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Antiviral effects of PNA in duck hepatitis B virus infection model.

Abstract

Aim: To study the efficacy of antiviral treatment with PNA for the duck model of HBV (DHBV)-infected ducks. PNA is a 2-amine-9-(2,3-dideoxy-2,3-dihydro-β-D-arabinofuranosyl)-6-methoxy-9 H -purine. Methods: The Sichuan Mallard ducklings in the hepatitis B virus model were treated with PNA, a new antiviral agent. DHBV DNA from the blood serum and liver tissues were measured at 0, 5, and 10 d during the treatment and at 3 d withdrawal by real-time PCR. The duck hepatitis B surface antigen (DHBsAg) in the liver cells was observed by Immunohistochemistry (IHC). Pathological changes in the liver tissues were also observed. Control group I was administered with distilled water and control group II was administered with 3-thiacytidine. Treatment group I was administered with PNA at a dose of 40 mg/kg and treatment group II was administered perorally( po ) with PNA at a dose of 80 mg/kg. Treatment group III was administered with PNA at a dose of 20 mg/kg and treatment group IV was intravenously administered with PNA at a dose of 40 mg/kg. Each group contained 15 ducklings.

Keywords:PNA (2-amine-9-(2,3-dideoxy-2,3-dihydro-β-D-arabinofuranosyl)-6-methoxy-9Hpurine); anti-Duck hepatitis B virus activity; duck hepatitis B virus

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Fig.1. Detection of congenitally DHBV-infected ducklings by PCR in serum samples. Lane 1, 100–600 bp size markers; lane 2, DHBV-positive control; lanes 3–6, serum samples; lane 7, negative control.

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Fig.2.Histopathological examinations of livers in ducklings treated with PNA at d 3 of withdrawal. Necrosis, steatosis, and swelling of the hepatic cytoplasm were found in control group I, as well as focal necrosis and vacuolar degeneration. Pathological changes in the treatment groups were obviously improved. A significant improvement of the hepatocellular architecture and a considerable reduction in necrosis and vacuolation were found. (A) Placebo group; (B) PNA 80 mg/kg, po group; (C) PNA 40 mg/kg, iv group; (D) 3TC 50 mg/kg, po. group. HE, final magnification ×400.

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Fig.3. Detection of DHBsAgpositive cells in the livers of ducks treated with PNA at d 3 of withdrawal. (A) Placebo group; (B) PNA 80 mg/kg, po, group; (C) PNA 40 mg/kg, iv, group; (D) 3TC 50 mg/kg, po, group. Final magnification ×400.

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