title: Interferon lambda inhibits dengue virus replication in epithelial cells.
abstract: BACKGROUND
  In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection.
  
  
  METHODS
  Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR.
  
  
  RESULTS
  We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression.
  
  
  CONCLUSIONS
  Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.
authors.affiliation: Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México. hk.palma@gmail.com.|Posgrado en Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, México. hk.palma@gmail.com.
authors.forename: Helen K
authors.initials: HK
authors.lastname: Palma-Ocampo
authors.affiliation: Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México. flores_alonso_jc@hotmail.com.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Flores-Alonso
authors.affiliation: Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México. veronica_vallejo@yahoo.com.
authors.forename: Verónica
authors.initials: V
authors.lastname: Vallejo-Ruiz
authors.affiliation: Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México. julio.reyes@imss.gob.mx.
authors.forename: Julio
authors.initials: J
authors.lastname: Reyes-Leyva
authors.affiliation: Laboratorio de Inmunología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, México. liliankarem@gmail.com.
authors.forename: Lilian
authors.initials: L
authors.lastname: Flores-Mendoza
authors.affiliation: Laboratorio de Bioquímica, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, México. irma.herrera@correo.buap.mx.
authors.forename: Irma
authors.initials: I
authors.lastname: Herrera-Camacho
authors.affiliation: Laboratorio de Bioquímica, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, México. nora.rosas@correo.buap.mx.
authors.forename: Nora H
authors.initials: NH
authors.lastname: Rosas-Murrieta
authors.affiliation: Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México. gerardo.santos.lopez@gmail.com.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Santos-López
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics; D000998:Antiviral Agents / Q000097:blood / Q000378:metabolism*; D003716:Dengue Virus / Q000276:immunology* / Q000502:physiology*; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology*; D020869:Gene Expression Profiling; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000097:blood / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*; D000095022:Interferon Lambda
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579071:MX1 protein, human; C475085:OAS1 protein, human