Hepadnaviridae

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Hepadnaviridae
Hepatitis B virus 1.jpg
TEM micrograph showing Hepatitis B virus virions
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Blubervirales
Family:Hepadnaviridae
Genera [1]

Hepadnaviridae [lower-alpha 1] is a family of viruses. [2] Humans, apes, and birds serve as natural hosts. There are currently 18 species in this family, divided among 5 genera. [3] Its best-known member is hepatitis B virus. Diseases associated with this family include: liver infections, such as hepatitis, hepatocellular carcinomas (chronic infections), and cirrhosis. [3] [4] It is the sole accepted family in the order Blubervirales.

Contents

Taxonomy

The following genera are recognized:[ citation needed ]

History and discovery

Although liver diseases transmissible among human populations were identified early in the history of medicine, the first known hepatitis with a viral etiological agent was Hepatitis A, in the picornaviridae family. Hepatitis B Virus (HBV) was identified as an infection distinct from Hepatitis A through its contamination of Yellow_fever_vaccine#History. The vaccine contained human serum as a stabilizing agent which was HBV-infected. [5] HBV was identified as a new DNA virus in the 1960s, followed a couple of 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.[ citation needed ]

Genome

The genome organisation of HBV; the genes overlap HBV Genome.svg
The genome organisation of HBV; the genes overlap

Hepadnaviruses have very small genomes of partially double-stranded, partially single stranded circular DNA (pdsDNA). 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, the viral pdsDNA is converted in the host cell nucleus to covalently-closed-circular DNA (cccDNA) by the viral polymerase.[ citation needed ]

Replication involves an RNA intermediate, as in viruses belonging to group VII of Baltimore classification. Four main open reading frames are encoded (ORFs) and the virus has four known genes which encode seven proteins: the core capsid protein, the viral polymerase, surface antigens—preS1, preS2, and S, the X protein and HBeAg. 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.[ citation needed ]

Viral polymerase

Members of the family 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).[ citation needed ]

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 subunits 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.[ citation needed ]

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. [6] 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.[ citation needed ]

GenusHost detailsTissue tropismEntry detailsRelease detailsReplication siteAssembly siteTransmission
AvihepadnavirusBirdsHepatocytesCell receptor endocytosisBuddingNucleusCytoplasmVertical: parental; sex; blood
OrthohepadnavirusHumans; mammalsHepatocytesCell receptor endocytosisBuddingNucleusCytoplasmVertical: 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. [3] [4]

GenusStructureSymmetryCapsidGenomic arrangementGenomic segmentation
AvihepadnavirusIcosahedralT=4EnvelopedCircularMonopartite
OrthohepadnavirusIcosahedralT=4EnvelopedCircularMonopartite

Evolution

Based on the presence of viral genomes in bird DNA it appears that the hepadnaviruses evolved > 82  million years ago. [7] Birds may be the original hosts of the Hepadnaviridae with mammals becoming infected after a bird (see host switch).

Endogenous hepatitis B virus genomes have been described in crocodilian, snake and turtle genomes. [8] This suggests that these viruses have infected vertebrates for over 200  million years ago.[ citation needed ]

Hepadnaviruses have been described in fish and amphibians also. [9] This suggests that this family has co-evolved with the vertebrates.[ citation needed ]

Phylogenetic trees suggest that the bird viruses originated from those infecting reptiles. Those affecting mammals appear to be more closely related to those found in fish. [10]

Nackednaviridae

A proposed family of viruses – the Nackednaviridae – has been isolated from fish. This family has a similar genomic organisation to that of members of the family Hepadnaviridae. These two families separated over 400  million years ago, suggesting an ancient origin for the family Hepadnaviridae. [10]

Viruses in the family have non-enveloped, isosahedral structure with T=3 symmetry, smaller than typical Hepadnaviridae virions (about 5% of the latter show a T=3 symmetry). The circular, monopartite genome is about 3 kb much like Hepadnaviridae. The envelop protein S is accordingly not present, likely the ancestral state by sequence analysis. Unlike Hepadnaviridae viruses that usually diverge alongside their hosts, viruses in the family jump hosts more frequently. [10] The "type" for this family is African cichlid nackednavirus (ACNDV), formerly African cichlid hepadnavirus (ACHBV), a proposed and not-yet-accepted species. [9]

