IFN-λ4 Attenuates Antiviral Responses by Enhancing Negative Regulation of IFN Signaling

The Journal of Immunology : Official Journal of the American Association of Immunologists
Adeola A ObajemuOlusegun O Onabajo

Abstract

Type III IFNs are important mediators of antiviral immunity. IFN-λ4 is a unique type III IFN because it is produced only in individuals who carry a dG allele of a genetic variant rs368234815-dG/TT. Counterintuitively, those individuals who can produce IFN-λ4, an antiviral cytokine, are also less likely to clear hepatitis C virus infection. In this study, we searched for unique functional properties of IFN-λ4 that might explain its negative effect on hepatitis C virus clearance. We used fresh primary human hepatocytes (PHHs) treated with recombinant type III IFNs or infected with Sendai virus to model acute viral infection and subsequently validated our findings in HepG2 cell line models. Endogenous IFN-λ4 protein was detectable only in Sendai virus-infected PHHs from individuals with the dG allele, where it was poorly secreted but highly functional, even at concentrations < 50 pg/ml. IFN-λ4 acted faster than other type III IFNs in inducing antiviral genes, as well as negative regulators of the IFN response, such as USP18 and SOCS1 Transient treatment of PHHs with IFN-λ4, but not IFN-λ3, caused a strong and sustained induction of SOCS1 and refractoriness to further stimulation with IFN-λ3. Our results suggest unique functional p...Continue Reading

References

Dec 7, 2002·Nature Immunology·Paul SheppardKevin M Klucher
Dec 17, 2002·Nature Immunology·Sergei V KotenkoRaymond P Donnelly
May 26, 2007·Nature Reviews. Immunology·Akihiko YoshimuraMasato Kubo
Apr 23, 2008·Current Protocols in Protein Science·Ira Palmer, Paul T Wingfield
Aug 19, 2008·Seminars in Cell & Developmental Biology·Ben A CrokerSandra E Nicholson
Nov 7, 2008·Genes and Immunity·C DellgrenR Hartmann
Sep 15, 2009·Nature Genetics·Vijayaprakash SuppiahJacob George
Sep 18, 2009·Nature·David L ThomasMary Carrington
Jul 30, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Svetlana MarukianLynn B Dustin
Feb 15, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lorenzo UccelliniThomas R O'Brien
Dec 15, 2012·Antiviral Research·Run-Xuan ShaoRaymond T Chung
Aug 6, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nikolaus JilgRaymond T Chung
Aug 10, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christopher R BolenSteven H Kleinstein
Aug 21, 2013·The Journal of Infectious Diseases·Peter V AkaThomas R O'Brien
Mar 6, 2015·Nature Communications·Mohammed EslamUNKNOWN International Hepatitis C Genetics Consortium (IHCGC)
Apr 24, 2015·Science Translational Medicine·Helen M LazearMichael S Diamond
Jun 16, 2015·Nature Genetics·Linda E KelemenUNKNOWN Ovarian Cancer Association Consortium
Jul 3, 2015·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Olusegun O OnabajoLudmila Prokunina-Olsson
Jul 22, 2015·Nature Immunology·Andreas WackRune Hartmann

❮ Previous
Next ❯

Citations

Jul 19, 2018·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ahmed LasfarKarine A Cohen-Solal
Oct 6, 2018·The Journal of Infectious Diseases·Claudia Jaimes-BernalAntonio Caruz
Apr 19, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Thomas R O'BrienLudmila Prokunina-Olsson
May 10, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ludmila Prokunina-Olsson
Jun 5, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Sreedhar Chinnaswamy, Marek L Kowalski
Jun 27, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Olusegun O OnabajoLudmila Prokunina-Olsson
Feb 23, 2020·Expert Review of Clinical Immunology·Claudio FeniziaMara Biasin
Aug 4, 2018·Frontiers in Microbiology·Guangyun TanGenhong Cheng
Apr 12, 2020·International Journal of Molecular Sciences·Pil Soo Sung, Eui-Cheol Shin
May 21, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Helen PiontkivskaMarta L Wayne
Dec 5, 2019·Tropical Diseases, Travel Medicine and Vaccines·Sergey YegorovRupert Kaul
Apr 3, 2019·Nature Microbiology·Emily V MesevAlexander Ploss
Oct 21, 2020·Nature Genetics·Olusegun O OnabajoLudmila Prokunina-Olsson
Jul 18, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wei TangStefan Ambs
Feb 20, 2021·Scandinavian Journal of Gastroenterology·Sidsel StøyThomas D Sandahl
Apr 23, 2021·Malaria Journal·Gabriela Samayoa-ReyesRosemary Rochford
Sep 10, 2021·Frontiers in Immunology·Olusegun O OnabajoLudmila Prokunina-Olsson
Nov 1, 2020·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Amany A SakrOsama M Ahmed

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Related Papers

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Thomas R O'BrienRaymond P Donnelly
Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Ashley PaquinLudmila Prokunina-Olsson
Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Olusegun O OnabajoLudmila Prokunina-Olsson
© 2022 Meta ULC. All rights reserved