Hepadnaviridae

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/10 17:16:02」(JST)

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Hepadnaviridae
TEM micrograph showing hepatitis B virions
Virus classification
Group:	Group VII (dsDNA-RT)
Order:	Unassigned
Family:	Hepadnaviridae
Genera
Orthohepadnavirus Avihepadnavirus

Hepadnaviridae is a family of viruses. Humans, apes, and birds serve as natural hosts. There are currently seven species in this family, divided among 2 genera. Its most well-known member is the Hepatitis B virus. Diseases associated with this family include: liver infections, such as hepatitis, hepatocellular carcinomas (chronic infections), and cirrhosis.

Taxonomy

Group: dsDNA-RT

Order: Unassigned

• Family: Hepadnaviridae

  • Genus: Avihepadnavirus 

    • Duck hepatitis B virus
    • Heron hepatitis B virus
  • Genus: Orthohepadnavirus 

    • Bat hepatitis virus
    • Ground squirrel hepatitis virus
    • Hepatitis B virus
    • Woodchuck hepatitis virus
    • Woolly monkey hepatitis B virus

Etymology

The name of the family comes from hepa(for HEPAtic)-DNA-virus. "Hepad" means "liver" and is a reference to the family's primary human-pathogenic virus: Hepatitis B Virus.

History and Discovery

Although liver diseases transmissible among human populations were identified early in documented medical history, the first known hepatitis with a viral etiological agent was Hepatitis A in the Picornaviridae family. Hepatits B Virus (HBV) was identified as an infection distinct from Hepatitis A through its contamination of measles, mumps, and yellow fever vaccines in the 1930s and 40s. These vaccines contained HBV-infected human serum as a stabilizing agent. HBV was identified as a new DNA virus in the 1960s, followed only a few decades later by the discovery of the Flavivirus Hepatitis C. HBV was first identified in the lab as the "Australia agent" by Blumberg and colleagues in the blood of an Aboriginal transfusion patient. This work earned Blumberg the 1976 Nobel Prize in Medicine.

Genome

Hepadnaviruses have very small genomes of partially double-stranded, partially single stranded circular DNA. The genome consists of two strands, a longer negative-sense strand and a shorter and positive-sense strand of variable length. In the virion these strands are arranged such that the two ends of the long strand meet but are not covalently bonded together. The shorter strand overlaps this divide and is connected to the longer strand on either side of the split through a direct repeat (DR) segment that pairs the two strands together. In replication, this pds genome is converted in the host cell nucleus to covalently-closed-circular DNA (cccDNA) by the viral polymerase.

As it is a group 7 virus, replication involves an RNA intermediate. Four main open reading frames are encoded (ORFs) and the virus has four known genes which encode seven proteins: the capsid protein, the viral polymerase, surface antigens—preS1, preS2, and S, the X protein and HBsEAg. The X protein is thought to be non-structural. Its function and significance are poorly understood but it is suspected to be associated with host gene expression modulation.

Viral Polymerase

Hepadnaviridae encode their own polymerase, rather than co-opting host machinery as some other viruses do. This enzyme is unique among viral polymerases in that it has reverse transcriptase activity to convert RNA into DNA to replicate the genome (the only other human-pathogenic virus family encoding a polymerase with this capability is Retroviridae), RNAse activity (used when the DNA genome is synthesized from pgRNA that was packaged in virions for replication to destroy the RNA template and produce the pdsDNA genome), and DNA-dependent-DNA-polymerase activity (used to create cccDNA from pdsDNA in the first step of the replication cycle).

Envelope Proteins

The hepatitis envelope proteins are composed of subunits made from the viral preS1, preS2, and S genes. The L (for "large") envelope protein contains all three subunits. The M (for "medium") protein contains only preS2 and S. The S (for "small") protein contains only S. The genome portions encoding these envelope protein subuntis share both the same frame and the same stop codon (generating nested transcripts on a single open reading frame. The pre-S1 is encoded first (closest to the 5' end), followed directly by the pre-S2 and the S. When a transcript is made from the beginning of the pre-S1 region, all three genes are included in the transcript and the L protein is produced. When the transcript starts after the pro-S1 at the beginning of the pre-S2 the final protein contains the pre-S2 and S subunits only and therefore is an M protein. The smallest envelope protein containing just the S subunit is made most because it is encoded closest to the 3' end and comes from the shortest transcript. These envelope proteins can assemble independently of the viral capsid and genome into non-infectious virus-like particles that give the virus a pleomorphic appearance and promote a strong immune response in hosts.

Replication

Hepadnaviruses replicate through an RNA intermediate (which they transcribe back into cDNA using reverse transcriptase). The reverse transcriptase becomes covalently linked to a short 3- or 4-nucleotide primer. Most hepadnaviruses will only replicate in specific hosts, and this makes experiments using in vitro methods very difficult.

The virus binds to specific receptors on cells and the core particle enters the cell cytoplasm. This is then translocated to the nucleus, where the partially double stranded DNA is 'repaired' by the viral polymerase to form a complete circular dsDNA genome (called covalently-closed-circular DNA or cccDNA). The genome then undergoes transcription by the host cell RNA polymerase and the pregenomicRNA (pgRNA) is sent out of the nucleus. The pgRNA is inserted into an assembled viral capsid containing the viral polymerase. Inside this capsid the genome is converted from RNA to pdsDNA through activity of the polymerase as an RNA-dependent-DNA-polymerase and subsequently as an RNAse to eliminate the pgRNA transcript. These new virions either leave the cell to infect others or are immediately dismantled so the new viral genomes can enter the nucleus and magnify the infection. The virions that leave the cell egress through budding.

Genus	Host Details	Tissue Tropism	Entry Details	Release Details	Replication Site	Assembly Site	Transmission
Avihepadnavirus	Birds	Hepatocytes	Cell receptor endocytosis	Budding	Nucleus	Cytoplasm	Vertical: parental; sex; blood
Orthohepadnavirus	Humans; mammals	Hepatocytes	Cell receptor endocytosis	Budding	Nucleus	Cytoplasm	Vertical: parental; sex; blood

Structure

Viruses in Hepadnaviridae are enveloped, with spherical geometries, and T=4 symmetry. The diameter is around 42 nm. Genomes are circular, around 3.2kb in length. The genome codes for 7 proteins.

Genus	Structure	Symmetry	Capsid	Genomic Arrangement	Genomic Segmentation
Avihepadnavirus	Icosahedral	T=4	Non-Enveloped	Circular	Monopartite
Orthohepadnavirus	Icosahedral	T=4	Non-Enveloped	Circular	Monopartite

Evolution

Based on the presence of viral genomes in bird DNA it appears that the Hepatoviruses evolved >82 million years ago. Birds may be the original hosts of the Hepatovirus with mammals becoming infected after a bird -> mammal host shift.

Cell Tropism

Hepadnaviruses, as their "hepa" name implies, infect liver cells and cause hepatitis. This is true not only of the human pathogen Hepatitis B Virus but also the hepadnaviruses that infect other organisms. The "adhesion" step of the dynamic phase—in which an exterior viral protein stably interacts with a host cell protein—determines cell tropism. In the case of HBV the host receptor is human sodium taurocholate receptor (NTCP), a mediator of bile acid uptake, and the virus anti-receptor is the abundant HB-AgS envelope protein.

References

External links

• Viralzone: Hepadnaviridae
• ICTV

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 肝炎ウイルスと新生児：臨床症状および治療 hepatitis viruses and the newborn clinical manifestations and treatment
• 2. 一般的なB型肝炎ウイルス亜種の臨床的意義および分子学的特徴 clinical significance and molecular characteristics of common hepatitis b virus variants
• 3. B型肝炎ウイルス遺伝子型の臨床的意義 clinical significance of hepatitis b virus genotypes

English Journal

• Viral infections of the folds (intertriginous areas).

• Adışen E1, Önder M2.
• Clinics in dermatology.Clin Dermatol.2015 Jul-Aug;33(4):429-36. doi: 10.1016/j.clindermatol.2015.04.004. Epub 2015 Apr 8.
• Viruses are considered intracellular obligates with a nucleic acid, either RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of t
• PMID 26051057

• Identification of BST-2/tetherin-induced hepatitis B virus restriction and hepatocyte-specific BST-2 inactivation.

• Lv M1, Zhang B2, Shi Y3, Han Z3, Zhang Y4, Zhou Y5, Zhang W3, Niu J6, Yu XF7.
• Scientific reports.Sci Rep.2015 Jun 29;5:11736. doi: 10.1038/srep11736.
• BST-2/tetherin is an interferon-inducible antiviral protein that blocks the release of various enveloped viruses, including HIV-1. Hepatitis B virus (HBV), a major cause of liver disease, belongs to the Hepadnaviridae family of enveloped DNA viruses. Whether BST-2 regulates HBV production is largely
• PMID 26119070

• Applications of human hepatitis B virus preS domain in bio- and nanotechnology.

• Toita R1, Kawano T1, Kang JH1, Murata M1.
• World journal of gastroenterology : WJG.World J Gastroenterol.2015 Jun 28;21(24):7400-11. doi: 10.3748/wjg.v21.i24.7400.
• Human hepatitis B virus (HBV) is a member of the family Hepadnaviridae, and causes acute and chronic infections of the liver. The hepatitis B surface antigen (HBsAg) contains the large (L), middle (M), and small (S) surface proteins. The L protein consists of the S protein, preS1, and preS2. In HBsA
• PMID 26139986

Related Links

• Hepadnaviridae - definition of Hepadnaviridae by Medical ...

Hepadnaviridae /Hep·ad·na·vi·ri·dae/ (hep-ad″nah-vir´ĭ-de) the hepatitis B–like viruses: a family of DNA viruses causing infection and associated with chronic disease and neoplasia. Hepadnaviridae (hepad″nəvir´-ô idē), n one of the major ...

• Hepadnaviridae - Bio-Medicine - latest biology and medical ...

... navigation, search. Hepadnaviridae. Micrograph showing ... Hepadnaviridae · Caulimoviridae. Retrieved from "http://en.wikipedia.org /wiki/ Hepadnaviridae" ... Full article >>> The name "Hepadnaviridae" is derived from the Latin word ...

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ヘパドナウイルス感染症