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Linking IFNα to apolipoprotein A-I provides a novel therapy of chronic hepadnavirus infection

 

Chronic hepatitis B (CHB) is a worldwide health problem results from the infection of hepatitis B virus (HBV). Traditional treatment strategies such as nucleioside/nucleitide analogues (NAs) are limited in reducing HBV surface antigen serum levels for immunostimulation, lead to a prolonged or even life-long treatment of HBV. An alternative therapy, pegylated interferon alpha (IFNα), stimulates immune clearance of HBV-infected hepatocytes, but limited due to poor response rates and severe side effects. Previously, Berrondo et al. demonstrated a molecule called InterApo (IA) with IFNα links to apolipoprotein A-I, has antiviral and immunostimulatory activities and lacks IFNα-induced hematological toxicity. In this study, they further explore the safety of IA for chronic HBV infection. The article is going to be published in Journal of Hepatology.

 

Researchers compared effectiveness between an adeno-associated vector encoding IA (AAV-IA) and a vector encoding only IFNα (AAV-IFN) in HBV transgenic mice and woodchucks with chronic woodchucks hepatitis virus (WHV). In the former animal models, two types of vectors both reduced serum and hepatic HBV DNA as well as hepatic HBV RNA, however, AAV-IFN caused lethal reduction of blood cells. WHV-infected woodchucks well tolerated on AAV-wIA, while experienced high mortality when using AAV-wIFN. In addition, control vetor encoding woodchuck apolipoprotein A-I (AAV-wApo) caused an immediate rebound in combination with entecavir. These findings suggest a outstanding effect and safety of AAV-IA treatment in chronic hepadnavirus infected animal models.

 

Reference:
J Hepatol. 2015 Mar 12. pii: S0168-8278(15)00171-3.

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