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			PubMed Journals: Nat Med

  Source:		PMID: 10229237


    		Nat Med. 1999 May;5(5):577-81.
     
			Enhanced inhibition of hepatitis B virus
			production by asialoglycoprotein receptor-directed
			interferon.

			Eto T(1), Takahashi H.

			Author Information
			(1) Gastrointestinal Unit, Harvard Medical School
			and Massachusetts General Hospital, Boston
			02114, USA.

			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 liver. Because the
			asialoglycoprotein (ASGP) receptor is specifically
			expressed in the liver at high density,
			the ASGP receptor-binding domain was generated
			within an N-glycosylated human IFN-beta
			molecule by the removal of sialic acid to
			direct this cytokine to the liver. This
			modified IFN (asialo-IFN-beta) demonstrated
			greater inhibition of HBV production in
			ASGP receptor-positive human liver cells
			transfected with a replication-competent
			HBV construct than did conventional IFN-alpha
			or IFN-beta. Furthermore, the enhanced antiviral
			effect of asialo-IFN-beta was supported
			by induction of the 2'-5' oligoadenylate
			synthetase, an indicator of IFN activity,
			at a level significantly higher than that
			produced by conventional IFN-beta. Moreover,
			mouse asialo-IFN-beta profoundly reduced
			viremia in vivo in HBV-transfected athymic
			nude mice, in contrast to conventional IFN-beta,
			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.

			DOI: 10.1038/8462 PMID: 10229237 [Indexed
			for MEDLINE]

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