Inhibition of hepatitis B virus replication during schistosoma mansoni infection in transgenic mice.
Although coinfection of hepatitis B virus (HBV) and Schistosoma mansoni is a frequent event in humans, little is known about the interactions between these two pathogens. S. mansoni infection induces T helper cell type 2 (Th2)-type cytokines in the liver of humans and mice. The intrahepatic induction of nitric oxide (NO) and Th1-type cytokines, such as interferon (IFN)-gamma and IFN-alpha/beta, inhibits HBV replication noncytopathically in the liver of transgenic mice. To examine whether S. mansoni infection and the accompanying induction of Th2-type cytokines could interfere with HBV replication in the liver, HBV transgenic mice were infected with S. mansoni. By 5 wk after infection, HBV replication disappeared concomitant with the intrahepatic induction of NO and Th1-type cytokines, and in the absence of Th2-type cytokines. By 6-8 wk after infection, HBV replication remained undetectable and this was associated with further induction of NO and Th1-type cytokines together with the appearance of Th2-type cytokines. The S. mansoni-dependent antiviral effect was partially blocked by genetically deleting IFN-gamma, although it was unaffected by deletion of IFN-alpha/beta. These results indicate that IFN-gamma (probably via NO) mediates most of this antiviral activity and that Th2-type cytokines do not counteract the antiviral effect of IFN-gamma. Similar events may suppress HBV replication during human S. mansoni infection.
McClary
H
H
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Koch
R
R
Chisari
F V
FV
Guidotti
L G
LG
D000818:Animals; D006515:Hepatitis B virus / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012555:Schistosomiasis mansoni / Q000821:virology*; D014779:Virus Replication
D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse