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1.
Infect Genet Evol ; 122: 105618, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38857639

RESUMO

Hepatitis B virus (HBV) belongs to the family Hepadnaviridae and is the smallest human DNA virus, with a genome that is only 3200 nucleotides long. The absence of proofreading function in HBV reverse transcriptase provides a wide range of genetic variants for targeted outgrowth at different stages of infection. A number of sub genotypes and ten HBV genotypes (A through J) have been identified through analyses of the divergence of HBV genomic sequences. Numerous clinical outcomes, including the emergence of chronicity, the course of the disease, the effectiveness of treatment, and the response to vaccination, have been related to differences in genotype between HBV isolates. There are just seven studies that have been done in Ethiopia that examine the molecular epidemiology of HBV. Moreover, these studies haven't been compiled and reviewed yet. In this review, we looked at the genetic diversity and molecular epidemiology of HBV, the relationship between HBV genotypes and clinical outcomes, the immunopathogenesis of HBV, and finally the molecular epidemiology of HBV in Ethiopia. PubMed, Embase, and Google Scholar search engines were used to find relevant articles for the review. By using HBV genotyping, clinicians can better tailor vaccination decisions and antiviral therapy for patients with chronic hepatitis B who are more likely to experience the disease's progression.


Assuntos
Vírus da Hepatite B , Epidemiologia Molecular , Vírus da Hepatite B/genética , Humanos , Etiópia/epidemiologia , Genótipo , Hepatite B/epidemiologia , Hepatite B/virologia , Variação Genética , Filogenia
2.
Front Vet Sci ; 11: 1385033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756526

RESUMO

Avihepadnavirus is a genus of the Hepadnaviridae family. It primarily infects birds, including species of duck, geese, cranes, storks, and herons etc. To understand the genetic relatedness and evolutionary diversity among avihepadnavirus strains, a comprehensive analysis of the available 136 full-length viral genomes (n = 136) was conducted. The genomes were classified into two major genotypes, i.e., GI and GII. GI viruses were further classified into 8 sub-genotypes including DHBV-I (duck hepatitis B virus-I), DHBV-II (Snow goose Hepatitis B, SGHBV), DHBV-III, RGHBV (rossgoose hepatitis B virus), CHBV (crane hepatitis B virus), THBV (Tinamou hepatitis B virus), STHBV (stork hepatitis B virus), and HHBV (Heron hepatitis B virus). DHBV-I contains two sub-clades DHBV-Ia and DHBV-Ib. Parrot hepatitis B virus (PHBV) stains fall into GII which appeared as a separate phylogenetic branch/clade. All the subtypes of viruses in GI and GII seem to be genetically connected with viruses of DHBV-I by multiple mutational steps in phylogeographic analysis. Furthermore, 16 potential recombination events among different sub-genotypes in GI and one in GII were identified, but none of which is inter-genotypic between GI and GII. Overall, the results provide a whole picture of the genetic relatedness of avihepadnavirus strains, which may assist in the surveillance of virus spreading.

3.
Viruses ; 16(4)2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38675950

RESUMO

Hepatitis B virus (HBV) is the etiologic agent of chronic hepatitis B, which puts at least 300 million patients at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. HBV is a partially double-stranded DNA virus of the Hepadnaviridae family. While HBV was discovered more than 50 years ago, many aspects of its replicative cycle remain incompletely understood. Central to HBV persistence is the formation of covalently closed circular DNA (cccDNA) from the incoming relaxed circular DNA (rcDNA) genome. cccDNA persists as a chromatinized minichromosome and is the major template for HBV gene transcription. Here, we review how cccDNA and the viral minichromosome are formed and how viral gene transcription is regulated and highlight open questions in this area of research.


