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1.
Viruses ; 16(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38932117

RESUMO

The alewife (Alosa pseudoharengus) is an anadromous herring that inhabits waters of northeastern North America. This prey species is a critical forage for piscivorous birds, mammals, and fishes in estuarine and oceanic ecosystems. During a discovery project tailored to identify potentially emerging pathogens of this species, we obtained the full genome of a novel hepadnavirus (ApHBV) from clinically normal alewives collected from the Maurice River, Great Egg Harbor River, and Delaware River in New Jersey, USA during 2015-2018. This previously undescribed hepadnavirus contained a circular DNA genome of 3146 nucleotides. Phylogenetic analysis of the polymerase protein placed this virus in the clade of metahepadnaviruses (family: Hepadnaviridae; genus: Metahepadnavirus). There was no evidence of pathology in the internal organs of infected fish and virions were not observed in liver tissues by electron microscopy. We developed a Taqman-based quantitative (qPCR) assay and screened 182 individuals collected between 2015 and 2018 and detected additional qPCR positives (n = 6). An additional complete genome was obtained in 2018 and it has 99.4% genome nucleotide identity to the first virus. Single-nucleotide polymorphisms were observed between the two genomes, including 7/9 and 12/8 synonymous vs nonsynonymous mutations across the polymerase and surface proteins, respectively. While there was no evidence that this virus was associated with disease in this species, alewives are migratory interjurisdictional fishes of management concern. Identification of microbial agents using de novo sequencing and other advanced technologies is a critical aspect of understanding disease ecology for informed population management.


Assuntos
Doenças dos Peixes , Peixes , Genoma Viral , Hepadnaviridae , Filogenia , Animais , Doenças dos Peixes/virologia , Hepadnaviridae/genética , Hepadnaviridae/classificação , Hepadnaviridae/isolamento & purificação , Peixes/virologia , Genômica/métodos , Infecções por Hepadnaviridae/veterinária , Infecções por Hepadnaviridae/virologia , New Jersey
2.
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
3.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
J Vet Med Sci ; 85(6): 642-646, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37183016

RESUMO

The novel domestic cat hepadnavirus (DCH), a member of the Hepadnaviridae, was first detected in Australia and has recently been identified in more countries. In this study, we explored the DCH genome using next-generation sequencing of a plasma sample from a cat with a fever of unknown cause. Nucleotide sequence analysis showed the virus to be relatively genetically distant from the first reported DCH in Australia, showing 89% homology. Then we conducted an epidemiological survey by PCR of plasma samples collected from 203 cats that visited a veterinary hospital for diagnosis and treatment. Two of the 203 surveyed cats a were positive for DCH. One of the two positive cases had elevated liver enzymes of unknown etiology, and the other had hepatocellular adenoma. Our study indicated that DCH infection was observed in domestic cats in the Tokyo area of Japan as well as other reported areas in the world. Further investigations are needed to define the clinical importance of DCH.


Assuntos
Doenças do Gato , Hepadnaviridae , Animais , Gatos , Japão/epidemiologia , Hepadnaviridae/genética , Tóquio , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Doenças do Gato/diagnóstico , Doenças do Gato/epidemiologia
12.
Nat Commun ; 14(1): 1574, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949039

RESUMO

The discovery of nackednaviruses provided new insight into the evolutionary history of the hepatitis B virus (HBV): The common ancestor of HBV and nackednaviruses was non-enveloped and while HBV acquired an envelope during evolution, nackednaviruses remained non-enveloped. We report the capsid structure of the African cichlid nackednavirus (ACNDV), determined by cryo-EM at 3.7 Å resolution. This enables direct comparison with the known capsid structures of HBV and duck HBV, prototypic representatives of the mammalian and avian lineages of the enveloped Hepadnaviridae, respectively. The sequence identity with HBV is 24% and both the ACNDV capsid protein fold and the capsid architecture are very similar to those of the Hepadnaviridae and HBV in particular. Acquisition of the hepadnaviral envelope was thus not accompanied by a major change in capsid structure. Dynamic residues at the spike tip are tentatively assigned by solid-state NMR, while the C-terminal domain is invisible due to dynamics. Solid-state NMR characterization of the capsid structure reveals few conformational differences between the quasi-equivalent subunits of the ACNDV capsid and an overall higher capsid structural disorder compared to HBV. Despite these differences, the capsids of ACNDV and HBV are structurally highly similar despite the 400 million years since their separation.


