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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
Characteristics and evolutionary history of hepatitis B virus quasi-subgenotype B3 in Southeast Asia
Jianmei Gao1, Rongxia Zuo1, Jinli Wang1
1Institute of Basic and Clinical Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Key Laboratory for Birth Defects and Genetic Diseases, the First People's Hospital of Yunnan Province, Kunming, China.
Insights
Hepatitis B virus (HBV) quasi-subgenotype B3 is prevalent in Southeast Asia. Molecular evolution analysis reveals a steady spread from the 1940s to 1990s, with Yunnan strains potentially being the origin.
Area of Science:
- Virology
- Molecular Evolution
- Public Health
Background:
- Hepatitis B virus (HBV) poses a significant global health challenge.
- Understanding HBV genotypes and subgenotypes is crucial for epidemiology and control.
- Quasi-subgenotype B3 is recognized but requires further characterization in Southeast Asia.
Purpose of the Study:
- To analyze the genetic characteristics of HBV quasi-subgenotype B3.
- To investigate the molecular evolution and epidemiology of HBV quasi-subgenotype B3 in Southeast Asia.
- To identify unique genetic markers of HBV quasi-subgenotype B3.
Main Methods:
- Collection and analysis of 411 HBsAg-positive serum samples from Xishuangbanna, China.
- Whole-genome sequencing of 183 HBV strains.
- Phylogenetic analysis and molecular evolutionary dynamics analysis (Bayesian sky plot).
Main Results:
- 183 full-length HBV genomes were obtained, with 139 of genotype B, 41 of genotype C, and 3 of genotype I.
- 34 genotype B sequences were identified as quasi-subgenotype B3.
- Sixteen unique nucleotide mutations were identified in quasi-subgenotype B3 strains.
- The estimated substitution rate was 5.556-5.660 × 10^-4 substitutions/site/year.
- The most recent common ancestor was estimated between 1847-1945, with Yunnan strains as potential progenitors.
- Bayesian sky plot indicated a steady spread from the 1940s to the 1990s.
Conclusions:
- HBV quasi-subgenotype B3 is prevalent in Southeast Asia.
- Molecular evolution analysis supports a steady spread and potential Yunnan origin.
- The identified unique mutations are rare, suggesting current vaccines and antivirals may be effective.
Abstract:
To analyze the hepatitis B virus (HBV) quasi-subgenotype B3 characters and molecular evolution in Southeast Asia, 411 serum samples with HBsAg positive were collected from Xishuangbanna, China. After DNA extraction, PCR amplification and sequencing, a total of 183 HBV full-length genomes were obtained. Phylogenetic analysis showed 139 stains (76.0%) were genotype B, 41 strains were genotype C (22.4%) and 3 strains were genotype I (1.6%). Among genotype B, 34 sequences were identified as quasi-subgenotype B3. Quasi-subgenotype B3 sequences from this study and quasi-subgenotype B3 sequences from the GenBank (total of 141 complete genome sequences) were grouped into quasi-subgenotype B3 (B3, formerly B5, Chinese B6 and B7-9). Sixteen peculiar nucleotides distributed in quasi-subgenotype B3 were identified, which were differ from B1, B2, B4 and B5(formerly B6) (nt93 T, nt100C, nt355 G, nt843 T, nt861C, nt912C, nt929 T, nt930 G, nt1023 T, nt1041 T, nt2651C, nt2693 T, nt2970C, nt3054A, nt3087A and nt3171 G). Then Evolutionary dynamics analysis of HBV quasi-subgenotype B3 was performed. The mean rate of nucleotide substitution for HBV quasi-subgenotype B3 was estimated to be around 5.556-5.660 × 10-4 substitutions/site/year. Estimated time to most recent ancestor of quasi-subgenotype B3 was around the 1847-1945(95%HPD), and Yunnan strains might be the parental strains. The Bayesian sky plot showed a steady spreading of HBV quasi-genotype B3 from early of 1940s to 90 s. In summary, HBV quasi-subgenotype B3 infection is prevalent in Southeast Asia based on the current reports and still with a high prevalence rate based on the evolutionary dynamics analysis. Current vaccine and nucleotide analogues might have effective prevention and treatment for HBV quasi-subgenotype B3 based on the rare clinically relevant mutation sites included in quasi-subgenotype B3.
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