Assuntos
DNA Circular , DNA Viral , Vírus da Hepatite B , Replicação Viral , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , DNA Circular/genética , Humanos , DNA Viral/genética , Transcrição Viral/genética , Regulação Viral da Expressão Gênica , Transcrição Gênica , Genoma Viral , Hepatite B Crônica/virologia , Hepatite B/virologia , Replicação do DNA
4.
Pathogens ; 13(2)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38392888

RESUMO

Studies of marine fish have revealed distant relatives of viruses important to global fish and animal health, but few such studies exist for freshwater fish. To investigate whether freshwater fish also host such viruses, we characterized the viromes of five wild species of freshwater fish in Wisconsin, USA: bluegill (Lepomis macrochirus), brown trout (Salmo trutta), lake sturgeon (Acipenser fulvescens), northern pike (Esox lucius), and walleye (Sander vitreus). We analyzed 103 blood serum samples collected during a state-wide survey from 2016 to 2020 and used a metagenomic approach for virus detection to identify known and previously uncharacterized virus sequences. We then characterized viruses phylogenetically and quantified prevalence, richness, and relative abundance for each virus. Within these viromes, we identified 19 viruses from 11 viral families: Amnoonviridae, Circoviridae, Coronaviridae, Hepadnaviridae, Peribunyaviridae, Picobirnaviridae, Picornaviridae, Matonaviridae, Narnaviridae, Nudnaviridae, and Spinareoviridae, 17 of which were previously undescribed. Among these viruses was the first fish-associated coronavirus from the Gammacoronavirus genus, which was present in 11/15 (73%) of S. vitreus. These results demonstrate that, similar to marine fish, freshwater fish also harbor diverse relatives of viruses important to the health of fish and other animals, although it currently remains unknown what effect, if any, the viruses we identified may have on fish health.

5.
Antiviral Res ; 224: 105835, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401714

RESUMO

Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients. A subset of patients achieve functional cure, whereas the others exhibit a moderate response or are non-responders. NAP efficacy has been difficult to recapitulate in animal models, with the duck hepatitis B virus (DHBV) model showing some promise but remaining underexplored for NAP efficacy testing. Here we report on an optimized in vivo DHBV duck model and explore several characteristics of NAP treatment. REP2139 was efficacious in reducing DHBV DNA and DHBsAg levels in approximately half of the treated ducks, whether administered intraperitoneally or subcutaneously. Intrahepatic or serum NAP concentrations did not correlate with efficacy, nor did the appearance of anti-DHBsAg antibodies. Furthermore, NAP efficacy was only observed in experimentally infected ducks, not in endogenously infected ducks (vertical transmission). REP2139 add-on to entecavir treatment induced a deeper and more sustained virological response compared to entecavir monotherapy. Destabilized REP2165 showed a different activity profile with a more homogenous antiviral response followed by a faster rebound. In conclusion, subcutaneous administration of NAPs in the DHBV duck model provides a useful tool for in vivo evaluation of NAPs. It recapitulates many aspects of this class of compound's efficacy in CHB patients, most notably the clear division between responders and non-responders.


Assuntos
Infecções por Hepadnaviridae , Vírus da Hepatite B do Pato , Hepatite B Crônica , Hepatite Viral Animal , Ácidos Nucleicos , Animais , Humanos , Vírus da Hepatite B do Pato/genética , Hepatite B Crônica/tratamento farmacológico , Antivirais/farmacologia , Ácidos Nucleicos/uso terapêutico , Polímeros/uso terapêutico , Resultado do Tratamento , Patos/genética , DNA Viral , Hepatite Viral Animal/tratamento farmacológico , Vírus da Hepatite B , Infecções por Hepadnaviridae/tratamento farmacológico , Infecções por Hepadnaviridae/veterinária , Fígado
6.
Viruses ; 16(2)2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38399943

