Clinical features and viral quasispecies characteristics associated with infection by the hepatitis B virus G145R immune escape mutant

Xue, Yuan; Wang, Mingjie; Yang, Zhitao; Yu, Demin; Han, Yue; Huang, Danqing; Zhang, Donghua; Zhang, Xinxin

doi:10.1038/emi.2017.2

Cited by 20 publications

(18 citation statements)

References 28 publications

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“…Viral haplotype determination is the key step in virus community data analysis. There are several possible approaches for determining virus haplotypes: (1) pair-ended amplicon sequencing with relative long read length [34];…”

Section: Discussionmentioning

confidence: 99%

An integrated software for virus community sequencing data analysis

Wang

Zhang

et al. 2020

BMC Genomics

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Background: A virus community is the spectrum of viral strains populating an infected host, which plays a key role in pathogenesis and therapy response in viral infectious diseases. However automatic and dedicated pipeline for interpreting virus community sequencing data has not been developed yet. Results: We developed Quasispecies Analysis Package (QAP), an integrated software platform to address the problems associated with making biological interpretations from massive viral population sequencing data. QAP provides quantitative insight into virus ecology by first introducing the definition "virus OTU" and supports a wide range of viral community analyses and results visualizations. Various forms of QAP were developed in consideration of broader users, including a command line, a graphical user interface and a web server. Utilities of QAP were thoroughly evaluated with high-throughput sequencing data from hepatitis B virus, hepatitis C virus, influenza virus and human immunodeficiency virus, and the results showed highly accurate viral quasispecies characteristics related to biological phenotypes. Conclusions: QAP provides a complete solution for virus community high throughput sequencing data analysis, and it would facilitate the easy analysis of virus quasispecies in clinical applications.

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Section: Discussionmentioning

confidence: 99%

An integrated software for virus community sequencing data analysis

Wang

Zhang

et al. 2020

BMC Genomics

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“…One hypothesis states that it is associated with mutations in the PreS/S gene, especially the “a” determinant and even the polymerase region . Mutations within the “a” determinant may occur under selective pressure induced by host immunity, antiviral therapy, HBV active or passive immunization . Another hypothesis declares that the coexistence of HBsAg and anti‐HBs is associated with the presence of heterologous subtype‐specific anti‐HBs but not with mutations in the S gene region …”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20] Mutations within the "a" determinant may occur under selective pressure induced by host immunity, antiviral therapy, HBV active or passive immunization. [21][22][23][24] Another hypothesis declares that the coexistence of HBsAg and anti-HBs is associated with the presence of heterologous subtype-specific anti-HBs but not with mutations in the S gene region. 9,12 However, because of the difference of the study population including numbers, races, HBV genotypes, inclusion criteria and the sensitiv- Although, in the first stage of our study, genetic association analysis failed to find loci that would achieve a conservative genome-wide significance threshold after Bonferroni correction (P ≤ .05/58563), the results from gene-based burden analysis of rare variants showed OAS3 were achieved a conservative significance threshold after Bonferroni correction of 6994 genes testing (P ≤ .05/6994).…”

Section: Discussionmentioning

confidence: 99%

Identified OAS3 gene variants associated with coexistence of HBsAg and anti‐HBs in chronic HBV infection

Wang

Fan

et al. 2018

Journal of Viral Hepatitis

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The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-stage study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age- and gender-matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48 cases and 200 controls. Although, in the first stage, a genome-wide association study of 58,563 polymorphism variants in 101 cases and 102 controls found no significant loci (P-value ≤ .05/58563), and neither locus achieved a conservative genome-wide significance threshold (P-value ≤ 5e-08), gene-based burden analysis showed that OAS3 gene rare variants were associated with the coexistence of HBsAg and anti-HBs. (P-value = 4.127e-06 ≤ 0.05/6994). A total of 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a stop-gained rare variant was identified. Fisher's exact test of all 149 cases and 302 controls showed that the rare coding sequence mutations were more frequent in cases vs controls (P-value = 7.299e-09, OR = 17.27, 95% CI [5.01-58.72]). Protein-coding rare variations on the OAS3 gene are associated with the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection in Chinese Han population.

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“…(10) Previous studies have held views that the mutation I126T affects the structure of HBsAg, that M133T is more inclined to appear in HBV occult infection and HCC, (39) and that G145R correlatives with immune escape. (22,40) These views provide some clues for our research. Maternal mutations in these areas that viral particles may not easily enter can cause neonates to lose the ability to assemble or normally secrete HBsAg, even if the viral particles enter them.…”

Section: The Possible Role Of A90v In Intrauterine Transmissionmentioning

confidence: 92%

The possible role of S gene mutations of hepatitis B virus in intrauterine transmission

Feng

Yang

et al. 2020

Preprint

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Background: Many hepatitis B virus (HBV) substances could inevitably enter fetuses and occurred neonatal intrauterine transmission. HBV often occurs mutation, especially S gene, and may lead to different outcomes on intrauterine transmission. We explored the associations between HBV S gene mutations of hepatitis B surface antigen positive (HBsAg-positive) mothers and intrauterine transmission. Methods: A total of 399 HBsAg-positive mothers and neonates were recruited and their general demographic information was collected between June 2011 and July 2013. The mothers with HBV DNA levels ≥ 106 IU/ml were selected, 22 mothers whose neonates occurred HBV intrauterine transmission were in the HBV intrauterine transmission group (GT) and 22 mothers were randomly selected from the remaining controls were in the control group (GC). Maternal whole-genome HBV DNA was extracted, amplified, cloned, and sequenced. Obtained sequences were adjusted, genotyped, and analyzed for mutation rates. A case-control study was designed to analyze the relationship between mutations in the S gene of HBV and intrauterine transmission. Results: Fifty-five neonates were found to have experienced intrauterine transmission (13.78%). Genotype B (4.55%), genotype C (88.64%) and inter-genotype B/C (6.81%) were found in the 44 HBsAg-positive mothers. The mutation rates of the S gene, in both genotypes B (0.58% vs 1.41%, P = 0.040) and C (7.56% vs 14.71%, P＜0.001), were lower in group T than in group C. Missense substitutions such as L84I, P47S, K10Q, A41P, M133L, A60V, and I42T only existed in group C. The mutation rates of G73S, I126T, and I126S in group C were higher (P < 0.001, P < 0.001, P = 0.010). Deletions occurred in the S gene. The occurrence of intrauterine transmission with maternal mutation A90V was higher (P < 0.001). This may have increased the risk of neonatal HBsAg expression (P = 0.022). Conclusions: The HBV S gene mutations of HBsAg-positive mothers may reduce the occurrence of HBV intrauterine transmission. It is possible for HBsAg-positive mothers infected with A90V to develop HBV chronic infection and transmit it to the fetus during pregnancy, resulting in neonatal HBV infection.

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Clinical features and viral quasispecies characteristics associated with infection by the hepatitis B virus G145R immune escape mutant

Cited by 20 publications

References 28 publications

An integrated software for virus community sequencing data analysis

An integrated software for virus community sequencing data analysis

Identified OAS3 gene variants associated with coexistence of HBsAg and anti‐HBs in chronic HBV infection

The possible role of S gene mutations of hepatitis B virus in intrauterine transmission

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