Complete genome analysis of hepatitis B virus in Qinghai-Tibet plateau: the geographical distribution, genetic diversity, and co-existence of HBsAg and anti-HBs antibodies

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Abstract

Background

The genetic variation and origin of Hepatitis B Virus (HBV) in Qinghai-Tibet Plateau were poorly studied. The coexistence of HBsAg and anti-HBs has been described as a puzzle and has never been reported in the indigenous population or in recombinant HBV sequences. This study aimed to report geographical distribution, genetic variability and seroepidemiology of HBV in southwest China.

Methods

During 2014–2017, 1263 HBsAg positive serum were identified and 183 complete genome sequences were obtained. Serum samples were collected from community-based populations by a multistage random sampling method. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then recombination, genetic variability, and serological analysis were performed.

Results

(1) Of the 1263 HBsAg positive serum samples, there were significant differences between the distribution of seromarkers in Tibet and Qinghai. (2) Of 183 complete genome sequences, there were 130 HBV/CD1 (71.0%), 49 HBV/CD2 (26.8%) and four HBV/C2 isolates (2.2%). Serotype ayw2 (96.1%) was the main serological subtype. (3) Several nucleotide mutations were dramatically different in CD1 and CD2 sequences. Clinical prognosis-related genetic variations such as nucleotide mutation T1762/A1764 (27.93%), A2189C (12.85%), G1613A (8.94%), T1753C (8.38%), T53C (4.47%) T3098C (1.68%) and PreS deletion (2.23%) were detected in CD recombinants. (4) From the inner land of China to the northeast boundary of India, different geographical distributions between CD1 and CD2 were identified. (5) Twenty-seven (2.14%) HBsAg/HBsAb coexistence serum samples were identified. S protein amino acid mutation and PreS deletion were with significant differences between HBsAg/HBsAb coexistence group and control group.

Conclusions

HBV/CD may have a mixed China and South Asia origin. Based on genetic variations, the clinical prognosis of CD recombinant seems more temperate than genotype C strains in China. The HBsAg/HBsAb coexistence is a result of both PreS deletion and aa variation in S protein. Several unique mutations were frequently detected in HBV/CD isolates, which could potentially influence the clinical prognosis.

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Most cited references 40

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Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination.

Xiaofeng Liang, Shengli Bi, Weizhong Yang … (2009)

To determine the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc) in a representative population in China 14 years after introduction of hepatitis B vaccination of infants. National serosurvey, with participants selected by multi-stage random sampling. Demographics and hepatitis B vaccination history collected by questionnaire and review of vaccination records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA. The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese population aged 1-59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg prevalence was greatly diminished among those age <15 years compared to that found in the 1992 national serosurvey, and among children age <5 years was only 1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with vaccination among all age groups. HBsAg risk in adults was associated with male sex, Western region, and certain ethnic groups and occupations while risk in children included birth at home or smaller hospitals, older age, and certain ethnic groups (Zhuang and other). China has already reached the national goal of reducing HBsAg prevalence to less than 1% among children under 5 years and has prevented an estimated 16-20 million HBV carriers through hepatitis B vaccination of infants. Immunization program should be further strengthened to reach those remaining at highest risk.

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Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and CMV UL130 originate from chemokines

Maja Malkowska, Katarzyna Kokoszynska, Magdalena Dymecka … (2013)

Herpesviridae is a large family of DNA viruses divided into three subfamilies: Alpha-, Beta- and Gammaherpesvirinae. The process of herpesvirus transmission is mediated by a range of proteins, one of which is glycoprotein L (gL). Based on our analysis of the solved structures of HSV2 and EBV gH/gL complexes, we propose that Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and Betaherpesvirinae UL130 originate from chemokines. Herpes simplex virus type 2 gL and human cytomegalovirus homolog (UL130) adopt a novel C chemokine-like fold, while Epstein-Barr virus gL mimics a CC chemokine structure. Hence, it is possible that gL interface with specific chemokine receptors during the transmission of Herpesviridae. We conclude that the further understanding of the function of viral chemokine-like proteins in Herpesviridae infection may lead to development of novel prophylactic and therapeutic treatment.

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Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants.

Chih-Lin Lin, Jia-Horng Kao (2017)

Molecular epidemiologic studies reveal remarkable differences in the geographical distribution of hepatitis B virus (HBV) genotypes. The frequency of mutants among HBV genotypes also varies. The role of HBV genotypes/mutants in the pathogenesis of HBV infection and natural history of HBV infection has been extensively investigated. The distribution of HBV genotypes in acute hepatitis B patients reflects the predominant genotypes in a given geographic area. In chronic hepatitis B patients, genotype C and D have a higher frequency of basal core promoter A1762T/G1764A mutations than genotype A and B. HBV genotypes C, D and F carry a higher lifetime risk of cirrhosis and HCC development than genotype A and B. HBV pre-S/S gene mutations were associated with immune escape of hepatitis B immunoglobulin or vaccine-induced immunity. Mutations in the pre-S, core promoter and X regions correlate with an increased risk of cirrhosis and HCC. In summary, HBV genotypes and mutants are associated with the disease progression and long-term outcome of HBV infection. They may serve as viral genetic markers for risk stratification of chronic hepatitis B patients in clinical practice.

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Author and article information

Contributors

Shengli Bi:

ORCID: http://orcid.org/0000-0002-0380-5790

bisl@ivdc.chinacdc.cn

Journal

Journal ID (nlm-ta): Virol J

Journal ID (iso-abbrev): Virol. J

Title: Virology Journal

Publisher: BioMed Central (London )

ISSN (Electronic): 1743-422X

Publication date (Electronic): 12 June 2020

Publication date PMC-release: 12 June 2020

Publication date Collection: 2020

Volume: 17

Electronic Location Identifier: 75

Affiliations

[1 ]GRID grid.198530.6, ISNI 0000 0000 8803 2373, NHC Key Laboratory of Medical Virology and Viral Diseases, , National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, ; Changbai Rd 155#, Changping District, Beijing, China

[2 ]GRID grid.198530.6, ISNI 0000 0000 8803 2373, Department of Infectious Disease, , Tianjin Center for Disease Control and Prevention, ; Tianjin, People’s Republic of China

[3 ]GRID grid.198530.6, ISNI 0000 0000 8803 2373, National Immunization Program, , Chinese Center for Disease Control and Prevention, ; Beijing, People’s Republic of China

[4 ]GRID grid.198530.6, ISNI 0000 0000 8803 2373, Chinese Center for Disease Control and Prevention, ; Beijing, People’s Republic of China

Author information

Shengli Bi http://orcid.org/0000-0002-0380-5790

Article

Publisher ID: 1350

DOI: 10.1186/s12985-020-01350-w

PMC ID: 7291583

SO-VID: c11a2b9c-938a-4e15-9d48-aaa74bec16a2

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 2 January 2020

Date accepted : 3 June 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100013076, National Major Science and Technology Projects of China;

Award ID: 2012ZX10002-001-005-001

Award ID: 2012ZX10002-001-005

Award Recipient : Shengli Bi

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ScienceOpen disciplines: Microbiology & Virology

Keywords: hepatitis b virus,mutation/mutation rate,recombination,hepatitis b surface antigen,antibody to hbsag

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ScienceOpen disciplines: Microbiology & Virology

Keywords: hepatitis b virus, mutation/mutation rate, recombination, hepatitis b surface antigen, antibody to hbsag

Complete genome analysis of hepatitis B virus in Qinghai-Tibet plateau: the geographical distribution, genetic diversity, and co-existence of HBsAg and anti-HBs antibodies

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Most cited references 40

Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination.

Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and CMV UL130 originate from chemokines

Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants.

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