TY - JOUR
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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UR - https://www.ncbi.nlm.nih.gov/pubmed/30121196
U2 - https://doi.org/10.1016/j.antiviral.2018.08.009
DO - https://doi.org/10.1016/j.antiviral.2018.08.009
M3 - Article
C2 - 30121196
SN - 0166-3542
VL - 158
SP - 213
EP - 225
JO - Antiviral Research
JF - Antiviral Research
ER -