Whole genome deep sequencing analysis of viral quasispecies diversity and evolution in HBeAg seroconverters

Lin, Su-Ru; Yang, Ting‐Hua; Peng, Cheng‐Yuan; Lin, You‐Yu; Dai, Chia‐Yen; Wang, Hurng‐Yi; Su, Tung‐Hung; Tseng, Tai‐Chung; Liu, I-Jung; Cheng, Huei‐Ru; Shen, Yueh-Chi; Wu, Fang–Jing; Liu, Chun‐Jen; Chen, Ding‐Shinn; Chen, Pei‐Jer; Yang, Hsiao-Ching

doi:10.1016/j.jhepr.2021.100254

Cited by 12 publications

(9 citation statements)

References 40 publications

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“…Statistically significant associations were found between high numbers of LFV and mild cases. It has been suggested in the literature for other viruses that within-host diversity can be driven by host selection pressure [68,69]. In contrast to our results where more LFV were observed in mild cases, Simon et al observed higher diversity within the PA, HA and NA segments in severe cases compared to mild cases [18].…”

Section: Discussioncontrasting

confidence: 99%

A general approach to identify low-frequency variants within influenza samples collected during routine surveillance

et al. 2022

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Influenza viruses exhibit considerable diversity between hosts. Additionally, different quasispecies can be found within the same host. High-throughput sequencing technologies can be used to sequence a patient-derived virus population at sufficient depths to identify low-frequency variants (LFV) present in a quasispecies, but many challenges remain for reliable LFV detection because of experimental errors introduced during sample preparation and sequencing. High genomic copy numbers and extensive sequencing depths are required to differentiate false positive from real LFV, especially at low allelic frequencies (AFs). This study proposes a general approach for identifying LFV in patient-derived samples obtained during routine surveillance. Firstly, validated thresholds were determined for LFV detection, whilst balancing both the cost and feasibility of reliable LFV detection in clinical samples. Using a genetically well-defined population of influenza A viruses, thresholds of at least 104 genomes per microlitre and AF of ≥5 % were established as detection limits. Secondly, a subset of 59 retained influenza A (H3N2) samples from the 2016–2017 Belgian influenza season was composed. Thirdly, as a proof of concept for the added value of LFV for routine influenza monitoring, potential associations between patient data and whole genome sequencing data were investigated. A significant association was found between a high prevalence of LFV and disease severity. This study provides a general methodology for influenza LFV detection, which can also be adopted by other national influenza reference centres and for other viruses such as SARS-CoV-2. Additionally, this study suggests that the current relevance of LFV for routine influenza surveillance programmes might be undervalued.

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Section: Discussioncontrasting

confidence: 99%

A general approach to identify low-frequency variants within influenza samples collected during routine surveillance

et al. 2022

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“…HBV infection is a dynamic process and the positivity of serologic markers are subjected to change according to the infection status. HBeAg is considered as a marker of active infection,17 the loss of HBeAg or the conversion to HBeAb is an indicator of clinical remission and is associated with slower disease progression, lower incidence of liver cirrhosis and increased possibility of HBsAg seroconversion 18,19. In our recipients with HBsAg seroconversion, the positive cases for HBeAg decreased over time, indicating a potential role of HBeAg as a predictive marker for seroconversion in paediatric recipients who experience de novo HBV infection.…”

mentioning

confidence: 76%

HBsAg seroconversion in de novo hepatitis B virus‐infected paediatric liver transplant recipients with anti‐viral therapy

Dong

Song

Sun

et al. 2022

Journal of Viral Hepatitis

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We investigated the clinical characteristics and therapeutic strategies for paediatric liver transplant (PLT) recipients who experienced de novo hepatitis B virus infection and the features of HBsAg seroconversion. A total of 821 PLT were performed in HBV-free recipients between January 2013 and January 2019 in Paediatric Organ Transplant Center, Tianjin First Central Hospital. Twenty-one recipients developed de novo HBV infection, the clinical data were analysed. The overall incidence of de novo HBV infection was 2.5%. Only one recipient received an HBcAb-negative graft, 20 recipients received HBcAb-positive grafts. The incidence of de novo HBV infection in HBcAb-negative and HBcAb-positive graft recipients were 0.2% and 6.3%, respectively. Fifteen de novo HBV-infected recipients showed HBsAg seroconversion, the incidence of HBsAg seroconversion was 71.4%. The median time from the diagnosis of de novo HBV infection to HBsAg seroconversion was 15 (1, 73) months.Recipients with hepatitis B surface antigen (HBsAg) titre <1000 IU/L and negative hepatitis B e antigen (HBeAg) at the time of de novo HBV infection diagnosis were more likely to achieve HBsAg seroconversion. Nucleotide analogues were effective in treating recipients with de novo HBV infection. De novo HBV infection does not impact liver graft function as well as recipient and graft survival rate. De novo HBV infection does not impact PLT recipient outcomes under close monitoring and appropriate treatment. High incidence of HBsAg seroconversion can be achieved after anti-viral therapy.

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“…20 While most iSNVs studies were focused on RNA viruses, only limited reports have described the existence of iSNVs in DNA viruses such as hepatitis B virus (HBV), posttransfusion hepatitis TT virus, and human polyomavirus JC virus, and so forth. [27][28][29] However, the dynamic features of DNA viruses and the clinical impacts are not well understood. Using deep sequencing, we analyzed and compared iSNVs in original swab samples and cell isolated viruses of a cohort of adenovirus patients.…”

Section: Discussionmentioning

confidence: 99%

“…Deep sequencing of original viral‐positive samples could directly demonstrate in vivo host adaptation and provide novel insights into viral evolutionary dynamics 20 . While most iSNVs studies were focused on RNA viruses, only limited reports have described the existence of iSNVs in DNA viruses such as hepatitis B virus (HBV), posttransfusion hepatitis TT virus, and human polyomavirus JC virus, and so forth 27–29 . However, the dynamic features of DNA viruses and the clinical impacts are not well understood.…”

Section: Discussionmentioning

confidence: 99%

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Intrahost variation and evolutionary dynamics of adenoviruses correlate to neutrophils in infected patients

Huo

Yan

Guo

et al. 2022

Journal of Medical Virology

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With deep sequencing of virus genomes within the hosts, intrahost single nucleotide variations (iSNVs) have been used for analyses of virus genome variation and evolution, which is indicated to correlate with viral pathogenesis and disease severity. Little is known about the features of iSNVs among DNA viruses. We performed the epidemiological and laboratory investigation of one outbreak of adenovirus. The whole genomes of viruses in both original oral swabs and cellcultured virus isolates were deeply sequenced. We identified 737 iSNVs in the viral genomes sequenced from original samples and 46 viral iSNVs in cell-cultured isolates, with 33 iSNVs shared by original samples and cultured isolates. Meanwhile, we found these 33 iSNVs were shared by different patients, among which, three hot spot areas 6367−6401, 9213−9247, and 10 584−10 606 within the functional genes of the adenovirus genome were found. Notably, the substitution rates of iSNVs were closely correlated with the clinical and immune indicators of the patients. Especially a positive correlation to neutrophils was found, indicating a predictable biomarker of iSNV dynamics. Our findings demonstrated the neutrophil-correlated dynamic evolution features of the iSNVs within adenoviruses, which indicates a virus−host interaction during human infection of a DNA virus.

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Whole genome deep sequencing analysis of viral quasispecies diversity and evolution in HBeAg seroconverters

Cited by 12 publications

References 40 publications

A general approach to identify low-frequency variants within influenza samples collected during routine surveillance

A general approach to identify low-frequency variants within influenza samples collected during routine surveillance

HBsAg seroconversion in de novo hepatitis B virus‐infected paediatric liver transplant recipients with anti‐viral therapy

Intrahost variation and evolutionary dynamics of adenoviruses correlate to neutrophils in infected patients

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