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| [[Image:1031.jpg|thumb|200px|right|Hepatitis B virus. From [http://www.nlm.nih.gov/medlineplus/ency/imagepages/1031.htm Medline Plus].]] | | [[Category:Short pages]] |
| | {{Curated}} |
| | {{Viral Biorealm Family}} |
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| ==Baltimore Classification== | | ==Baltimore Classification== |
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| ===Higher order taxa=== | | ===Higher order taxa=== |
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| Virus; Hepadnaviridae (Family); Orthohepadnavirus, Avihepadnavirus | | Virus; Retro-transcribing viruses; Hepadnaviridae |
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| ===Species=== | | ===Genera=== |
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| Hepatitis B virus, Duck hepatitis B virus
| | ''Orthohepadnavirus'', ''Avihepadnavirus'' |
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| ==Description and Significance== | | ==Description and Significance== |
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| Also known as serum hepatitis, Hepatitis B spread through blood and sexual sexual contact. It is seen with increased frequency among intravenous drug users who share needles and among the homosexual population. The incubation period is between 45 to 120 days. Hepatitis virus B cannot be cultivated in tissue culture, which has hindered investigations on the virus. Only humans and chimpanzees are susceptible to Hepatitis B virus.
| | The name "Hepadnaviridae" is derived from the Latin word ''hepa'', meaning "liver", due to the liver infections this family of viruses causes. Members of the Hepadnaviridae family are pararetroviruses, and as such are classified with [[Retroviridae|Retroviruses]] and [[Caulimoviridae|Caulimoviruses]] in the genome group of retro-transcribing viruses. [[Hepatitis B virus]], in the genus ''Orthohepadnavirus'', has caused an estimated 350 million chronic cases worldwide. (sources: Pult et al., Aiba et al.) |
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| Hepadnaviruses have the smallest genomes of all known viruses, consisting of two uneven strands of DNA: a (-)sense strand whose size varies between hepadnaciruses and a (+)sense strandwhose size varies between different particles.
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| ==Genome Structure== | | ==Genome Structure== |
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| The genome is -RT, contains a single molecule of circular and is not segmented.The genome is partially double-stranded DNA that forms a covalently closed circle with 5' end of the full lenght minus strand which is linked to the viral DNA polymerase. The complete genome is 3020-3320 nucleotides long (for the full lenght strand) ir 1700-2800 nucleotides long (for the short length strand). The genome has a guanine + cystosine content of 48%. The genome sequence has termini with cohesive ends that match the uniquely located 5'-ends of the two strands which overlap by approximately 240 nucleotides and maintain the circular configuration of the DNA. Complementary to the viral mRNA, the negative-sense or non-coding strand is full length; the viral mRNA, the positive sense strand, is shorter than full-length. The double stranded genome has a nick at a unique site on full length negative strand opposite at a position 242 nucleotides downsream from the 5' end of the positive strand. The 5' end of the negative-sense strand has a covalently attached terminal protein; positive sense strand has a 5' capped oligoribonucleotide pinner. The 3'-terminus has conserved nucleotide sequences; of 1 nucleotide in length. | | The Hepadnaviridae genome is non-segmented and consists of a single molecule of open circular, partially double-stranded DNA containing extensively overlapping genes. The full-length strand of DNA is 3020-3320 nucleotides long, and the short-length strand is 1700-2800 nucleotides long. The genome codes for both structural and non-structural proteins. (source: [http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/30000000.htm ICTVdB], Pult et al.) |
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| ==Virion Structure of a Hepatitis B virus==
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| The virions of Hepatitis B virus are 42nm in diameter and possess an isometric nucleocapsid, the core, of 27nm in diameter, surrounded by an outer coat approximately 4nm thick. The protein of the virion coat is known as "surface antigen" or HBsAg. The surface antigen is sometimes extended as a tubular tail on one side of the virus particle. Produced generally in vast excesses, it is found in the blood of infected individuals in the form of filamentous and spherical particles. Filamentous particles are identical to the virion tails in that they vary in length and have a mean diameter of about 22nm. They sometimes display regular, non-helical transverse striations.
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| ==Reproductive Cycle of a Hepatitis B in a Host Cell==
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| Although a DNA virus, Hepatitis B virus uses a RNA proviral intermediate that has to be copied back to DNA for replication. The copying of RNA to DNA is not a normal function of an uninfected cell but is found in retroviruses that also have an RNA genome and a DNA intermediate that gets integrated into host cell chromosomes. Retroviruses and Hepatitis B virus have a virally-encoded DNA polymerase (P) called reverse transcriptase for copying RNA to DNA.
