Toll-like receptor signaling inhibits hepatitis B virus replication in vivo.
Toll-like receptors (TLR) play a key role in innate immunity. To examine the ability of diverse TLRs to modulate hepatitis B virus (HBV) replication, HBV transgenic mice received a single intravenous injection of ligands specific for TLR2, TLR3, TLR4, TLR5, TLR7, and TLR9. All of the ligands except for TLR2 inhibited HBV replication in the liver noncytopathically within 24 h in a alpha/beta interferon-dependent manner. The ability of these TLR ligands to induce antiviral cytokines at the site of HBV replication suggests that TLR activation could represent a powerful and novel therapeutic strategy for the treatment of chronic HBV infection.
Isogawa
Masanori
M
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Robek
Michael D
MD
Furuichi
Yoshihiro
Y
Chisari
Francis V
FV
D000818:Animals; D005260:Female; D006513:Hepatitis B e Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008024:Ligands; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053633:Receptor, Interferon alpha-beta; D011956:Receptors, Cell Surface / Q000276:immunology*; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D014779:Virus Replication / Q000276:immunology*
D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta