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Conference Paper: Sequence variations of full-length hepatitis B virus genomes in Chinese patients with HBsAg-negative hepatitis B infection
Title | Sequence variations of full-length hepatitis B virus genomes in Chinese patients with HBsAg-negative hepatitis B infection |
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Authors | |
Issue Date | 2015 |
Publisher | Spandidos Publications. |
Citation | The 20th World Congress on Advances in Oncology and 18th International Symposium on Molecular Medicine, Athens, Greece, 8-10 October 2015. In Conference Proceedings, 2015, v. 36 suppl. 1 , p. S21 How to Cite? |
Abstract | The underlying mechanism of HBsAg-negative hepatitis B virus (HBV) infection is notoriously difficult to elucidate because of the extremely low DNA levels which define the condition. We used a highly efficient amplification method to overcome this obstacle and achieved our aim which was to identify specific mutations or sequence variations associated with this entity. In this study, a total of 185 sera and 60 liver biopsies from HBsAg-negative, HBV DNA-positive subjects or known chronic hepatitis B (CHB) subjects with HBsAg seroclearance were amplified by rolling circle amplification followed by full-length HBV genome sequencing. Eleven HBsAg-positive CHB subjects were included as controls. The effects of pivotal mutations identified on regulatory regions on promoter activities were analyzed. A total of 22 and 11 full-length HBV genomes were amplified from HBsAg-negative and control subjects respectively. HBV genotype C was the dominant strain. A higher mutation frequency was observed in HBsAg-negative subjects than controls, irrespective of genotype. The nucleotide diversity over the entire HBV genome was significantly higher in HBsAg-negative subjects compared with controls (p = 0.008) and compared with 49 reference sequences from CHB patients (p = 0.025). In addition, HBsAg-negative subjects had significantly higher amino acid substitutions in the four viral genes than controls (all p < 0.001). Many mutations were uniquely found in HBsAg-negative subjects, including deletions in promoter regions (13.6%), abolishment of pre-S2/S start codon (18.2%), disruption of pre-S2/S mRNA splicing site (4.5%), nucleotide duplications (9.1%), and missense mutations in “α” determinant region, contributing to defects in HBsAg production. Taken together, these data suggest an accumulation of multiple mutations constraining viral transcriptional activities contribute to HBsAg-negativity in HBV infection. This study was supported by General Research Fund (HKU 782809) |
Description | Oral Presentation |
Persistent Identifier | http://hdl.handle.net/10722/229854 |
DC Field | Value | Language |
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dc.contributor.author | Huang, FY | - |
dc.contributor.author | Wong, DKH | - |
dc.contributor.author | Seto, WKW | - |
dc.contributor.author | Zhang, AY | - |
dc.contributor.author | Lee, CK | - |
dc.contributor.author | Lin, CK | - |
dc.contributor.author | Fung, JYY | - |
dc.contributor.author | Lai, CL | - |
dc.contributor.author | Yuen, RMF | - |
dc.date.accessioned | 2016-08-23T14:13:39Z | - |
dc.date.available | 2016-08-23T14:13:39Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | The 20th World Congress on Advances in Oncology and 18th International Symposium on Molecular Medicine, Athens, Greece, 8-10 October 2015. In Conference Proceedings, 2015, v. 36 suppl. 1 , p. S21 | - |
dc.identifier.uri | http://hdl.handle.net/10722/229854 | - |
dc.description | Oral Presentation | - |
dc.description.abstract | The underlying mechanism of HBsAg-negative hepatitis B virus (HBV) infection is notoriously difficult to elucidate because of the extremely low DNA levels which define the condition. We used a highly efficient amplification method to overcome this obstacle and achieved our aim which was to identify specific mutations or sequence variations associated with this entity. In this study, a total of 185 sera and 60 liver biopsies from HBsAg-negative, HBV DNA-positive subjects or known chronic hepatitis B (CHB) subjects with HBsAg seroclearance were amplified by rolling circle amplification followed by full-length HBV genome sequencing. Eleven HBsAg-positive CHB subjects were included as controls. The effects of pivotal mutations identified on regulatory regions on promoter activities were analyzed. A total of 22 and 11 full-length HBV genomes were amplified from HBsAg-negative and control subjects respectively. HBV genotype C was the dominant strain. A higher mutation frequency was observed in HBsAg-negative subjects than controls, irrespective of genotype. The nucleotide diversity over the entire HBV genome was significantly higher in HBsAg-negative subjects compared with controls (p = 0.008) and compared with 49 reference sequences from CHB patients (p = 0.025). In addition, HBsAg-negative subjects had significantly higher amino acid substitutions in the four viral genes than controls (all p < 0.001). Many mutations were uniquely found in HBsAg-negative subjects, including deletions in promoter regions (13.6%), abolishment of pre-S2/S start codon (18.2%), disruption of pre-S2/S mRNA splicing site (4.5%), nucleotide duplications (9.1%), and missense mutations in “α” determinant region, contributing to defects in HBsAg production. Taken together, these data suggest an accumulation of multiple mutations constraining viral transcriptional activities contribute to HBsAg-negativity in HBV infection. This study was supported by General Research Fund (HKU 782809) | - |
dc.language | eng | - |
dc.publisher | Spandidos Publications. | - |
dc.relation.ispartof | 20th World Congress on Advances in Oncology & 18th International Symposium on Molecular Medicine Proceedings | - |
dc.title | Sequence variations of full-length hepatitis B virus genomes in Chinese patients with HBsAg-negative hepatitis B infection | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Huang, FY: fungyu@hkucc.hku.hk | - |
dc.identifier.email | Wong, DKH: danywong@hku.hk | - |
dc.identifier.email | Seto, WKW: wkseto@hku.hk | - |
dc.identifier.email | Fung, JYY: jfung@hkucc.hku.hk | - |
dc.identifier.email | Lai, CL: hrmelcl@hkucc.hku.hk | - |
dc.identifier.email | Yuen, RMF: mfyuen@hku.hk | - |
dc.identifier.authority | Wong, DKH=rp00492 | - |
dc.identifier.authority | Seto, WKW=rp01659 | - |
dc.identifier.authority | Fung, JYY=rp00518 | - |
dc.identifier.authority | Lai, CL=rp00314 | - |
dc.identifier.authority | Yuen, RMF=rp00479 | - |
dc.identifier.hkuros | 262410 | - |
dc.identifier.volume | 36 | - |
dc.identifier.issue | suppl. 1 | - |
dc.identifier.spage | S21 | - |
dc.identifier.epage | S21 | - |
dc.publisher.place | London | - |