In vitro replication phenotype of a novel (-1G) hepatitis B virus variant associated with HIV co-infection

Liza M Cabuang, T Shaw, Margaret Littlejohn, Danni Colledge, Vitini Sozzi, Sally Soppe, N Warner, Alex J V Thompson, Scott Preiss, Natasha Lam, Renae B Walsh, Sharon R Lewin, Chloe L Thio, Gail Matthews, Stephen Locarnini, Peter Revill

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Abstract

The -1G mutant HBV is more prevalent in individuals co-infected with HIV/HBV than in individuals infected with HBV alone and in some cases is the dominant virus in circulation. This mutant is created by the deletion of a dGMP (-1G) from the guanine rich homopolymer sequence located at nts 2,085-2,090 (numbering from EcoRI site as position 1) in the HBV core gene. This deletion causes a frameshift generating a premature stop codon at 64Asn in the HBV core gene (codon 93 in the precore gene), that truncates the precore protein, precursor of the secreted hepatitis B e antigen (HBeAg), and the core protein which forms the viral nucleocapsid. However, the replication phenotype of the -1G mutant HBV is unknown. An in vitro cell culture model in which hepatoma cells were transiently transfected with infectious cDNAs was used to show that the -1G mutant HBV is incapable of autonomous replication and, as expected, replication was restored to wild-type (wt) levels by supplying HBV core protein in trans. Although the -1G mutation had no deleterious effect on intracellular HBV-DNA levels, high levels of -1G mutant HBV relative to wt HBV reduced virus secretion and HBeAg secretion relative to empty vector controls. Importantly, the -1G mutant HBV also caused intracellular retention of truncated precore protein in the endoplasmic reticulum (ER) and Golgi apparatus. Together, these effects may be contributing to the increased pathology observed in the setting of HIV/HBV co-infection. ? 2012 Wiley Periodicals, Inc..
Original languageEnglish
Pages (from-to)1166 - 1176
Number of pages11
JournalJournal of Medical Virology
Volume84
Issue number8
DOIs
Publication statusPublished - 2012

Cite this

Cabuang, Liza M ; Shaw, T ; Littlejohn, Margaret ; Colledge, Danni ; Sozzi, Vitini ; Soppe, Sally ; Warner, N ; Thompson, Alex J V ; Preiss, Scott ; Lam, Natasha ; Walsh, Renae B ; Lewin, Sharon R ; Thio, Chloe L ; Matthews, Gail ; Locarnini, Stephen ; Revill, Peter. / In vitro replication phenotype of a novel (-1G) hepatitis B virus variant associated with HIV co-infection. In: Journal of Medical Virology. 2012 ; Vol. 84, No. 8. pp. 1166 - 1176.
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title = "In vitro replication phenotype of a novel (-1G) hepatitis B virus variant associated with HIV co-infection",
abstract = "The -1G mutant HBV is more prevalent in individuals co-infected with HIV/HBV than in individuals infected with HBV alone and in some cases is the dominant virus in circulation. This mutant is created by the deletion of a dGMP (-1G) from the guanine rich homopolymer sequence located at nts 2,085-2,090 (numbering from EcoRI site as position 1) in the HBV core gene. This deletion causes a frameshift generating a premature stop codon at 64Asn in the HBV core gene (codon 93 in the precore gene), that truncates the precore protein, precursor of the secreted hepatitis B e antigen (HBeAg), and the core protein which forms the viral nucleocapsid. However, the replication phenotype of the -1G mutant HBV is unknown. An in vitro cell culture model in which hepatoma cells were transiently transfected with infectious cDNAs was used to show that the -1G mutant HBV is incapable of autonomous replication and, as expected, replication was restored to wild-type (wt) levels by supplying HBV core protein in trans. Although the -1G mutation had no deleterious effect on intracellular HBV-DNA levels, high levels of -1G mutant HBV relative to wt HBV reduced virus secretion and HBeAg secretion relative to empty vector controls. Importantly, the -1G mutant HBV also caused intracellular retention of truncated precore protein in the endoplasmic reticulum (ER) and Golgi apparatus. Together, these effects may be contributing to the increased pathology observed in the setting of HIV/HBV co-infection. ? 2012 Wiley Periodicals, Inc..",
author = "Cabuang, {Liza M} and T Shaw and Margaret Littlejohn and Danni Colledge and Vitini Sozzi and Sally Soppe and N Warner and Thompson, {Alex J V} and Scott Preiss and Natasha Lam and Walsh, {Renae B} and Lewin, {Sharon R} and Thio, {Chloe L} and Gail Matthews and Stephen Locarnini and Peter Revill",
year = "2012",
doi = "10.1002/jmv.23328",
language = "English",
volume = "84",
pages = "1166 -- 1176",
journal = "Journal of Medical Virology",
issn = "0146-6615",
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Cabuang, LM, Shaw, T, Littlejohn, M, Colledge, D, Sozzi, V, Soppe, S, Warner, N, Thompson, AJV, Preiss, S, Lam, N, Walsh, RB, Lewin, SR, Thio, CL, Matthews, G, Locarnini, S & Revill, P 2012, 'In vitro replication phenotype of a novel (-1G) hepatitis B virus variant associated with HIV co-infection', Journal of Medical Virology, vol. 84, no. 8, pp. 1166 - 1176. https://doi.org/10.1002/jmv.23328