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| The viral membrane fuses with the cell membrane, releasing the core into the cytoplasm after the Hepatitis B virus has attached to the cell surface receptor, which has yet to be identified. The core proteins dissociate from the partially double stranded DNA. The DNA is now completed with the DNA polymerase providing it the double-strand structure. This is done by the virally-encoded polymerase in the cytoplasm that is one of the core proteins whereas the cell's DNA polymerase is in the nucleus. The double stranded DNA enters the nucleus and the ends are ligated by host enzymes so that the virus is in the form of a circular episome. When the viral DNA associates with host nuclear histones, it is transcribed by cellular RNA polymerase II into mRNAs.The DNA form of Hepatitis B virus is found as an independent episome as opposed to being integrated into cellular DNA, as is the case with retroviruses. This is because hepadnaviruses have no integrase activity. However, integrated parts of the Hepatitis B virus genome are found in the chromosomes of many hepatocellular carcinoma patients.
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| The Hepatitis B genome makes 4 mRNAs. The host cell RNA polymerase interacts with four promoters but transcription always ceases at the same polydenylation site so that the overlaping mRNAs have a common 3' terminus. The polydenylation at one end and a repeated region makes one of these mRNAs slightly longer than the DNA sequence. This is the full length c-RNA that will be the template for the genome. The full length mRNA codes for the polymerase and core HBcAg and HBeAg proteins. The latter are very similar because they are translated in the same reading frame frm two different start codons. Two smaller overlapping mRNAs, 2.4 and 2.1 bases, code for the surface glycoproteins. There is also a small mRNA of 700 bases that codes for a protein that is a protein kinase and is a transactivator of transcription.
| | ==Virion Structure of a Hepadnavirus== |
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| The ful length positive strand c-RNA, 3500 bases, is encapsidatd by core proteins in the cytoplasm. Inside the core, the RNA is transcribed to minus strand DNA by the same DNA polymerase (reverse transcriptase) that completed the double stranded DNA. At the same time, the RNA is degraded by a ribonuclease H that is also part of the reverse transcriptase. The Hepatitis B virus reverse transcription reaction does not require a tRNA primer, unlike the reverse transcriptase of the retroviruses. Rather, the polymerase of te Hepatitis B virus itself acts a a primer and remains covalently attached to the 5' end of the negative strand DNA. Heat shock protein 90, a host cell chaperone protein, is also necessary. the chaperone associates with the reverse transcriptase allowing it to fold into an active conformation.
| | Hepadnaviridae virions consist of an envelope and a nucleocapsid, and are 40-48nm in diameter. The virions are spherical or pleomorphic, although filamentous forms can occur. Spherical forms without cores can also occur. The nucleocapsid is round, exhibits icosahedral symmetry, and is 30-35nm in diameter. The capsid consists of 180 capsomers. (source: [http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/30000000.htm ICTVdB]) |
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| The virus now buds through the endoplasmic reticulum and/or Golgo Body membranes, or perhaps a novel pre-Golgi compartment, of the host cell from which it acquires HBsAg. The minus strand of the DNA is partly transcibed into a plus strand at this stage or later. When the viral DNA polymerase is used to transcribe RNA to DNA, it is acting as a reverse transcriptase similar to that found in retroviruses. In fact, Hepatitis B virus' DNA polymerase and retroviral reverse transcriptase are very similar and may have evolved from a common ancestor.
| | ==Reproduction Cycle of a Hepadnavirus in a Host Cell== |
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| Virus particles that contain RNA or DNA at various stages of replication can be found in the bloodstream, suggesting that nucleic acid replication is not tightly controlled with the passage out of the cell. Furthermore, empty envelopes containing the envelope proteins embedded in a lipid layer are contnually being shed.
| | Replication of all members of this family involves reverse transcription of an RNA intermediate. (source: Pult et al.) |
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| ==Viral Ecology & Pathology== | | ==Viral Ecology & Pathology== |
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| Blood and blood products are the main routes through which Hepatitis B virus is transmitted. In fact, only 0.00004 ml of blood is sufficient for transmission. Any technique that allows the transfer of blood or serum from one individual to another is potentially likely to transmit Hepatitis B virus. Hepatitis B infection is especially common amongst IV drug abusers, Many cases occured following blood transfusion before the advent of screening. It is also particularly common amongst homosexuals where the practice of anal intercourse is particularly traumatic and frequently results in bleeding. Acupuncture, tatooing and ear piercing have also led to many reported cases of Hepatitis B infection. Hepatitis B is a known occupational hazard and the risk to health workers following accidental innoculation is 6-20%. Health personnel in renal dialysis units are particularly vulnerable.