Assuntos
Proteínas do Capsídeo , Hepadnaviridae , Animais , Proteínas do Capsídeo/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Capsídeo/metabolismo , Hepadnaviridae/metabolismo , Mamíferos/metabolismo
13.
J Vet Diagn Invest ; 35(2): 139-144, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36786316

RESUMO

Domestic cat hepadnavirus (DCH) is a novel hepadnavirus, first identified in 2018. DCH is generally detected using conventional PCR assays, which include time-consuming agarose gel electrophoresis. We developed a rapid, sensitive, and specific real-time PCR (rtPCR) assay for the detection of the DCH genome. To streamline the procedure, our rtPCR assay was carried out using blood samples, without DNA extraction. A consensus primers/probe set was designed based on the nucleotide sequences of the surface/polymerase gene of all DCH strains available in GenBank. To exclude the possibility that the PCR reaction was blocked by anticoagulants, we also used a primers/probe set for amplifying the cat beta-actin gene as a reference gene. Our direct duplex rtPCR assay had high sensitivity, with a limit of detection of 10 copies/µL of blood for DCH. Our direct duplex rtPCR assay should be a useful tool for DCH detection and surveillance.


Assuntos
Hepadnaviridae , Gatos , Animais , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Reação em Cadeia da Polimerase em Tempo Real/métodos , Hepadnaviridae/genética , Primers do DNA/genética , Técnicas de Amplificação de Ácido Nucleico/veterinária , Sequência de Bases , Sensibilidade e Especificidade
14.
Viruses ; 15(1)2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36680190

RESUMO

Domestic cat hepadnavirus (DCH) is an emerging virus related to the hepatitis B virus (HBV). The pathogenic potential of DCH in cats remains to be established. The molecular prevalence of DCH varies widely in the regions investigated so far. The aim of this study was to determine the prevalence, load, and risk factors for DCH detection among cats in Hong Kong, and to generate molecular and epidemiological data on the DCH strains circulating in cats in Hong Kong. DCH DNA was detected using DCH-specific qPCR in 57/513 (11.1%) residual diagnostic blood samples from owned cats. The median viral load was 8.85 × 103 copies/mL of whole blood (range for the 5th to the 95th percentile, 3.33 × 103 to 2.2 × 105 copies per mL). Two outliers had higher viral loads of 1.88 × 107 copies/mL and 4.90 × 109 copies/mL. DCH was detected in cats from 3 months to 19 years of age. Sex, age, neuter status, breed, or elevated serum alanine aminotransferase were not statistically associated with DCH DNA detection. On phylogenetic analysis based on 12 complete genome sequences, the Hong Kong DCH viruses clustered in Genotype A with viruses from Australia and Asia (clade A1), distinct from viruses from Europe (clade A2). Sequence analysis found that DCH has similar epsilon and direct repeat regions to human HBV, suggesting a conserved method of replication. Based on our findings, the DCH strains circulating in Hong Kong are a continuum of the Asiatic strains.


Assuntos
Hepadnaviridae , Gatos , Animais , Humanos , Hong Kong/epidemiologia , Filogenia , Hepadnaviridae/genética , Epidemiologia Molecular , Fatores de Risco
15.
Viruses ; 16(1)2023 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-38257747

RESUMO

Cat ownership is common in Chile, but data on the regional prevalence of infectious agents are limited. A sero-molecular survey of 120 client- or shelter-owned domestic cats in greater Santiago was performed. Whole blood DNA was tested for the novel hepatitis-B-like virus, domestic cat hepadnavirus (DCH) by conventional PCR (cPCR) and quantitative PCR (qPCR), and for feline leukaemia virus (FeLV) by qPCR. Point-of-care serology for FeLV p27 antigen and antibodies recognising feline immunodeficiency virus (FIV) p15 and p24 was performed. DCH DNA was detected in the serum of 2/120 cats (1.67%). Sequencing and phylogenetic analysis showed that the DCH detected in Chile occupies a position outside the main clustering of DCH in the near-complete genome tree. Progressive (antigen-positive, provirus-positive) and regressive (antigen-negative, provirus-positive) FeLV infections were identified in 6/120 (5%) and 9/120 (7.5%) of cats. A total of 2/120 (1.7%) cats had dual FeLV/FIV infection, and another 2 cats had FIV infection alone. This study shows that the global footprint of DCH includes South America with a low molecular frequency in Chile, similar to that reported in the USA. Progressive FeLV infection is relatively common in urban Chile, and male cats are at greater risk than females. Testing and control measures for pathogenic retroviruses are indicated. The potential impact of FeLV, FIV and DCH on Chile's wildcat species is worthy of further investigation.


