Induction of antiviral cytidine deaminases does not explain the inhibition of hepatitis B virus replication by interferons

Stéphanie Jost; Priscilla Turelli; Bastien Mangeat; Ulrike Protzer; Didier Trono

doi:10.1128/JVI.02489-06

Induction of antiviral cytidine deaminases does not explain the inhibition of hepatitis B virus replication by interferons

J Virol. 2007 Oct;81(19):10588-96. doi: 10.1128/JVI.02489-06. Epub 2007 Jul 25.

Authors

Stéphanie Jost¹, Priscilla Turelli, Bastien Mangeat, Ulrike Protzer, Didier Trono

Affiliation

¹ School of Life Sciences and Frontiers in Genetics National Center for Competence in Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Abstract

Interferons (IFNs) play a major role in the control of hepatitis B virus (HBV), whether as endogenous cytokines limiting the spread of the virus during the acute phase of the infection or as drugs for the treatment of its chronic phase. However, the mechanism by which IFNs inhibit HBV replication has so far remained elusive. Here, we show that type I and II IFN treatment of human hepatocytes induces the production of APOBEC3G (A3G) and, to a lesser extent, that of APOBEC3F (A3F) and APOBEC3B (A3B) but not that of two other cytidine deaminases also endowed with anti-HBV activity, activation-induced cytidine deaminase (AID), and APOBEC1. Most importantly, we reveal that blocking A3B, A3F, and A3G by combining RNA interference and the virion infectivity factor (Vif) protein of human immunodeficiency virus does not abrogate the inhibitory effect of IFNs on HBV. We conclude that these cytidine deaminases are not essential effectors of IFN in its action against this pathogen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

APOBEC-1 Deaminase
APOBEC-3G Deaminase
Cell Line, Tumor
Cytidine Deaminase / antagonists & inhibitors
Cytidine Deaminase / genetics
Cytidine Deaminase / metabolism*
Cytokines / pharmacology
Cytosine Deaminase / antagonists & inhibitors
Cytosine Deaminase / genetics
Cytosine Deaminase / metabolism
HIV-1 / drug effects
Hepatitis B virus / drug effects*
Hepatitis B virus / physiology
Hepatocytes / drug effects*
Hepatocytes / enzymology
Humans
Interferon Type I / pharmacology*
Interferon-gamma / pharmacology*
Interferons
Minor Histocompatibility Antigens
Nucleoside Deaminases / antagonists & inhibitors
Nucleoside Deaminases / genetics
Nucleoside Deaminases / metabolism
RNA, Small Interfering / pharmacology
Repressor Proteins / antagonists & inhibitors
Repressor Proteins / genetics
Repressor Proteins / metabolism
Virus Replication / drug effects*

Substances

Cytokines
Interferon Type I
Minor Histocompatibility Antigens
RNA, Small Interfering
Repressor Proteins
Interferon-gamma
Interferons
Nucleoside Deaminases
APOBEC3F protein, human
Cytosine Deaminase
APOBEC-1 Deaminase
APOBEC1 protein, human
APOBEC-3G Deaminase
APOBEC3B protein, human
APOBEC3G protein, human
Cytidine Deaminase