RESUMO

Understanding the local epidemiology of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in Hong Kong will inform retrovirus prevention strategies. Domestic cat hepadnavirus (DCH), a novel hepatitis-B-like virus, is commonly detected among client-owned cats in Hong Kong, but community cats have not been studied. The aims of this study were to investigate the frequency and potential risk factors for (i) FeLV and FIV among community and client-owned cats and (ii) perform molecular detection of DCH among community cats in Hong Kong. Blood samples from 713 cats were obtained from client-owned (n = 415, residual diagnostic) and community cats (n = 298, at trap-neuter-return). Point-of-care (POC) testing for FeLV antigen and feline immunodeficiency virus (FIV) anti-p15 and p24 antibodies was performed. FeLV-positive samples were progressed to p27 sandwich enzyme-linked immunosorbent assay. Whole blood DNA was tested with qPCRs for FeLV U3 and gag, and nested PCRs where additional information was required. DCH qPCR was performed on a subset of community cats (n = 193). A single, regressive, FeLV infection was detected in a client-owned cat (1/415 FeLV U3 qPCR positive, 0.2%, 95% CI 0.0-1.3%). Five/415 client-owned cats tested presumably false FeLV-antigen positive (qPCR negative). No markers of FeLV infection were detected in community cats (0/298; 0%). FIV seroprevalence was much higher in community cats (46/298, 15.4%) than in client-owned cats (13/415, 3.1%) (p < 0.001). Mixed breed was a risk factor for FIV infection in client-owned cats. Neither sex nor age were associated with FIV infection. DCH DNA was detected in 34/193 (17.6%) community cats (median viral load 6.32 × 103 copies/reaction). FeLV infection is rare in Hong Kong, negatively impacting the positive predictive value of diagnostic tests. FeLV-antigen testing remains the screening test of choice, but confirmation of a positive result using FeLV qPCR is essential. FIV infection is common in community cats and the absence of a sex predisposition, seen previously in cats managed similarly, raises questions about virus-transmission dynamics in these groups. DCH infection is very common in Hong Kong, both in client-owned and community cats, highlighting the importance of understanding the pathogenic potential of this virus for cats.


Assuntos
Doenças do Gato , Síndrome de Imunodeficiência Adquirida Felina , Hepadnaviridae , Vírus da Imunodeficiência Felina , Leucemia Felina , Humanos , Animais , Gatos , Retroviridae/genética , Hepadnaviridae/genética , Estudos Soroepidemiológicos , Hong Kong/epidemiologia , Vírus da Imunodeficiência Felina/genética , Vírus da Leucemia Felina/genética , Anticorpos Antivirais , DNA , Doenças do Gato/diagnóstico , Doenças do Gato/epidemiologia
7.
Viruses ; 16(1)2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38275959

RESUMO

We are grateful to the authors for providing additional data to demonstrate the presence of domestic cat hepadnavirus in lymphoma tissues [...].


Assuntos
Hepadnaviridae , Linfoma , Gatos , Animais , Linfoma/veterinária
9.
Rev. epidemiol. controle infecç ; 13(4): 223-231, out.-dez. 2023. ilus
Artigo em Inglês, Português | LILACS | ID: biblio-1532326

RESUMO

Background and Objective: Hepatitis B is an infectious disease caused by a virus from the hepadnaviridae family, with worldwide distribution, and represents a serious global health problem. The pathology may have been affected by the COVID-19 pandemic, caused by the SARS-CoV-2 virus, making it possible for serious outcomes to occur when overlapping viral types. This study sought to describe the levels of scientific evidence of research carried out on the topic, establishing a relationship between hepatitis B virus infection and SARS-CoV-2 infection. Content: integrative literature review, with searches performed in the databases of the Medical Literature Analysis and Retrieval System Online, and Scientific Electronic Library Online, with analysis centered on the description of the methodological design, and on the classification of the level of evidence. Conclusion: the scientific production on hepatitis B associated with SARS-CoV-2 infection corresponds mostly to studies with a low level of evidence. The selected publications presented limitations such as the occurrence of studies with a small number of samples, lack of subsidiary data of patients in treatment, and occurrence of non-randomized selection. The results suggest the need for further investigations for the purpose of technological improvement, identification of risk factors, therapeutic intervention, and advanced clinical investigation, in order to encourage evidence-based healthcare practices.(AU)


Justificativa e Objetivos: a hepatite B é uma doença infectocontagiosa provocada por um vírus da família hepadnaviridae, com distribuição mundial, e representa um grave problema de saúde global. A patologia pode ter sido afetada pela pandemia de COVID-19, provocada pelo vírus SARS-CoV-2, sendo possível a ocorrência de desfechos graves na sobreposição entre os dos tipos virais. Este estudo buscou descrever os níveis de evidências científicas de pesquisas realizadas sobre o tema, estabelecendo relação entre a infecção por vírus da hepatite B e a infecção por SARS-CoV-2. Conteúdo: revisão integrativa da literatura, com buscas realizadas nas bases de dados do Medical Literature Analysis and Retrieval System Online e Scientific Electronic Library Online, com análise centrada na descrição do delineamento metodológico e na classificação do nível de evidência. Conclusão: a produção científica sobre hepatite B associada a infecção por SARS-CoV-2 corresponde majoritariamente a pesquisas com baixo nível de evidência. As publicações selecionadas apresentaram limitações, como a ocorrência de estudos com número reduzido de amostras, falta de dados subsidiários de pacientes em tratamento e ocorrência de seleção não randomizada. Os resultados sugerem a necessidade de novas investigações para fins de incrementos tecnológicos, identificação de fatores de risco, intervenção terapêutica e investigação clínica avançada, de forma a fomentar práticas assistenciais em saúde baseadas em evidências.(AU)