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. [11]

See also

Notes

  1. Etymology – portmanteau of hepa (liver: reference to Hepatitis B the primary human member) DNA virus.

Related Research Articles

<span class="mw-page-title-main">DNA virus</span> Virus that has DNA as its genetic material

A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and those that have one strand of DNA in their genome, called single-stranded DNA (ssDNA) viruses. dsDNA viruses primarily belong to two realms: Duplodnaviria and Varidnaviria, and ssDNA viruses are almost exclusively assigned to the realm Monodnaviria, which also includes some dsDNA viruses. Additionally, many DNA viruses are unassigned to higher taxa. Reverse transcribing viruses, which have a DNA genome that is replicated through an RNA intermediate by a reverse transcriptase, are classified into the kingdom Pararnavirae in the realm Riboviria.

<span class="mw-page-title-main">Retrovirus</span> Family of viruses

A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.

Virus classification is the process of naming viruses and placing them into a taxonomic system similar to the classification systems used for cellular organisms.

<i>Parvoviridae</i> Family of viruses

Parvoviruses are a family of animal viruses that constitute the family Parvoviridae. They have linear, single-stranded DNA (ssDNA) genomes that typically contain two genes encoding for a replication initiator protein, called NS1, and the protein the viral capsid is made of. The coding portion of the genome is flanked by telomeres at each end that form into hairpin loops that are important during replication. Parvovirus virions are small compared to most viruses, at 23–28 nanometers in diameter, and contain the genome enclosed in an icosahedral capsid that has a rugged surface.

<span class="mw-page-title-main">Rubella virus</span> Species of virus

Rubella virus (RuV) is the pathogenic agent of the disease rubella, transmitted only between humans via the respiratory route, and is the main cause of congenital rubella syndrome when infection occurs during the first weeks of pregnancy.

<i>Geminiviridae</i> Family of viruses

Geminiviridae is a family of plant viruses that encode their genetic information on a circular genome of single-stranded (ss) DNA. There are 520 species in this family, assigned to 14 genera. Diseases associated with this family include: bright yellow mosaic, yellow mosaic, yellow mottle, leaf curling, stunting, streaks, reduced yields. They have single-stranded circular DNA genomes encoding genes that diverge in both directions from a virion strand origin of replication. According to the Baltimore classification they are considered class II viruses. It is the largest known family of single stranded DNA viruses.

Pseudoviridae is a family of viruses, which includes three genera.

<span class="mw-page-title-main">Viral replication</span> Formation of biological viruses during the infection process

Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm.

Baltimore classification is a system used to classify viruses based on their manner of messenger RNA (mRNA) synthesis. By organizing viruses based on their manner of mRNA production, it is possible to study viruses that behave similarly as a distinct group. Seven Baltimore groups are described that take into consideration whether the viral genome is made of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), whether the genome is single- or double-stranded, and whether the sense of a single-stranded RNA genome is positive or negative.

<i>Iridoviridae</i> Family of viruses

Iridoviridae is a family of viruses with double-stranded DNA genomes. Amphibians, fish, and invertebrates such as arthropods serve as natural hosts. There are currently 22 species in this family, divided among two subfamilies and seven genera.

<i>Hepatitis B virus</i> Species of the genus Orthohepadnavirus

Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B.

The transmission of hepadnaviruses between their natural hosts, humans, non-human primates, and birds, including intra-species host transmission and cross-species transmission, is a topic of study in virology.

Plectrovirus is a genus of viruses, in the family Plectroviridae. Bacteria in the phylum Mycoplasmatota serve as natural hosts, making these viruses bacteriophages. Acholeplasma virus L51 is the only species in the genus.

