RESUMO
The human hepatitis B virus (HBV) and the duck hepatitis B virus (DHBV) share several fundamental features. Both viruses have a partially double-stranded DNA genome that is replicated via a RNA intermediate and the coding open reading frames (ORFs) overlap extensively. In addition, the genomic and structural organization, as well as replication and biological characteristics, are very similar in both viruses. Most of the key features of hepadnaviral infection were first discovered in the DHBV model system and subsequently confirmed for HBV. There are, however, several differences between human HBV and DHBV. This review will focus on the molecular and cellular biology, evolution, and host adaptation of the avian hepatitis B viruses with particular emphasis on DHBV as a model system.
Assuntos
Avihepadnavirus/genética , Avihepadnavirus/fisiologia , Infecções por Hepadnaviridae/patologia , Sequência de Aminoácidos , Animais , Avihepadnavirus/crescimento & desenvolvimento , Avihepadnavirus/patogenicidade , DNA Viral/genética , Modelos Animais de Doenças , Patos , Infecções por Hepadnaviridae/tratamento farmacológico , Infecções por Hepadnaviridae/fisiopatologia , Vírus da Hepatite B do Pato/genética , Vírus da Hepatite B do Pato/crescimento & desenvolvimento , Vírus da Hepatite B do Pato/patogenicidade , Vírus da Hepatite B do Pato/fisiologia , Dados de Sequência Molecular , Morfogênese/fisiologia , Tropismo/fisiologia , Proteínas Virais/análise , Proteínas Virais/fisiologia , Vacinas Virais/genética , Vacinas Virais/uso terapêutico , Internalização do Vírus , Replicação Viral/fisiologiaRESUMO
Five new hepadnaviruses were cloned from exotic ducks and geese, including the Chiloe wigeon, mandarin duck, puna teal, Orinoco sheldgoose, and ashy-headed sheldgoose. Sequence comparisons revealed that all but the mandarin duck viruses were closely related to existing isolates of duck hepatitis B virus (DHBV), while mandarin duck virus clones were closely related to Ross goose hepatitis B virus. Nonetheless, the S protein, core protein, and functional domains of the Pol protein were highly conserved in all of the new isolates. The Chiloe wigeon and puna teal hepatitis B viruses, the two new isolates most closely related to DHBV, also lacked an AUG start codon at the beginning of their X open reading frame (ORF). But as previously reported for the heron, Ross goose, and stork hepatitis B viruses, an AUG codon was found near the beginning of the X ORF of the mandarin duck, Orinoco, and ashy-headed sheldgoose viruses. In all of the new isolates, the X ORF ended with a stop codon at the same position. All of the cloned viruses replicated when transfected into the LMH line of chicken hepatoma cells. Significant differences between the new isolates and between these and previously reported isolates were detected in the pre-S domain of the viral envelope protein, which is believed to determine viral host range. Despite this, all of the new isolates were infectious for primary cultures of Pekin duck hepatocytes, and infectivity in young Pekin ducks was demonstrated for all but the ashy-headed sheldgoose isolate.
Assuntos
Anseriformes/virologia , Avihepadnavirus/isolamento & purificação , Sequência de Aminoácidos , Animais , Animais Domésticos/virologia , Avihepadnavirus/classificação , Avihepadnavirus/genética , Avihepadnavirus/fisiologia , Sequência de Bases , Linhagem Celular , Galinhas , DNA Viral/genética , Patos/virologia , Feminino , Gansos/virologia , Hibridização In Situ , Masculino , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Proteínas Virais/genética , Virulência , Replicação ViralRESUMO
Hepadnavirus replication occurs in hepatocytes in vivo and in hepatoma cell lines in cell culture. Hepatitis B virus (HBV) replication can occur in nonhepatoma cells when pregenomic RNA synthesis from viral DNA is activated by the expression of the nuclear hormone receptors hepatocyte nuclear factor 4 (HNF4) and the retinoid X receptor alpha (RXR alpha) plus peroxisome proliferator-activated receptor alpha (PPAR alpha) heterodimer. Nuclear hormone receptor-dependent HBV replication is inhibited by hepatocyte nuclear factor 3 (HNF3). In contrast, HNF3 and HNF4 support duck hepatitis B virus (DHBV) replication in nonhepatoma cells, whereas the RXR alpha-PPAR alpha heterodimer inhibits HNF4-dependent DHBV replication. HNF3 and HNF4 synergistically activate DHBV pregenomic RNA synthesis and viral replication. The conditions that support HBV or DHBV replication in nonhepatoma cells are not able to support woodchuck hepatitis virus replication. These observations indicate that avian and mammalian hepadnaviruses have distinct transcription factor requirements for viral replication.
Assuntos
Avihepadnavirus/fisiologia , Proteínas de Ligação a DNA , Regulação Viral da Expressão Gênica , Orthohepadnavirus/fisiologia , Fatores de Transcrição/metabolismo , Replicação Viral , Células 3T3 , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Vírus da Hepatite B do Pato/patogenicidade , Vírus da Hepatite B do Pato/fisiologia , Vírus da Hepatite B/patogenicidade , Vírus da Hepatite B/fisiologia , Fator 4 Nuclear de Hepatócito , Humanos , Fígado/virologia , Camundongos , Fosfoproteínas/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores do Ácido Retinoico/metabolismo , Receptores X de Retinoides , Transcrição Gênica , Células Tumorais CultivadasRESUMO
We have identified and characterized a novel intracellular DNA replicative intermediate that is synthesized by heron hepatitis B virus (HHBV) and not by other avian hepadnaviruses. The new DNA form is synthesized in all host cells tested. The HHBV nucleic acid template, and not HHBV proteins, is responsible for the formation of the new form. The new form is comprised of a full-length minus-strand DNA and an incomplete plus-strand DNA whose 5' ends are mapped to DR2, predominantly. The 3' ends of its plus-strand are located between nucleotides 946 and 1046. Genetic analysis indicates that the sequences responsible for the formation of the new form lie between nucleotides 910 and 1364. The endogenous polymerase activity of capsids isolated from cells converted the new form into RC DNA. Intracellular capsids containing the new form are secreted inefficiently as virions, in comparison to RC- and DL DNA-containing capsids. Our analysis suggests that the new form is an incomplete RC DNA molecule that is due to a specific block or pause in the synthesis of plus-strand DNA. Our analysis also suggests that capsids become competent for efficient secretion sometime after the synthesis of 1500 nucleotides of plus-strand DNA.