Justificación y Objetivo: la hepatitis B es una enfermedad infecciosa contagiosa causada por un virus de la familia hepadnaviridae, de distribución mundial, y representa un grave problema de salud mundial. Su patología puede haberse visto afectada por la pandemia de COVID-19, provocada por el virus SARS-CoV-2, y son posibles desenlaces graves cuando se superponen tipos virales. Este estudio buscó describir los niveles de evidencia científica de las investigaciones realizadas sobre el tema, estableciendo una relación entre la infección por el virus de la hepatitis B y la infección por el SARS-CoV-2. Contenido: revisión integradora de la literatura, con búsquedas realizadas en las bases de datos Medical Literature Analysis and Retrieval System Online y Scientific Electronic Library Online, con un análisis centrado en la descripción del diseño metodológico y en la clasificación del nivel de evidencia. Conclusión: la producción científica sobre la hepatitis B asociada a la infección por SARS-CoV-2 corresponde, en su mayoría, a investigaciones con bajo nivel de evidencia. Las publicaciones seleccionadas presentaron limitaciones como la ocurrencia de estudios con un número reducido de muestras, la falta de datos subsidiarios de los pacientes en tratamiento y la ocurrencia de selección no aleatoria. Los resultados sugieren la necesidad de seguir investigando para mejorar la tecnología, identificar los factores de riesgo, intervenir terapéuticamente y realizar investigación clínica avanzada, con el fin de promover prácticas sanitarias basadas en la evidencia.(AU)


Assuntos
Humanos , COVID-19 , Hepatite B , Coinfecção
11.
One Health ; 17: 100641, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38024255

RESUMO

Ectoparasites found on bats are known to contain important microbes. However, the viruses hosted by these obligate parasites are understudied. This has led to the near oversight of the potential role of these ectoparasites in virus maintenance and transmission from bats to other interacting species and the environment. Here, we sampled bat ectoparasites parasitizing a diverse selection of bat species in the families Rhinolophidae, Vespertilionidae, Megadermatidae, Hipposideridae and Pteropodidae in Yunnan Province, China. We show that the ectoparasite prevalence was generally higher in male compared to female bats. Most ectoparasites were found to fall within the Nycteribiidae, Spinturnicidae and Streblidae bat ectoparasite families. We subsequently applied a non-biased sequencing of libraries prepared from the pooled ectoparasites, followed by an in-silico virus-centric analysis of the resultant reads. We show that ectoparasites hosted by the sampled families of bats are found to carry, in addition to a diverse set of phages, vertebrate and insect viruses in the families Aliusviridae, Ascoviridae, Chuviridae, Circoviridae, Flaviviridae, Hepadnaviridae, Hepeviridae, Herpesviridae, Iridoviridae, Marseilleviridae, Nairoviridae, Orthomyxoviridae, Parvoviridae, Poxviridae, Reoviridae, Retroviridae, and Rhabdoviridae. We further report a partial Parvovirus VP1/VP2 gene and partial Poxvirus ubiquitin-like gene predicted by two independent next generation sequencing data analysis pipelines. This study describes the natural virome of bat ectoparasites, providing a platform for understanding the role these ectoparasites play in the maintenance and spread of viruses to other animals.

12.
Viruses ; 15(10)2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37896905

RESUMO

Domestic cat hepadnavirus (DCH) is an infectious disease associated with chronic hepatitis in cats, which suggests a similarity with hepatitis B virus infections in humans. Since its first identification in Australia in 2018, DCH has been reported in several countries with varying prevalence rates, but its presence in Taiwan has yet to be investigated. In this study, we aimed to identify the presence and genetic diversity of DCH infections in Taiwan. Among the 71 samples tested, eight (11.27%) were positive for DCH. Of these positive cases, three cats had elevated levels of alanine transaminase (ALT) and aspartate transaminase (AST), suggesting an association between DCH infection and chronic hepatitis. Four DCH-positive samples were also tested for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) coinfection. One sample (25%) was positive for FIV, whereas there was no positive sample for FeLV (0%). In addition, we performed whole genome sequencing on six samples to determine the viral genome sequences. Phylogenetic analyses identified a distinct lineage compared with previously reported sequences. This study highlights the importance of continuous surveillance of DCH and further research to elucidate the pathophysiology and transmission route of DCH.


