title: Type III interferon (IFN-lambda) antagonizes the antiviral activity of interferon-alpha in vitro.
abstract: Type III interferons (IFN-lambda) are the most recently discovered members of IFN family. Synergism between different IFN types is well established, but for type I and type III IFNs no conclusive evidence has been reported so far. Possible synergism/antagonism between IFN-alpha and IFN-lambda in the inhibition of virus replication (EMCV, WNV lineage 1 and 2, CHIKV and HSV-1), and in the activation of intracellular pathways of IFN response (MxA and 2'-5' OAS) was evaluated in different cell lines (Vero E6, A549 and Wish cells). The antiviral potency of IFN-lambda1 and -l2 was lower than that of IFN-alpha. When IFN-alpha and -lambda were used together, the Combination Index (CI) for virus inhibition was greater than 1 virtually for all virus/host cell systems, indicating antagonistic effect. Antagonism between IFN-alpha and -l was also observed for the induction of mRNA for both MxA and 2'-5'OAS. Elucidating the interplay between IFN-alpha and -lambda may help to better understand innate defence mechanisms against viral infections, including the molecular mechanisms underlying the influence of IL-28B polymorphisms in the response to HCV and other viral infections.
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bordi
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Lalle
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Lapa
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Caglioti
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Quartu
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Capobianchi
authors.affiliation: Laboratory of Virology, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Castilletti
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D000818:Animals; D000998:Antiviral Agents / Q000037:antagonists & inhibitors*; D002522:Chlorocebus aethiops; D004686:Encephalomyocarditis virus / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors*; D007372:Interferons / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D064547:Myxovirus Resistance Proteins / Q000235:genetics; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D064547:Myxovirus Resistance Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579071:MX1 protein, human