Reconstruction of the origin and dispersal of the worldwide dominant Hepatitis B Virus subgenotype D1

Funding Information: N.S.T. and P.L. were supported by the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement number 278433-PREDEMICS. The research leading to these results has received funding from the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422 - ReservoirDOCS). MT is a PhD fellow at the Research Foundation Flanders (FWO, Belgium, grant number 1S47118N). A.-C.P.-P. was supported by European Funds through grant 'Bio-Molecular and Epidemiological Surveillance of HIV Transmitted Drug Resistance, Hepatitis Co- Infections and Ongoing Transmission Patterns in Europe' (BEST HOPE) (project funded through HIVERA: Harmonizing Integrating Vitalizing European Research on HIV/Aids, grant 249697); by Fundação para a Cieñcia e Tecnologia for funds to GHTMUID/ Multi/04413/2013; by the Migrant HIV project (financed by FCT: PTDC/DTP-EPI/7066/2014; and by Gilead Ǵenese HIVLatePresenters. B.V. was supported by a postdoctoral grant (12U7121N) of the FWO (Fonds Wetenschappelijk Onderzoek - Vlaanderen). G.B. acknowledges support from the Interne Fondsen KU Leuven/ Internal Funds KU Leuven under grant agreement C14/18/094 and the Research Foundation - Flanders ('Fonds voor Wetenschappelijk Onderzoek - Vlaanderen', G0E1420N, G098321N). This work was supported by the Bijzonder Onderzoeksfonds KU Leuven (BOF) No. OT/14/115. This work was supported by public grants. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022 The Author(s).Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV-D1 is the dominant subgenotype in the Mediterranean basin, Eastern Europe, and Asia. However, little is currently known about its evolutionary history and spatio-temporal dynamics. We use Bayesian phylodynamic inference to investigate the temporal history of HBV-D1, for which we calibrate the molecular clock using ancient sequences, and reconstruct the viral global spatial dynamics based, for the first time, on full-length publicly available HBV-D1 genomes from a wide range of sampling dates. We pinpoint the origin of HBV subgenotype D1 before the current era (BCE) in Turkey/Anatolia. The spatial reconstructions reveal global viral transmission with a high degree of mixing. By combining modern-day and ancient sequences, we ensure sufficient temporal signal in HBV-D1 data to enable Bayesian phylodynamic inference using a molecular clock for time calibration. Our results shed light on the worldwide HBV-D1 epidemics and suggest that this originally Middle Eastern virus significantly affects more distant countries, such as those in mainland Europe.publishersversionpublishe

Elimination of Viral Hepatitis and an Update on Blood Safety Technology

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Novel Hepatitis B virus Subgenotype A8 and Quasi-subgenotype D12 in African-Belgian chronic carriers

BACKGROUND: Hepatitis B virus (HBV) is a public health threatening virus and is classified into more than eight genotypes and more than forty subgenotypes. OBJECTIVES: To characterize and propose novel strains assigned as A8 and D12. METHODS: Four out of 133 HBV complete genome sequences, isolated from Belgian chronic carriers with African origin were phylogenetically analyzed. RESULTS: Phylogenetic analyses of HBV genotypes A and D strains exhibited separate clusters supported by significant bootstrap values. The two genotype A strains isolated from Congolese patients, and two genotype D strains isolated from Ghanaian carriers clustered separately from the other known subgenotypes A (A1-A6 and quasi-subgenotypes) and subgenotypes D (D1-D11). The mean inter-subgenotypic nucleotide divergence over the full-length genome sequence between the novel strains (A8 and D12) and A1-A7 and D1-D11 subgenotypes was higher than 4%. CONCLUSIONS: Phylogenetic analysis of the full-length HBV genome sequences revealed a novel subgenotype and quasi-subgenotype based on the nucleotide divergence and identification of novel amino acids motifs in different ORFs. We identified two strains of the novel subgenotype A8 and two strains of the novel quasi-subgenotype D12. Notably, the analysis demonstrated that the subgenotype A8 strains are a basal lineage that diverged before the other African subgenotypes A.status: Published onlin

Natural disasters pose a challenge for hepatitis elimination in Iran

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How adequate social media management supports the viral Hepatitis elimination program

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Persons with Intellectual Disability: A Potential Reservoir of Invasive Strains of Hepatitis B Virus

Background: A higher prevalence of hepatitis B virus (HBV) infection has been reported in persons with intellectual disability as well as the nurses working in closed institutions compared to the general population. Objectives: In the present study, the serological and molecular markers of HBV infection in individuals with intellectual disability of closed institutions were investigated. Methods: Blood samples were derived from 400 persons with intellectual disability living in six institutions in Tehran and tested for HBsAg and HBcAb. Nested PCR, direct sequencing, and phylogenetic analysis were performed to determine the HBV genotypes and mutational patterns of HBsAg. Also, HBsAb was tested for HBV DNA positive cases. Results: Twenty-eight (7.0%) patients were positive for the HBsAg serological test. Furthermore, six HBV occult cases were identified. In total, out of 41 patients with HBV infection markers, 26 cases were positive for HBV DNA. Of these patients, 15 full-length HBsAg were successfully amplified and sequenced. All strains belonged to genotype D and subtypes ayw2 and ayw3. These 15 isolated strains carried several immune escape mutants in the S genes. Surprisingly, mutations related to antiviral resistance were detected in the overlapped pol genes of strains isolated from naïve-treatment patients. Conclusions: The observed frequency of HBV infection in individuals with intellectual disability was higher than the reported estimation of HBV infection in Iranian blood donors and the general population. All HBV isolates from these patients represented a homogenous genotype and corresponded with other reported strains from Mediterranean countries. The high frequency of immune escape strains, despite vaccination and detection of identical mutational patterns in different genes, might indicate that persons with intellectual disability have shared vaccine-escape and drug-resistant HBV strains.status: Published onlin

Air conditioning system usage and SARS-CoV-2 transmission dynamics in Iran

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Convalescent Plasma against COVID-19: A broad-spectrum therapeutic approach for emerging infectious diseases

In the lack of an effective vaccine and antiviral treatment, convalescent plasma (CP) has been a promising therapeutic approach in past pandemics. Accumulating evidence in the current SARS-CoV-2 pandemic corroborate the safety of CP therapy and preliminary data underlines the potential efficacy. Recently the FDA permitted CP therapy for COVID-19 patients under the emergency use authorization (EUA), albeit additional clinical studies are needed. The imminent threat of a second or even multiple waves of COVID-19, compels health authorities to delineate and calibrate a feasible preparedness algorithm for deploying CP as an immediate therapeutic intervention. The success of preparedness programs depends on the interdisciplinary actions of multiple actors in politics, science and healthcare. In this review, we evaluate the current status of CP therapy for COVID-19 patients and address the challenges that confront the implementation of CP. Finally, we propose a pandemic preparedness framework for future waves of the COVID-19 pandemic and unknown pathogen outbreaks.status: accepte

Exploration of the Ixodes ricinus virosphere unveils an extensive virus diversity including novel coltiviruses and other reoviruses

Recent metagenomics studies have revealed several tick species to host a variety of previously undiscovered RNA viruses. Ixodes ricinus, which is known to be a vector for many viral, bacterial, and protozoan pathogens, is the most prevalent tick species in Europe. For this study, we decided to investigate the virosphere of Belgian I. ricinus ticks. High-throughput sequencing of tick pools collected from six different sampling sites revealed the presence of viruses belonging to many different viral orders and families, including Mononegavirales, Bunyavirales, Partitiviridae, and Reoviridae. Of particular interest was the detection of several new reoviruses, two of which cluster together with members of the genus Coltivirus. This includes a new strain of Eyach virus, a known causative agent of tick-borne encephalitis. All genome segments of this new strain are highly similar to those of previously published Eyach virus genomes, except for the fourth segment, encoding VP4, which is markedly more dissimilar, potentially indicating the occurrence of a genetic reassortment. Further polymerase chain reaction-based screening of over 230 tick pools for 14 selected viruses showed that most viruses could be found in all six sampling sites, indicating the wide spread of these viruses throughout the Belgian tick population. Taken together, these results illustrate the role of ticks as important virus reservoirs, highlighting the need for adequate tick control measures

Clinical relevance of plasma virome dynamics in liver transplant recipients

BACKGROUND: The role of the microbiome in liver transplantation (LT) outcome has received a growing interest in the past decades. In contrast to bacteria, the role of endogenous viral communities, known as the virome, is poorly described. Here, we applied a viral metagenomic approach to study the dynamic evolution of circulating viruses in the plasma of LT recipients and its effect on the clinical course of patients. METHODS: Patients chronically infected with hepatitis B virus (HBV) that received a LT due to endstage liver disease were included in this study. Longitudinal plasma samples were collected pre- and post-LT. Intact viral particles were isolated and sequenced on an Illumina HiSeq 2500 platform. Short read libraries were analysed with an in-house bioinformatics pipeline. Key endpoints were the dynamics of viral families and post-LT complications. FINDINGS: The initiation of immunosuppression induced a bloom of the Anelloviridae that dominated the post-LT plasma virome. A variety of post-LT complication were observed. Nephrotoxicity was reported in 38% of the patients and was associated with a high abundance of anelloviruses. Besides nephrotoxicity, 16 (67%) patients experienced flares of viral or bacterial infections in post-transplant follow-up. These flares were recognized by an increased burden of anelloviruses (p < 0.05). Interestingly, no mortality was observed in patients infected with human pegivirus. INTERPRETATION: These findings suggest a diagnostic potential for the Anelloviridae family in post-LT complications. Furthermore, the impact of human pegivirus infection on post-transplant survival should be further investigated. FUNDING: This trial was supported by Gilead Sciences grant number BE-2017-000133.status: publishe