Assuntos
Doenças do Gato , Hepadnaviridae , Vírus da Imunodeficiência Felina , Humanos , Animais , Gatos , Hepadnaviridae/genética , Filogenia , Taiwan/epidemiologia , Vírus da Imunodeficiência Felina/genética , Vírus da Leucemia Felina , Hepatite Crônica , Variação Genética , Doenças do Gato/epidemiologia
13.
Glob Health Med ; 5(4): 199-207, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37655181

RESUMO

Hepatitis B virus (HBV) is a hepadnavirus, a small DNA virus that infects liver tissue, with some unusual replication steps that share similarities to retroviruses. HBV infection can lead to chronic hepatitis B (CHB), a life-long infection associated with significant risks of liver disease, especially if untreated. HBV is a significant global health problem, with hundreds of millions currently living with CHB. Currently approved strategies to prevent or inhibit HBV are highly effective, however, a cure for CHB has remained elusive. To achieve a cure, elimination of the functionally integrated HBV covalently closed chromosomal DNA (cccDNA) genome is required. The capsid core is an essential component of HBV replication, serving roles when establishing infection and in creating new virions. Over the last two and a half decades, significant efforts have been made to find and characterize antivirals that target the capsid, specifically the HBV core protein (Cp). The antivirals that interfere with the kinetics and morphology of the capsid, termed capsid assembly modulators (CAMs), are extremely potent, and clinical investigations indicate they are well tolerated and highly effective. Several CAMs offer the potential to cure CHB by decreasing the cccDNA pools. Here, we review the biology of the HBV capsid, focused on Cp, and the development of inhibitors that target it.

14.
Front Vet Sci ; 10: 1248445, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37732146

RESUMO

Domestic cat hepadnavirus (DCH) belongs to the Hepadnaviridae family together with human hepatitis B virus (HBV) that remains to be a major health problem worldwide. The transmission of HBV infectious virion has been one of the essential factors that contribute to high number of HBV infection in humans. It has been long known that various body fluid specimens of human with chronic HBV infection contain HBV DNA and demonstrated to be infectious. In contrast to this knowledge, the detection of DCH in various body fluid specimens of cats, has not been reported. This study explored the detection of DCH DNA in various body fluid specimens of cats by quantitative polymerase chain reaction (qPCR) and investigated whether the detection of DCH DNA from broader routes was correlated with any genomic diversity by phylogenetic analysis. A total of 1,209 body fluid specimens were included, and DCH DNA was detected not only in 4.70% (25/532) of blood samples; but also in 12.5% (1/8), 1.14% (1/88), 2.54% (10/394), and 1.65% (3/182) of auricular swab (AS), nasal swab (NS), oral swab (OS), and rectal swab (RS) specimens, respectively. Furthermore, the level of DCH DNA detected in the blood was significantly correlated with DCH DNA detection in OS (P = 0.02) and RS (P = 0.04) specimens. Genomic analysis revealed that there was no notable genomic diversity within the complete genome sequences obtained in this study. In conclusion, this study highlighted the presence of DCH DNA in various body fluid specimens of cats, and the potential role of these specimens in DCH horizontal transmission within the cat population warrants further studies.

15.
Microorganisms ; 11(9)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37764048

RESUMO

Genotype I, the penultimate HBV genotype to date, was granted the status of a bona fide genotype only in the XXIst century after some hesitations. The reason for these hesitations was that genotype I is a complex recombinant virus formed with segments from three original genotypes, A, C, and G. It was estimated that genotype I is responsible for only an infinitesimal fraction (<1.0%) of the chronic HBV infection burden worldwide. Furthermore, most probably due to its recent discovery and rarity, the natural history of infection with genotype I is poorly known in comparison with those of genotypes B or C that predominate in their area of circulation. Overall, genotype I is a minor genotype infecting ethnic minorities. It is endemic to the Southeast Asian Massif or Eastern Zomia, a vast mountainous or hilly region of 2.5 million km2 spreading from Eastern India to China, inhabited by a little more than 100 million persons belonging primarily to ethnic minorities speaking various types of languages (Tibeto-Burman, Austroasiatic, and Tai-Kadai) who managed to escape the authority of central states during historical times. Genotype I consists of two subtypes: I1, present in China, Laos, Thailand, and Vietnam; and I2, encountered in India, Laos, and Vietnam.

