Human MxA protein participates to the interferon-related inhibition of hepatitis B virus replication in female transgenic mice.
OBJECTIVE
The interferon (IFN) inducible MxA protein is endowed with antiviral activity against a broad range of RNA viruses. In a previous in vitro study, we demonstrated that MxA inhibits hepatitis B virus (HBV) replication, arguing that the antiviral activity of MxA is not restricted to RNA viruses but also includes a DNA virus. The aim of the present study was to further demonstrate in vivo the antiviral action of MxA against HBV.


METHODS
We generated HBV and HBV/MxA transgenic mice lacking a functional IFN-alpha/beta receptor and thus constituting a good model to evaluate MxA-induced virus resistance. HBV proteins expression, viral load and HBV replication were compared in HBV and HBV/MxA mice.


RESULTS
An MxA-dependent moderate inhibitory effect on HBV expression was only observed in female HBV/MxA mice, in which MxA downregulates (i) viral HBeAg and capsid protein expression, (ii) viremia and (iii) HBV replication by decreasing the synthesis of HBV DNA replicative intermediates. Furthermore, these effects were not associated with changes to steady-state levels of HBV RNAs.


CONCLUSIONS
Our results show that in vivo, MxA is able per se to reduce HBV expression by a post-transcriptional mechanism, and thus participates in the antiviral activity of IFN-alpha against HBV.
Peltekian
Cécile
C
INSERM U370/Institut Pasteur, Faculté de Médecine Necker Enfants-Malades, 156, rue de Vaugirard, 75015 Paris, France.
Gordien
Emmanuel
E
Garreau
Florianne
F
Meas-Yedid
Vannary
V
Soussan
Patrick
P
Willams
Virginie
V
Chaix
Marie-Laure
ML
Olivo-Marin
Jean-Christophe
JC
Bréchot
Christian
C
Kremsdorf
Dina
D
D000818:Animals; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D064547:Myxovirus Resistance Proteins; D019562:Viral Load; D014764:Viral Proteins / Q000096:biosynthesis*; D014779:Virus Replication / Q000235:genetics*
D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D014764:Viral Proteins; D016899:Interferon-beta; D019204:GTP-Binding Proteins