In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors

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 vi...

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Autores principales:	Shonisani Wendy Limani, Njabulo Mnyandu, Abdullah Ely, Reubina Wadee, Anna Kramvis, Patrick Arbuthnot, Mohube Betty Maepa
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adeno-associated virus anti-viral gene therapy hepatitis B virus HBV mouse models Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/689e6cf075b94dd7a793c5b0db69c232
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spelling	oai:doaj.org-article:689e6cf075b94dd7a793c5b0db69c2322021-11-25T19:13:44ZIn Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors10.3390/v131122471999-4915https://doaj.org/article/689e6cf075b94dd7a793c5b0db69c2322021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2247https://doaj.org/toc/1999-4915The 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.Shonisani Wendy LimaniNjabulo MnyanduAbdullah ElyReubina WadeeAnna KramvisPatrick ArbuthnotMohube Betty MaepaMDPI AGarticleadeno-associated virusanti-viral gene therapyhepatitis B virusHBV mouse modelsMicrobiologyQR1-502ENViruses, Vol 13, Iss 2247, p 2247 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adeno-associated virus anti-viral gene therapy hepatitis B virus HBV mouse models Microbiology QR1-502
spellingShingle	adeno-associated virus anti-viral gene therapy hepatitis B virus HBV mouse models Microbiology QR1-502 Shonisani Wendy Limani Njabulo Mnyandu Abdullah Ely Reubina Wadee Anna Kramvis Patrick Arbuthnot Mohube Betty Maepa In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors
description	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.
format	article
author	Shonisani Wendy Limani Njabulo Mnyandu Abdullah Ely Reubina Wadee Anna Kramvis Patrick Arbuthnot Mohube Betty Maepa
author_facet	Shonisani Wendy Limani Njabulo Mnyandu Abdullah Ely Reubina Wadee Anna Kramvis Patrick Arbuthnot Mohube Betty Maepa
author_sort	Shonisani Wendy Limani
title	In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors
title_short	In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors
title_full	In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors
title_fullStr	In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors
title_full_unstemmed	In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors
title_sort	in vivo modelling of hepatitis b virus subgenotype a1 replication using adeno-associated viral vectors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/689e6cf075b94dd7a793c5b0db69c232
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In Vivo Modelling of Hepatitis B Virus Subgenotype A1 Replication Using Adeno-Associated Viral Vectors

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