16.
Vet Q ; 43(1): 1-10, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37768269

RESUMO

Domestic cat hepadnavirus (DCH), a relative hepatitis B virus (HBV) in human, has been recently identified in cats; however, association of DCH infection with lymphoma in cats is not investigated. To determine the association between DCH infection and feline lymphoma, seven hundred and seventeen cats included 131 cats with lymphoma (68 blood and 63 tumor samples) and 586 (526 blood and 60 lymph node samples) cats without lymphoma. DCH DNA was investigated in blood and formalin-fixed paraffin-embedded (FFPE) tissues by quantitative polymerase chain reaction (qPCR). The FFPE lymphoma tissues were immunohistochemically subtyped, and the localization of DCH in lymphoma sections was investigated using in situ hybridization (ISH). Feline retroviral infection was investigated in the DCH-positive cases. DCH DNA was detected in 16.18% (11/68) (p = 0.002; odds ratio [OR], 5.15; 95% confidence interval [CI], 2.33-11.36) of blood and 9.52% (6/63) (p = 0.028; OR, 13.68; 95% CI, 0.75-248.36) of neoplastic samples obtained from lymphoma cats, whereas only 3.61% (19/526) of blood obtained from non-lymphoma cats was positive for DCH detection. Within the DCH-positive lymphoma, in 3/6 cats, feline leukemia virus was co-detected, and in 6/6 were B-cell lymphoma (p > 0.9; OR, 1.93; 95% CI, 0.09-37.89) and were multicentric form (p = 0.008; OR, 1.327; 95% CI, 0.06-31.18). DCH was found in the CD79-positive pleomorphic cells. Cats with lymphoma were more likely to be positive for DCH than cats without lymphoma, and infection associated with lymphoma development needs further investigations.


Assuntos
Doenças do Gato , Hepadnaviridae , Linfoma , Humanos , Gatos , Animais , Hepadnaviridae/genética , Linfoma/veterinária , Vírus da Leucemia Felina/genética , DNA
17.
Antiviral Res ; 217: 105695, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536428

RESUMO

The Orthohepadnavirus genus includes hepatitis B virus (HBV) that can cause chronic hepatitis and hepatocarcinoma in humans. Recently, a novel hepadnavirus in cats, domestic cat hepadnavirus (DCH), was identified that is genetically close to HBV. DCH infection is associated with chronic hepatitis in cats, suggesting a similarity with HBV pathogenesis and the potential to use DCH as a novel animal model for HBV research. HBV is shown to use the sodium/bile acid cotransporter (NTCP) as a major cell entry receptor, but the equivalent receptor for DCH remains unknown. Here we sought to identify the entry receptor for DCH. HBV- and DCH-derived preS1 peptides efficiently bound to both human and cat NTCPs, and residue 158 of NTCP proteins determined the species-specific binding of the DCH preS1 peptide. Myrcludex B, an HBV entry inhibitor, blocked the binding of the DCH preS1 peptide. Thus, DCH and HBV may share cell entry molecules, suggesting a possibility of inter-species transmission. Furthermore, our study suggests that DCH can be useful as a novel model for HBV research.


Assuntos
Hepadnaviridae , Hepatite B , Neoplasias Hepáticas , Simportadores , Animais , Gatos , Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/metabolismo , Hepadnaviridae/metabolismo , Vírus da Hepatite B/metabolismo , Hepatite Crônica/metabolismo , Hepatócitos , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Sódio/metabolismo , Simportadores/metabolismo , Internalização do Vírus
18.
Vet Med Sci ; 9(5): 1965-1972, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37471581

