Počet záznamů: 1
Development and Characterization of a Chronic Hepatitis B Murine Model With a Mutation in the START Codon of an HBV Polymerase
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SYSNO ASEP 0570640 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Development and Characterization of a Chronic Hepatitis B Murine Model With a Mutation in the START Codon of an HBV Polymerase Tvůrce(i) Vaneková, Lenka (UOCHB-X) ORCID
Pimková Polidarová, Markéta (UOCHB-X) ORCID
Charvát, Vilém (UOCHB-X) ORCID
Vavřina, Zdeněk (UOCHB-X) ORCID
Veverka, Václav (UOCHB-X) RID, ORCID
Birkuš, Gabriel (UOCHB-X) ORCID
Brázdová, Andrea (UOCHB-X) ORCIDZdroj.dok. Physiological Research. - : Fyziologický ústav AV ČR, v. v. i. - ISSN 0862-8408
Roč. 72, č. 1 (2023), s. 37-47Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. CZ - Česká republika Klíč. slova chronic hepatitis B murine model ; HBsAg ; HBcAg ; pAAV system ; minicircle HBV Obor OECD Medicinal chemistry CEP EF16_019/0000729 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 001000024200004 EID SCOPUS 85150000682 DOI 10.33549/physiolres.934979 Anotace Chronic hepatitis B (CHB) is caused by the Hepatitis B virus (HBV) and affects millions of people worldwide. Developing an effective CHB therapy requires using in vivo screening methods, such as mouse models reflecting CHB based on hydrodynamic delivery of plasmid vectors containing a replication-competent HBV genome. However, long-term expression of HBV proteins is accompanied by production of progeny virions, thereby requiring a Biosafety Level (BSL) 3 animal facility. In the present study, we introduced a point mutation in the START codon of the HBV polymerase to develop a mouse model reflecting chronic hepatitis B infection without formation of viral progeny. We induced the mouse model by hydrodynamic injection of adeno-associated virus plasmid vector (pAAV) and minicircle plasmid (pMC) constructs into C57Bl/6 and C3H/HeN mouse strains, monitoring HBV antigens and antibodies in blood by enzyme-linked immunosorbent assay and analyzing liver expression of HBV core antigen by immunohistology. Persisting expression of viral antigens over 140 days (study endpoint) was observed only in the C3H/HeN mouse strain when using pAAV/1.2HBV-A and pMC/1.0HBV-D with pre-C and pre-S recombination sites. In addition, pAAV/1.2HBV-A in C3H/HeN sustained HBV core antigen positivity up to the study endpoint in C3H/HeN mice. Moreover, introducing the point mutation in the START codon of polymerase effectively prevented the formation of viral progeny. Our study establishes an accessible and affordable experimental paradigm for developing a robust mouse model reflecting CHB suitable for preclinical testing of anti-HBV therapeutics in a BSL2 animal facility Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2024 Elektronická adresa https://doi.org/10.33549/physiolres.934979
Počet záznamů: 1