Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients

Meike H. van der Ree; Louis Jansen; Matthijs R. A. Welkers; Hendrik W. Reesink; K. Anton Feenstra; Neeltje A. Kootstra

doi:10.1016/j.antiviral.2018.08.009

Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients

Meike H. van der Ree, Louis Jansen, Matthijs R. A. Welkers, Hendrik W. Reesink, K. Anton Feenstra, Neeltje A. Kootstra^*

^*Corresponding author for this work

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Abstract

BACKGROUND: We aimed to identify HBc amino acid differences between subgroups of chronic hepatitis B (CHB) patients.

METHODS: Deep sequencing of HBc was performed in samples of 89 CHB patients (42 HBeAg positive, 47 HBeAg negative). Amino acid types were compared using Sequence Harmony to identify subgroup specific sites between HBeAg-positive and -negative patients, and between patients with combined response and non-response to peginterferon/adefovir combination therapy.

RESULTS: We identified 54 positions in HBc where the frequency of appearing amino acids was significantly different between HBeAg-positive and -negative patients. In HBeAg negative patients, 22 positions in HBc were identified which differed between patients with treatment response and those with non-response. The fraction non-consensus sequence on selected positions was significantly higher in HBeAg-negative patients, and was negatively correlated with HBV DNA and HBsAg levels.

CONCLUSIONS: Sequence Harmony identified a number of amino acid changes associated with HBeAg-status and response to peginterferon/adefovir combination therapy.

Original language	English
Pages (from-to)	213-225
Number of pages	13
Journal	Antiviral research
Volume	158
Early online date	16 Aug 2018
DOIs	https://doi.org/10.1016/j.antiviral.2018.08.009
Publication status	Published - Oct 2018

Funding

Meike H. van der Ree: none; Louis Jansen: none; Matthijs Welkers: none; Hendrik W. Reesink: serves as a consultant for AbbVie, Alnylam, Bristol Myers Squibb, Boehringer Ingelheim, ENYO, Gilead Sciences, Janssen-Cilag, Merck, PRA Health Sciences, Regulus, Roche and R-Pharm and received grant/research support from AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, ENYO, Gilead Sciences, Janssen-Cilag, Merck, PRA Health Sciences, Regulus, Replicor and Roche; K. Anton Feenstra: none; Neeltje A. Kootstra: none. This study was funded by Roche the Netherlands.

Funders	Funder number
Roche

Keywords

Chronic hepatitis B
Deep sequencing
HBeAg status
Hepatitis B virus core protein
Treatment response

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.antiviral.2018.08.009

201808_HBV_AVR_preprintSubmitted manuscript, 1.05 MB
Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patientsFinal published version, 1.46 MBLicence: Article 25fa Dutch Copyright Act

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title = "Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients",

abstract = "BACKGROUND: We aimed to identify HBc amino acid differences between subgroups of chronic hepatitis B (CHB) patients.METHODS: Deep sequencing of HBc was performed in samples of 89 CHB patients (42 HBeAg positive, 47 HBeAg negative). Amino acid types were compared using Sequence Harmony to identify subgroup specific sites between HBeAg-positive and -negative patients, and between patients with combined response and non-response to peginterferon/adefovir combination therapy.RESULTS: We identified 54 positions in HBc where the frequency of appearing amino acids was significantly different between HBeAg-positive and -negative patients. In HBeAg negative patients, 22 positions in HBc were identified which differed between patients with treatment response and those with non-response. The fraction non-consensus sequence on selected positions was significantly higher in HBeAg-negative patients, and was negatively correlated with HBV DNA and HBsAg levels.CONCLUSIONS: Sequence Harmony identified a number of amino acid changes associated with HBeAg-status and response to peginterferon/adefovir combination therapy.",

keywords = "Chronic hepatitis B, Deep sequencing, HBeAg status, Hepatitis B virus core protein, Treatment response",

author = "{van der Ree}, {Meike H.} and Louis Jansen and Welkers, {Matthijs R. A.} and Reesink, {Hendrik W.} and Feenstra, {K. Anton} and Kootstra, {Neeltje A.}",

note = "Copyright {\textcopyright} 2018. Published by Elsevier B.V.",

year = "2018",

month = oct,

doi = "10.1016/j.antiviral.2018.08.009",

language = "English",

volume = "158",

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T1 - Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients

AU - van der Ree, Meike H.

AU - Jansen, Louis

AU - Welkers, Matthijs R. A.

AU - Reesink, Hendrik W.

AU - Feenstra, K. Anton

AU - Kootstra, Neeltje A.

PY - 2018/10

Y1 - 2018/10

N2 - BACKGROUND: We aimed to identify HBc amino acid differences between subgroups of chronic hepatitis B (CHB) patients.METHODS: Deep sequencing of HBc was performed in samples of 89 CHB patients (42 HBeAg positive, 47 HBeAg negative). Amino acid types were compared using Sequence Harmony to identify subgroup specific sites between HBeAg-positive and -negative patients, and between patients with combined response and non-response to peginterferon/adefovir combination therapy.RESULTS: We identified 54 positions in HBc where the frequency of appearing amino acids was significantly different between HBeAg-positive and -negative patients. In HBeAg negative patients, 22 positions in HBc were identified which differed between patients with treatment response and those with non-response. The fraction non-consensus sequence on selected positions was significantly higher in HBeAg-negative patients, and was negatively correlated with HBV DNA and HBsAg levels.CONCLUSIONS: Sequence Harmony identified a number of amino acid changes associated with HBeAg-status and response to peginterferon/adefovir combination therapy.

AB - BACKGROUND: We aimed to identify HBc amino acid differences between subgroups of chronic hepatitis B (CHB) patients.METHODS: Deep sequencing of HBc was performed in samples of 89 CHB patients (42 HBeAg positive, 47 HBeAg negative). Amino acid types were compared using Sequence Harmony to identify subgroup specific sites between HBeAg-positive and -negative patients, and between patients with combined response and non-response to peginterferon/adefovir combination therapy.RESULTS: We identified 54 positions in HBc where the frequency of appearing amino acids was significantly different between HBeAg-positive and -negative patients. In HBeAg negative patients, 22 positions in HBc were identified which differed between patients with treatment response and those with non-response. The fraction non-consensus sequence on selected positions was significantly higher in HBeAg-negative patients, and was negatively correlated with HBV DNA and HBsAg levels.CONCLUSIONS: Sequence Harmony identified a number of amino acid changes associated with HBeAg-status and response to peginterferon/adefovir combination therapy.

KW - Chronic hepatitis B

KW - Deep sequencing

KW - HBeAg status

KW - Hepatitis B virus core protein

KW - Treatment response

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Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients

Abstract

Funding

Keywords

UN SDGs

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