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TY - JOUR AU - Eto, Toshiharu AU - Takahashi, Hiroshi PY - 1999 DA - 1999/05/01 TI - Enhanced inhibition of hepatitis B virus production by asialoglycoprotein receptor-directed interferon JO - Nature Medicine SP - 577 EP - 581 VL - 5 IS - 5 AB - Most chronic carriers of hepatitis B virus (HBV) do not respond to interferon (IFN) treatment. This limitation of IFN therapy may be due in part to scant expression of IFN receptor in the liver1,2. Because the asialoglycoprotein (ASGP) receptor is specifically expressed in the liver at high density3, the ASGP receptor-binding domain was generated within an N-glycosylated human IFN-β molecule4,5 by the removal of sialic acid to direct this cytokine to the liver. This modified IFN (asialo-IFN-β) demonstrated greater inhibition of HBV production in ASGP receptor-positive human liver cells transfected with a replication-competent HBV construct than did conventional IFN-α or IFN-β. Furthermore, the enhanced antiviral effect of asialo-IFN-β was supported by induction of the 2'-5' oligoadenylate synthetase, an indicator of IFN activity6, at a level significantly higher than that produced by conventional IFN-β. Moreover, mouse asialo-IFN-β profoundly reduced viremia in vivo in HBV-transfected athymic nude mice, in contrast to conventional IFN-β, which had no substantial effect. These experiments demonstrate that directing IFN to ASGP receptor facilitates its signaling in the liver and augments its antiviral effect, and is therefore useful in overcoming the limited antiviral effect of conventional IFNs. SN - 1546-170X UR - https://doi.org/10.1038/8462 DO - 10.1038/8462 ID - Eto1999 ER -