Assuntos
Hepadnaviridae , Vírus da Imunodeficiência Felina , Leucemia Felina , Humanos , Feminino , Gatos , Animais , Retroviridae , Chile/epidemiologia , Filogenia , Vírus da Leucemia Felina/genética , Vírus da Imunodeficiência Felina/genética , DNA
16.
Viruses ; 14(10)2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298647

RESUMO

Hepadnaviruses are partially double-stranded DNA viruses that infect a variety of species. The prototypical virus in this family is the human hepatitis B virus, which chronically infects approximately 400 million people worldwide and is a risk factor for progressive liver disease and liver cancer. The first hepadnavirus isolated from carnivores was a domestic cat hepadnavirus (DCH), initially identified in Australia and subsequently detected in cats in Europe and Asia. As with all characterized hepadnaviruses so far, DCH infection has been associated with hepatic disease in its host. Prevalence of this infection in the United States has not been explored broadly. Thus, we utilized conventional and quantitative PCR to screen several populations of domestic cats to estimate DCH prevalence in the United States. We detected DCH DNA in 1 out of 496 animals (0.2%) in the U.S. cohort. In contrast, we detected circulating DCH DNA in 7 positive animals from a cohort of 67 domestic cats from Australia (10.4%), consistent with previous studies. The complete consensus genome of the U.S. DCH isolate was sequenced by Sanger sequencing with overlapping PCR products. An in-frame deletion of 157 bp was identified in the N-terminus of the core open reading frame. The deletion begins at the direct repeat 1 sequence (i.e., the 5' end of the expected double-stranded linear DNA form), consistent with covalently closed circular DNA resultant from illegitimate recombination described in other hepadnaviruses. Comparative genome sequence analysis indicated that the closest described relatives of the U.S. DCH isolate are those previously isolated in Italy. Motif analysis supports DCH using NTCP as an entry receptor, similar to human HBV. Our work indicates that chronic DCH prevalence in the U.S. is likely low compared to other countries.


Assuntos
Hepadnaviridae , Gatos , Humanos , Estados Unidos/epidemiologia , Animais , Hepadnaviridae/genética , Prevalência , Vírus da Hepatite B/genética , Análise de Sequência de DNA/veterinária , DNA Circular , Genômica , DNA Viral/genética
17.
J Vet Intern Med ; 36(5): 1648-1659, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36054642

RESUMO

BACKGROUND: Whether domestic cat hepadnavirus (DCH) infection is associated with clinical disease remains to be determined. OBJECTIVES: To determine the relationship between DCH detection, hematology, serum bichemistry and liver histology in DCH-positive cats. ANIMALS: One thousand twenty-two cats in Thailand without concurrent diseases and not undergoing treatments adversely affecting the liver. METHODS: Retrospective cross-sectional study. Samples derived from cats with concurrent virus detection were excluded. DCH detection was determined in blood and fresh-frozen liver by quantitative polymerase chain reaction (qPCR) and further investigated in liver sections showing histological parenchymal disorders (HPD) and normal liver (HNL) using in situ hybridization (ISH). Proliferative/apoptotic activities were determined using immunohistochemistry and ISH panels. Biochemical variables and risk factors for DCH infection were investigated. RESULTS: Six hundred sixty-one (557 blood and 119 liver samples) cats were included. DCH was detected in 18.50% (103/557), 13.85% (9/65), and 3.70% (2/54) of the blood, HPD, and HNL groups, respectively. Cats with DCH revealed abnormally high activity of aspartate aminotransferase (AST) (P = .001) and alanine aminotransferase (ALT) (P < .001). Among DCH-positive HPD case 2/9 an 7/9 were acute and chronic hepatitis, of which 4/7 had hepatitis. Log viral copy number (LVCN) was positively correlated with ALT (P < .001), triglyceride (P < .001), and gamma-glutamyl transpeptidase (GGT) (P = .022). The LVCN also had a positive association with degree of hepatitis (P < .05). There was hepatocyte proliferation activity in DHC positive cats. CONCLUSION AND CLINICAL IMPORTANCE: Domestic cat hepadnavirus infection was associated with high serum activity of liver enzymes and chronic lymphoplasmacytic hepatitis (LPH).


Assuntos
Doenças do Gato , Hepadnaviridae , Hepatopatias , Alanina Transaminase , Animais , Aspartato Aminotransferases , Gatos , Estudos Transversais , Hepatite Crônica/veterinária , Hepatopatias/veterinária , Estudos Retrospectivos , Triglicerídeos , gama-Glutamiltransferase
18.
PLoS Pathog ; 18(7): e1010739, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35901192

