Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics.

Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Research Abstract Details 

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Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Abstract Text:

Tobias Marcello,Arash Grakoui,Giovanna Barba-Spaeth,Erica S Machlin,Sergei V Kotenko,Margaret R MacDonald,Charles M Rice,

BACKGROUND & AIMS: Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Current therapy with pegylated interferon alpha (IFN-alpha) in combination with ribavirin is associated with adverse effects and often fails to induce a sustained response. IFN-lambdas, recently discovered IFN gene family members, exhibit antiviral and cell stimulatory activities similar to IFN-alpha. We aimed to determine whether IFN-lambda exhibits antiviral activity toward HCV and to compare the signal transduction and effector gene pathways with those of IFN-alpha. METHODS: Using the HCV replicon system and cell culture infectious reporter virus, we compared IFN-alpha and IFN-lambda effects on HCV RNA replication and protein expression, as measured by quantitative reverse-transcriptase polymerase chain reaction, luciferase expression, and Western blot. Receptor expression and signaling pathways were explored using flow cytometry and Western blot. IFN-alpha- and IFN-lambda-mediated gene expression changes were compared using microarray analyses. RESULTS: IFN-lambda exhibited dose- and time-dependent HCV inhibition, independent of types I and II IFN receptors. The kinetics of IFN-lambda-mediated signal transducers and activators of transcription (STAT) activation and induction of potential effector genes were distinct from those of IFN-alpha. IFN-lambda induced steady increases in levels of known interferon stimulated genes (ISGs), whereas IFN-alpha ISGs peaked early and declined rapidly. IFN-lambda inhibited replication of HCV genotypes 1 and 2 and enhanced the antiviral efficacy of subsaturating levels of IFN-alpha. CONCLUSIONS: These results demonstrate distinct differences in IFN-lambda- and IFN-alpha-induced antiviral states. Understanding these differences may prove useful for developing new HCV treatment strategies.

Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Publishing Authors By Initials

T Marcello,A Grakoui,G Barba-Spaeth,ES Machlin,SV Kotenko,MR MacDonald,CM Rice,

For similar biological phenomena, cell phenomena, and immunity: biological phenomena: microbiologic phenomena: viral physiology: virus replication research abstracts see: biological phenomena, cell phenomena, and immunity: biological phenomena: microbiologic phenomena: viral physiology: virus replication research

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Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Gastroenterology

VOLUME: 131

Page Numbers: 1887-98

Journal Abbreviation: Gastroenterology

ISSN: 0016-5085

DAY: 1

MONTH: 10

YEAR: 2006

Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 374630

Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Keywords Mesh Terms:

KEYWORDS: Virus Replication

MESH TERMS: drug effects

Chemical & Substance for Abstract: Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Information

Substance Name: interleukin 29 protein, human

Registry Number: 0

Grant and Affiliation Information for Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics.

AFFILIATION: Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10021, USA.

Country: United States

AGENCY: United States NCRR

GRANT: RR-00165

ACRONYM: RR

MEDLINETA: Gastroenterology

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