In vitro replication phenotype of a novel (-1G) hepatitis B virus variant associated with HIV co-infection. / Cabuang, Liza M; Shaw, T; Littlejohn, Margaret; Colledge, Danni; Sozzi, Vitini; Soppe, Sally; Warner, N; Thompson, Alex J V; Preiss, Scott; Lam, Natasha; Walsh, Renae B; Lewin, Sharon R; Thio, Chloe L; Matthews, Gail; Locarnini, Stephen; Revill, Peter.

In: Journal of Medical Virology, Vol. 84, No. 8, 2012, p. 1166 - 1176.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - In vitro replication phenotype of a novel (-1G) hepatitis B virus variant associated with HIV co-infection

AU - Cabuang, Liza M

AU - Shaw, T

AU - Littlejohn, Margaret

AU - Colledge, Danni

AU - Sozzi, Vitini

AU - Soppe, Sally

AU - Warner, N

AU - Thompson, Alex J V

AU - Preiss, Scott

AU - Lam, Natasha

AU - Walsh, Renae B

AU - Lewin, Sharon R

AU - Thio, Chloe L

AU - Matthews, Gail

AU - Locarnini, Stephen

AU - Revill, Peter

PY - 2012

Y1 - 2012

N2 - The -1G mutant HBV is more prevalent in individuals co-infected with HIV/HBV than in individuals infected with HBV alone and in some cases is the dominant virus in circulation. This mutant is created by the deletion of a dGMP (-1G) from the guanine rich homopolymer sequence located at nts 2,085-2,090 (numbering from EcoRI site as position 1) in the HBV core gene. This deletion causes a frameshift generating a premature stop codon at 64Asn in the HBV core gene (codon 93 in the precore gene), that truncates the precore protein, precursor of the secreted hepatitis B e antigen (HBeAg), and the core protein which forms the viral nucleocapsid. However, the replication phenotype of the -1G mutant HBV is unknown. An in vitro cell culture model in which hepatoma cells were transiently transfected with infectious cDNAs was used to show that the -1G mutant HBV is incapable of autonomous replication and, as expected, replication was restored to wild-type (wt) levels by supplying HBV core protein in trans. Although the -1G mutation had no deleterious effect on intracellular HBV-DNA levels, high levels of -1G mutant HBV relative to wt HBV reduced virus secretion and HBeAg secretion relative to empty vector controls. Importantly, the -1G mutant HBV also caused intracellular retention of truncated precore protein in the endoplasmic reticulum (ER) and Golgi apparatus. Together, these effects may be contributing to the increased pathology observed in the setting of HIV/HBV co-infection. ? 2012 Wiley Periodicals, Inc..

AB - The -1G mutant HBV is more prevalent in individuals co-infected with HIV/HBV than in individuals infected with HBV alone and in some cases is the dominant virus in circulation. This mutant is created by the deletion of a dGMP (-1G) from the guanine rich homopolymer sequence located at nts 2,085-2,090 (numbering from EcoRI site as position 1) in the HBV core gene. This deletion causes a frameshift generating a premature stop codon at 64Asn in the HBV core gene (codon 93 in the precore gene), that truncates the precore protein, precursor of the secreted hepatitis B e antigen (HBeAg), and the core protein which forms the viral nucleocapsid. However, the replication phenotype of the -1G mutant HBV is unknown. An in vitro cell culture model in which hepatoma cells were transiently transfected with infectious cDNAs was used to show that the -1G mutant HBV is incapable of autonomous replication and, as expected, replication was restored to wild-type (wt) levels by supplying HBV core protein in trans. Although the -1G mutation had no deleterious effect on intracellular HBV-DNA levels, high levels of -1G mutant HBV relative to wt HBV reduced virus secretion and HBeAg secretion relative to empty vector controls. Importantly, the -1G mutant HBV also caused intracellular retention of truncated precore protein in the endoplasmic reticulum (ER) and Golgi apparatus. Together, these effects may be contributing to the increased pathology observed in the setting of HIV/HBV co-infection. ? 2012 Wiley Periodicals, Inc..

UR - http://onlinelibrary.wiley.com/doi/10.1002/jmv.23328/pdf

U2 - 10.1002/jmv.23328

DO - 10.1002/jmv.23328

M3 - Article

VL - 84

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EP - 1176

JO - Journal of Medical Virology

JF - Journal of Medical Virology

SN - 0146-6615

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