RESUMO

Hepadnaviruses use extensively overlapping genes to expand their coding capacity, especially the precore/core genes encode the precore and core proteins with mostly identical sequences but distinct functions. The precore protein of the woodchuck hepatitis virus (WHV) is N-glycosylated, in contrast to the precore of the human hepatitis B virus (HBV) that lacks N-glycosylation. To explore the roles of the N-linked glycosylation sites in precore and core functions, we substituted T77 and T92 in the WHV precore/core N-glycosylation motifs (75NIT77 and 90NDT92) with the corresponding HBV residues (E77 and N92) to eliminate the sequons. Conversely, these N-glycosylation sequons were introduced into the HBV precore/core gene by E77T and N92T substitutions. We found that N-glycosylation increased the levels of secreted precore gene products from both HBV and WHV. However, the HBV core (HBc) protein carrying the E77T substitution was defective in supporting virion secretion, and during infection, the HBc E77T and N92T substitutions impaired the formation of the covalently closed circular DNA (cccDNA), the critical viral DNA molecule responsible for establishing and maintaining infection. In cross-species complementation assays, both HBc and WHV core (WHc) proteins supported all steps of intracellular replication of the heterologous virus while WHc, with or without the N-glycosylation sequons, failed to interact with HBV envelope proteins for virion secretion. Interestingly, WHc supported more efficiently intracellular cccDNA amplification than HBc in the context of either HBV or WHV. These findings reveal novel determinants of precore secretion and core functions and illustrate strong constraints during viral host adaptation resulting from their compact genome and extensive use of overlapping genes.


Assuntos
Hepadnaviridae , Vírus da Hepatite B da Marmota , Hepatite B , DNA Circular , DNA Viral , Homologia de Genes , Glicosilação , Hepadnaviridae/genética , Hepatite B/genética , Vírus da Hepatite B/genética , Adaptação ao Hospedeiro , Humanos , Replicação Viral/genética
19.
Viruses ; 14(7)2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35891523

RESUMO

Chronic hepatitis and hepatocellular carcinoma (HCC) caused by the hepadnavirus hepatitis B virus (HBV) are significant causes of human mortality. A hepatitis-B-like virus infecting cats, domestic cat hepadnavirus (DCH), was reported in 2018. DCH DNA is hepatotropic and detectable in feline blood or serum (3.2 to 12.3%). Detection of HBV DNA has been reported in sera from 10% of free-roaming dogs in Brazil, whereas 6.3% of sera from dogs in Italy tested positive for DCH DNA by real-time quantitative PCR (qPCR). If DCH, HBV, or another hepadnavirus is hepatotropic in dogs, a role for such a virus in the etiology of canine idiopathic chronic hepatitis (CH) or HCC warrants investigation. This study investigated whether DCH DNA could be detected via qPCR in blood from dogs in Hong Kong and also whether liver biopsies from dogs with confirmed idiopathic CH or HCC contained hepadnaviral DNA using two panhepadnavirus conventional PCRs (cPCR) and a DCH-specific cPCR. DCH DNA was amplified from 2 of 501 (0.4%) canine whole-blood DNA samples. A second sample taken 6 or 7 months later from each dog tested negative in DCH qPCR. DNA extracted from 101 liver biopsies from dogs in Hong Kong or the USA, diagnosed by board-certified pathologists as idiopathic CH (n = 47) or HCC (n = 54), tested negative for DCH DNA and also tested negative using panhepadnavirus cPCRs. This study confirms that DCH DNA can be detected in canine blood by qPCR, although at a much lower prevalence than that reported previously. We identified no evidence to support a pathogenic role for a hepadnavirus in canine idiopathic CH or HCC.


Assuntos
Carcinoma Hepatocelular , Hepadnaviridae , Neoplasias Hepáticas , Animais , Biópsia , Carcinoma Hepatocelular/veterinária , Gatos , DNA Viral/genética , Cães , Hepadnaviridae/genética , Vírus da Hepatite B/genética , Hepatite Crônica , Hong Kong , Humanos
20.
Vet Rec ; 191(4): e1626, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35393638

RESUMO

BACKGROUND: The association between domestic cat hepadnavirus (DCH) infection and feline chronic hepatitis and hepatocellular carcinoma has been suggested. However, studies focused on the association between DCH infection and clinicopathological changes consistent with liver disease in cats are not available. METHODS: This retrospective investigation included sera obtained from 96 cats that had the serum activity of at least alanine aminotransferase or alkaline phosphatase measured during initial diagnostic work-up. Based on these haematobiochemical results, cats were categorised according to their likelihood of having liver disease (absent, low, intermediate or high). DCH DNA was detected using real-time PCR, nested PCR and sequencing. RESULTS: Overall, potential liver damage was observed in 44 cats, including cats with low (n = 14), intermediate (n = 10) and high (n = 20) likelihood of liver disease. Four cats (4.2%) were DCH-positive, with three positive cats belonging to the liver disease group (two with low and one with intermediate likelihood of liver disease). CONCLUSIONS: Although the pathogenic potential of DCH in cats still has to be clarified, these results suggest that DCH testing should not be based only on the presence of biochemical changes potentially consistent with liver disease.


Assuntos
Carcinoma Hepatocelular , Doenças do Gato , Hepadnaviridae , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/veterinária , Doenças do Gato/diagnóstico , Gatos , Hepadnaviridae/genética , Neoplasias Hepáticas/veterinária , Estudos Retrospectivos , Viremia/veterinária
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