Comparison of the anti-duck hepatitis A virus activities of phosphorylated and sulfated Astragalus polysaccharides

Duck hepatitis A virus (DHAV) (Picornaviridae) causes an infectious disease in ducks which results in severe losses in duck industry. However, the proper antiviral supportive drugs for this disease have not been discovered. Polysaccharide is the main ingredient of Astragalus that has been demonstrated to directly and indirectly inhibit RNA of viruses replication. In this study, the antiviral activities of Astragalus polysaccharide (APS) and its derivatives against DHAV were evaluated and compared. APS was modified via the sodium trimetaphosphate and sodium tripolyphosphate (STMP-STPP) method and chlorosulfonic acid-pyridine method to obtain its phosphate (pAPS) and sulfate (sAPS), respectively. The infrared structures of APS, pAPS, and sAPS were analyzed with the potassium bromide disc method. Additionally, the antiviral activities were evaluated with the MTT ((4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method in vitro and the artificial inoculation method in vivo. The clinical therapy effects were evaluated by mortality rate, liver function-related biochemical indicators, and visual changes in pathological anatomy. The anti-DHAV proliferation effects of APS, pAPS, and sAPS on the viral multiplication process in cell and blood were observed with the reverse transcription-polymerase chain reaction method. The results revealed that pAPS inhibited DHAV proliferation more efficiently in the entire process of viral multiplication than APS and sAPS. Moreover, only pAPS significantly improved the survival rate to 33.5% and reduced the DHAV particle titer in the blood as well as liver lesions in clinical trials. The results indicated that pAPS exhibited greater anti-DHAV activity than APS and sAPS both in vitro and in vivo.

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Identification of the Hepatitis A Virus Internal Ribosome Entry Site: In Vivo and in Vitro Analysis of Bicistronic RNAs Containing the HAV 5′ Noncoding Region

Virology ◽

10.1006/viro.1993.1193 ◽

1993 ◽

Vol 193 (2) ◽

pp. 842-852 ◽

Cited By ~ 42

Author(s):

Michael J. Glass ◽

Xi-Yu Jia ◽

Donald F. Summers

Keyword(s):

Internal Ribosome Entry Site ◽

Hepatitis A ◽

Hepatitis A Virus ◽

Entry Site ◽

Internal Ribosome Entry ◽

Vitro Analysis ◽

Virus Internal Ribosome Entry ◽

In Vitro Analysis

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Hepatitis a virus: Growth characteristics of in vivo and in vitro propagated wild and attenuated virus strains

Journal of Medical Virology ◽

10.1002/jmv.1890140410 ◽

1984 ◽

Vol 14 (4) ◽

pp. 373-386 ◽

Cited By ~ 17

Author(s):

Daniel W. Bradley ◽

Charles A. Schable ◽

Karen A. McCaustland ◽

E. H. Cook ◽

Bert L. Murphy ◽

...

Keyword(s):

Hepatitis A ◽

Hepatitis A Virus ◽

Growth Characteristics ◽

Virus Growth ◽

Attenuated Virus ◽

Virus Strains

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Assessment of the Effect of Baicalin on Duck Virus Hepatitis

Current Molecular Medicine ◽

10.2174/1566524019666190405095301 ◽

2019 ◽

Vol 19 (5) ◽

pp. 376-386 ◽

Cited By ~ 1

Author(s):

Yun Chen ◽

Fangke Yao ◽

Ke Ming ◽

Jintong Shi ◽

Ling Zeng ◽

...

Keyword(s):

Hepatitis A Virus ◽

Antiviral Drug ◽

Economic Losses ◽

Virus Hepatitis ◽

Mechanism Study ◽

Curative Effect ◽

Chinese Medicinal Herb ◽

Duck Hepatitis

Background: Duck virus hepatitis (DVH) caused by duck hepatitis A virus type 1 (DHAV-1) is a malignant disease in ducklings, causing economic losses in the duck industry. However, there is still no antiviral drug against DHAV-1 in the clinic. Objective: Our aim is to investigate the anti-DHAV-1 effect of baicalin, which is a flavonoid derived from the Chinese medicinal herb huangqin (Scutellaria baicalensis Georgi). Methods: Here, we first detected its anti-DHAV-1 ability in vitro and in vivo. At the same time, the inhibition of baicalin on DHAV-1 reproduction was determined. Finally, we tested and verified the anti-oxidative and immuno-enhancing roles of baicalin on its curative effect on DVH. Results: Baicalin possessed anti-DHAV-1 effect. It improved the cytoactive of DEH which was infected by DHAV-1 as well as reduced the DHAV-1 reproduction in DEH. Under baicalin treatment, mortality of ducklings infected by DHAV-1 decreased, additionally the DHAV-1 level and liver injury in such ducklings were significantly reduced or alleviated. The in vitro mechanism study indicated baicalin inhibited DHAV-1 reproduction via interfering the viral replication and release. Furthermore, the in vivo mechanism study manifested both the anti-oxidative and immuno-enhancing abilities of baicalin, which played crucial roles in its curative effect on DVH. Conclusion: This study may provide a scientific basis for developing baicalin as one or a part of the anti-DHAV-1 drugs.