RESUMO

BACKGROUND: Domestic cat hepadnaviruses (DCHs) have been described as a novel virus that can infect cats. OBJECTIVE: The aim of our study is the first identification and molecular characterizations of DCH infection in Turkish domestic cats. METHODS: The blood, organ and ascites fluid samples from 550 cats were randomly sampled. The presence of DCH nucleic acid was investigated by using both in the literature and newly designed primers. RESULTS: It was found that the hepadnavirus positivity rate is 4% (22/550) in Türkiye. The full genomic characterization was performed on 13 of 22 samples, and others were characterized as nearly full genome. In this study, we highlight that whole blood samples should be also screened for DCH, not only serum samples as has frequently been done in other studies. DCH-infected cats were also found positive (54.54%, 12/22) for Feline leukaemia virus infection. BLAST results revealed that Turkish DCHs have 86.32%-99.08% homology with strains in the GenBank database, enabling us to construct phylogenetic trees. CONCLUSIONS: According to this study's results, it is suggested that this infection should be added to veterinary diagnostic panels worldwide. Additionally, we suggest that our new synthesized primers for the amplification of X gene can also be used for diagnosis.


Assuntos
Hepadnaviridae , Orthohepadnavirus , Animais , Gatos , Orthohepadnavirus/genética , Filogenia , Hepadnaviridae/genética , Genoma Viral , Genômica
19.
Vet Microbiol ; 284: 109828, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37406408

RESUMO

After the identification of the novel domestic cat hepadnavirus (DCH) in 2018, its potential pathogenetic role in feline hepatic diseases has been suggested. Following the detection of DCH in a cat's serum and peritoneal effusion, the aim of this study was to retrospectively investigate the presence of DCH in cats with and without cavitary effusions along with DCH presence in effusions. Stored serum and effusion samples from cats with and without effusions admitted to the Veterinary Teaching Hospital of Lodi (Italy) in 2020-2022 were included based on results of hematobiochemical parameters. Effusions were classified based on cytological and physicochemical findings. The likelihood of liver damage was estimated based on clinical and laboratory findings. Samples were tested for DCH presence by quantitative PCR (qPCR). Positive samples were subjected to whole genome sequencing and phylogenetic analysis. DCH was detected in both serum and peritoneal effusion samples of 2/72 (2.8%) enrolled cats, included in the group with effusions (2/33; 6.1%), with one cat showing inflammatory and the other non-inflammatory effusion. Both DCH-positive cats belonged to the group with a likelihood of liver damage (2/22, 9.1%). Phylogeny showed that the DCH sequences from this study clustered with the prototypic Australian strain but were not included in the clade with other Italian DCH sequences. Results suggest the circulation of different DCH variants in Italy and show the presence of DCH in effusion samples from DCH-positive cats, mirroring the presence of HBV in body fluids from HBV-infected humans. Further studies are still recommended to define the pathogenic role of DCH in cats.


Assuntos
Doenças do Gato , Hepadnaviridae , Humanos , Gatos , Animais , Estudos Retrospectivos , Hepadnaviridae/genética , Filogenia , Hospitais Veterinários , Austrália , Hospitais de Ensino , Proteínas
20.
Biomedicines ; 11(6)2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37371770

RESUMO

Hepatitis B virus (HBV) is an enveloped DNA human virus belonging to the Hepadnaviridae family. Perhaps its main distinguishable characteristic is the replication of its genome through a reverse transcription process. The HBV circular genome encodes only four overlapping reading frames, encoding for the main canonical proteins named core, P, surface, and X (or HBx protein). However, pre- and post-transcriptional gene regulation diversifies the full HBV proteome into diverse isoform proteins. In line with this, hepatitis B virus X protein (HBx) is a viral multifunctional and regulatory protein of 16.5 kDa, whose canonical reading frame presents two phylogenetically conserved internal in-frame translational initiation codons, and which results as well in the expression of two divergent N-terminal smaller isoforms of 8.6 and 5.8 kDa, during translation. The canonical HBx, as well as the smaller isoform proteins, displays different roles during viral replication and subcellular localizations. In this article, we reviewed the different mechanisms of pre- and post-transcriptional regulation of protein expression that take place during viral replication. We also investigated all the past and recent evidence about HBV HBx gene regulation and its divergent N-terminal isoform proteins. Evidence has been collected for over 30 years. The accumulated evidence simply strengthens the concept of a new paradigm of the canonical HBx, and its smaller divergent N-terminal isoform proteins, not only during viral replication, but also throughout cell pathogenesis.

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