLUSIONS
  Our study pointed out that type III IFN possess an antiviral activity against CCHFV, even if lower than type I IFN. Moreover, a clear antagonism between IFN-λ and IFN-α was observed in both cell lines (A549 and HuH7 cells), in terms of antiviral effect and activation of pivotal ISGs, i.e. MxA and 2'-5'OAS. Elucidating the interplay between type I and III IFNs will help to better understand innate defence mechanisms against viral infections and may provide novel scientific evidence for a more rational planning of available and future treatments, particularly against human diseases caused by high concern viruses.
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Licia
authors.initials: L
authors.lastname: Bordi
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lalle
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Caglioti
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Travaglini
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lapa
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Marsella
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Quartu
authors.affiliation: Division of Virology, National Center for Epidemiology, Budapest, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kis
authors.affiliation: Unit of Virology, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Arien
authors.affiliation: Department of Hygiene, Microbiology & Social Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Hartwig P
authors.initials: HP
authors.lastname: Huemer
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Meschi
authors.affiliation: Scientific Direction, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.affiliation: Laboratory of Microbiology and Biorepository, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Di Caro
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Capobianchi
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Castilletti
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007372:Interferons; D007378:Interleukins / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda