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• W3214307463 endingPage "2247" @default.
• W3214307463 startingPage "2247" @default.
• W3214307463 abstract "The paucity of animal models that simulate the replication of the hepatitis B virus (HBV) is an impediment to advancing new anti-viral treatments. The work reported here employed recombinant adeno-associated viruses (AAVs) to model HBV subgenotype A1 and subgenotype D3 replication in vitro and in vivo. Infection with subgenotype A1 is endemic to parts of sub-Saharan Africa, and it is associated with a high risk of hepatocellular carcinoma. Recombinant AAV serotype 2 (AAV2) and 8 (AAV8) vectors bearing greater-than-genome-length sequences of HBV DNA from subgenotype A1 and D3, were produced. Transduced liver-derived cultured cells produced HBV surface antigen and core antigen. Administration of AAV8 carrying HBV subgenotype A1 genome (AAV8-A1) to mice resulted in the sustained production of HBV replication markers over a six-month period, without elevated inflammatory cytokines, expression of interferon response genes or alanine transaminase activity. Markers of replication were generally higher in animals treated with subgenotype D3 genome-bearing AAVs than in those receiving the subgenotype A1-genome-bearing vectors. To validate the use of the AAV8-A1 murine model for anti-HBV drug development, the efficacy of anti-HBV artificial primary-microRNAs was assessed. Significant silencing of HBV markers was observed over a 6-month period after administering AAVs. These data indicate that AAVs conveniently and safely recapitulate the replication of different HBV subgenotypes, and the vectors may be used to assess antivirals' potency." @default.
• W3214307463 created "2021-11-22" @default.
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• W3214307463 date "2021-11-09" @default.
• W3214307463 modified "2023-09-26" @default.
• W3214307463 title "In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors" @default.
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• W3214307463 doi "https://doi.org/10.3390/v13112247" @default.
• W3214307463 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8618177" @default.
• W3214307463 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34835053" @default.
• W3214307463 hasPublicationYear "2021" @default.
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