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Kinetics of hepatitis A virus replication in vivo and in vitro using negative-strand quantitative PCR

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-009-0759-8 ◽

2009 ◽

Vol 28 (10) ◽

pp. 1167-1176 ◽

Cited By ~ 10

Author(s):

V. S. Paula ◽

A. S. Perse ◽

L. A. Amado ◽

L. M. Morais ◽

S. M. B. Lima ◽

...

Keyword(s):

Quantitative Pcr ◽

Virus Replication ◽

Hepatitis A ◽

Hepatitis A Virus ◽

Negative Strand ◽

Kinetics Of

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Expression of Hepatitis A Virus Precursor Protein P3 in Vivo and in Vitro: Polyprotein Processing of the 3CD Cleavage Site

Virology ◽

10.1006/viro.1994.1063 ◽

1994 ◽

Vol 198 (2) ◽

pp. 524-533 ◽

Cited By ~ 23

Author(s):

Michael Tesar ◽

Inga Pak ◽

Xi-Yu Jia ◽

Oliver C. Richards ◽

Donald F. Summers ◽

...

Keyword(s):

Cleavage Site ◽

Hepatitis A ◽

Hepatitis A Virus ◽

Precursor Protein ◽

Polyprotein Processing

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Mutations in VP0 and 2C Proteins of Duck Hepatitis A Virus Type 3 Attenuate Viral Infection and Virulence

Vaccines ◽

10.3390/vaccines7030111 ◽

2019 ◽

Vol 7 (3) ◽

pp. 111 ◽

Cited By ~ 2

Author(s):

Wen ◽

Guo ◽

Sun ◽

Wang ◽

Cao ◽

...

Keyword(s):

Hepatitis A ◽

Hepatitis A Virus ◽

Clinical Signs ◽

Innate Immune ◽

Economic Losses ◽

Histopathological Analysis ◽

Immune Genes ◽

Duck Hepatitis ◽

Differential Infectivity

Duck hepatitis A virus (DHAV) is prevalent worldwide and has caused significant economic losses. As the predominant serotype in China, DHAV-3 has become a major challenge to the local duck industry. Here the genetics and pathogenesis of a virulent DHAV-3 strain and its embryo-passaged strain were assessed. There were only two amino acid substitutions (Y164N in VP0 protein and L71I in 2C protein) introduced during the adaptation process. The pathogenicity of these strains was further evaluated in vivo. Clinical signs, gross pathology, and histopathological analysis showed that the embryo-passaged strain was attenuated. Meanwhile, the viral RNA loads were significantly lower in the liver tissues of the ducklings infected with the attenuated strain. As expected, infection with the virulent and attenuated strains led to the activation of different innate immune genes. We suspected that the loss of replication efficiency in ducklings was responsible for the attenuation phenotype of the embryo-passaged strain. In addition, different innate immune responses in the liver of ducklings were at least partly responsible for the differential infectivity phenotype. These findings provide new insights into the genetics and pathogenesis of DHAV-3, which may aid the development of new vaccines and the implementation of immunization strategies.

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Virulent and attenuated strains of duck hepatitis A virus elicit discordant innate immune responses in vivo

Journal of General Virology ◽

10.1099/vir.0.070011-0 ◽

2014 ◽

Vol 95 (12) ◽

pp. 2716-2726 ◽

Cited By ~ 10

Author(s):

Cuiping Song ◽

Ying Liao ◽

Wei Gao ◽

Shengqing Yu ◽

Yingjie Sun ◽

...

Keyword(s):

Nitric Oxide ◽

Immune Responses ◽

Hepatitis A ◽

Hepatitis A Virus ◽

Transmembrane Protein ◽

Oligoadenylate Synthetase ◽

Strong Immune Response ◽

Duck Hepatitis ◽

Serum Aspartate Aminotransferase

Previous studies of duck hepatitis A virus infection have focused only on the pathogenicity and host response of one strain. Here, we show that the virulent SH strain and the attenuated FC64 strain induced varied pathogenicity, apoptosis and immune responses in the livers of 1-day-old ducklings. SH infection caused apoptosis and visible lesions in the liver; serum aspartate aminotransferase, alanine transaminase, alkaline phosphatase, γ-glutamyltransferase and total bilirubin activities were markedly upregulated; and ducklings died at 36 h post-infection (p.i.). However, FC64 infection did not induce significant symptoms or impair liver function, and all of the infected ducklings remained healthy. In addition, both virus strains replicated well in the liver, spleen and intestine, whilst the SH strain replicated more efficiently than FC64. IFN-γ, IL-2, inducible nitric oxide synthase and nitric oxide were strongly induced by SH infection, and may be associated with the pathogenicity of the SH strain. IFN-α, IFN-β, IFN-stimulated transmembrane protein 1, IFN-stimulated gene 12, 2′,5′-oligoadenylate synthetase-like and IL-6 were moderately induced by SH infection at 24 h p.i., and dramatically induced by FC64 infection at 36 h p.i. The intensive induction of cytokines by FC64 may be involved in restriction of virus replication and stimulation of adaptive immune responses. Ducklings inoculated with FC64 produced high levels of antiviral antibodies within 45 days p.i. The low virulence and strong immune response of FC64 rendered this strain a good vaccine candidate, as confirmed by a protective assay in this study.

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