Spiraviridae is a family of incertae sedis viruses that replicate in hyperthermophilic archaea of the genus Aeropyrum, specifically Aeropyrum pernix. The family contains one genus, Alphaspiravirus, which contains one species, Aeropyrum coil-shaped virus. The virions of ACV are non-enveloped and in the shape of hollow cylinders that are formed by a coiling fiber that consists of two intertwining halves of the circular DNA strand inside a capsid. An appendage protrudes from each end of the cylindrical virion. The viral genome is ssDNA(+) and encodes for significantly more genes than other known ssDNA viruses. ACV is also unique in that it appears to lack its own enzymes to aid replication, instead likely using the host cell's replisomes. ACV has no known relation to any other archaea-infecting viruses, but it does share its coil-like morphology with some other archaeal viruses, suggesting that such viruses may be an ancient lineage that only infect archaea.

<i>Avian metaavulavirus 2</i> Species of virus

Avian metaavulavirus 2, formerly Avian paramyxovirus 2, is a species of virus belonging to the family Paramyxoviridae and genus Metaavulavirus. The virus is a negative strand RNA virus containing a monopartite genome. Avian metaavulavirus 2 is one of nine species belonging to the genus Metaavulavirus. The most common serotype of Avulavirinae is serotype 1, the cause of Newcastle disease (ND). Avian metaavulavirus 2 has been known to cause disease, specifically mild respiratory infections in domestic poultry, including turkeys and chickens, and has many economic effects on egg production and poultry industries. The virus was first isolated from a strain in Yucaipa, California in 1956. Since then, other isolates of the virus have been isolated worldwide.

<i>Ground squirrel hepatitis virus</i> Species of virus

Ground squirrel hepatitis virus, abbreviated GSHV, is a partially double-stranded DNA virus that is closely related to human Hepatitis B virus (HBV) and Woodchuck hepatitis virus (WHV). It is a member of the family of viruses Hepadnaviridae and the genus Orthohepadnavirus. Like the other members of its family, GSHV has high degree of species and tissue specificity. It was discovered in Beechey ground squirrels, Spermophilus beecheyi, but also infects Arctic ground squirrels, Spermophilus parryi. Commonalities between GSHV and HBV include morphology, DNA polymerase activity in genome repair, cross-reacting viral antigens, and the resulting persistent infection with viral antigen in the blood (antigenemia). As a result, GSHV is used as an experimental model for HBV.

<i>Woolly monkey hepatitis B virus</i> Species of virus

The woolly monkey hepatitis B virus (WMHBV) is a viral species of the Orthohepadnavirus genus of the Hepadnaviridae family. Its natural host is the woolly monkey (Lagothrix), an inhabitant of South America categorized as a New World primate. WMHBV, like other hepatitis viruses, infects the hepatocytes, or liver cells, of its host organism. It can cause hepatitis, liver necrosis, cirrhosis, and hepatocellular carcinoma. Because nearly all species of Lagothrix are threatened or endangered, researching and developing a vaccine and/or treatment for WMHBV is important for the protection of the whole woolly monkey genus.

<i>Monodnaviria</i> Realm of viruses

Monodnaviria is a realm of viruses that includes all single-stranded DNA viruses that encode an endonuclease of the HUH superfamily that initiates rolling circle replication of the circular viral genome. Viruses descended from such viruses are also included in the realm, including certain linear single-stranded DNA (ssDNA) viruses and circular double-stranded DNA (dsDNA) viruses. These atypical members typically replicate through means other than rolling circle replication.

<i>Orthornavirae</i> Kingdom of viruses

Orthornavirae is a kingdom of viruses that have genomes made of ribonucleic acid (RNA), including genes which encode an RNA-dependent RNA polymerase (RdRp). The RdRp is used to transcribe the viral RNA genome into messenger RNA (mRNA) and to replicate the genome. Viruses in this kingdom share a number of characteristics which promote rapid evolution, including high rates of genetic mutation, recombination, and reassortment.

<i>Botourmiaviridae</i> Family of viruses

Botourmiaviridae is a family of positive-strand RNA viruses which infect plants and fungi. The family includes four genera: Ourmiavirus, Botoulivirus, Magoulivirus and Scleroulivirus. Members of genus Ourmiavirus infect plants and the other genera infect fungi. The member viruses have genomes which range from 2900 to 4800 nucleotides.

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