| | Hepadnaviruses infect a wide variety of species, causing liver infections. In humans, [[Hepatitis B virus]] causes new infections in nearly 60,000 people per year. Hepadnaviruses also infect rodents such as woodchucks and squirrels, old and new world primates such as wooly monkeys and gibbons, and in birds (most notably in ducks, but also in gray herons and snow geese). (sources: [http://www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm CDC], Pult et al.) |
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| It has become clear that Hepatitis B virus is not spread exclusively by blood and blood products. The virus is infective by mouth under certain circumstances. It is endemic in mentally handicapped homes, prisons and other such closed institutions. The virus is also found in semen, vaginal discharge, breast milk and serous exudates such as the CSF and these have been implicated as possible vehicles of transmission. The presence of Hepatitis B virus has also been reported in urine, faeces, bile, sweat and tears but has not been confirmed yet. The membranes of the eye or mouth could also be possible routes of transmission of the virus. All biological fluids from a Hepatitis B infected individual must be treated as potentially infectious. Although HBsAg has been detected in mosquitoes and bed bugs, there is little evience to suggest the possibility for replication of the virus in these insects.Although mechanical transmission of infection must be a possibility, the role of anthropod vectors is uncertain.
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| Hepatitis B virus B infection does not appear to be related to genetic factors and does not reflect maternal or veneral transmission, although clustering does occur withing family groups. The virus does not normally infect the fetus but the baby is at risk of infection during birth.The risk of transmission to the fetus may reach 50-60%, though it varies from country to country and appears to be related to ethnic groups. The risk of perinatal infection is substantial if the mother had acute hepatitis B in the second or thrid trimester of pregnancy or within two months of delivery. The mechanism of perinatal transmission is uncertain but it probably occurs during or shortly after birth as a result of a leak of maternal blood into the baby's circulation or of its ingestion or inadvertent inoculation. Most children infected during the perinatal period become persistent carriers. 70 - 90% of infants born to e +ve mothers become carriers.
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| Hepatitis B infection is found worldwide but the prevalence varies enormously between different countries. Estimates suggest that one-half of the world population has experienced infection and there are 350 million chronically infected individuals. Hepatitis B is responsible for 1.5 million deaths every year. Around 40% of chronically infected individuals die as a result of their infection. The mechanism for maintaining the high prevalence rate in some countrues appears to be the high carrier rate and the rate of high prinatal infection. Infection in infancy is very common, particularly acquired from the carrier mothers at birth, in high prevalence areas. The possibility for someone to be a persistent carrier is greater if the infection occured earlier in life. The result is that the carrier rate in the adult population is 10 - 20 % and almost all the remainder of the population is immune. Infection is also common in childhood but is usually horizontal between children in areas of intermediate prevalence. African Hepatitis B virus carrier mothers are less likely to be e +ve than thier Oriental counterpartsand thus less likely to transfer Hepatitis B virus perinatally. The carrier rate in adults is 2 - 10 % and a quarter to half the population is immune. Infection is rare in childhood in low prevalence areas, the carrier rate is low (0.1 - 0.5%), with a low prevalence of natural immunity in the general population being in the order of 2 - 6%.
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| The infected hepatocytes are charecteristically enlarged and their cytoplasm has a ground glass appearance. HBsAg is found associated with the endoplasmic reticulum and the cell nuclei has core particles containing HBcAg. It has been pistulated that liver injury may result from immune mchanism due to larger antigenic load present in hepatcytes and in the serum. Necrosis of hepatocytes results in scattered focal inflammatory response with macrophage and lymphocyte infiltrations together with portal inflamation and endophlebitis of the central veins. In severe cases, lines of necrosis extends from the portal tracts to the central veins and this often precedes chronic hepatitis and cirrhosis. Asymptomatic carriers may either have normal liver histology or may show chronic liver inflammation that is recognized as chornic persisten hepatitis. This normally resolves within months or years of acute infection. Some may develop chronic periportal hepatitis which correlates clinically with chronic active hepatitis and continuing patchy necrosis with fibrosis likely to lead to major disruption in liver architecture characteristic of cirrhosis. It takes around 4 to 5 years for cirrhosis to develop. Some carriers may go on to develop hepatocellular carcinoma.
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| ==References. Updated June 6, 2006==
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| [http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/ Medline Plus] | |
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| [http://www.ncbi.nlm.nih.gov/ National Center for Biotechnology Information]
| | ==References== |
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| [http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/ ICTVdb Descriptions]
| | Aiba et al. "Complete Nucleotide Sequence and Phylogenetic Analyses of Hepatitis B Virus Isolated from Two Pileated Gibbons." ''Virus Genes'' 27.3 (2003): 219-226. |
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| [http://web.uct.ac.za/depts/mmi/stannard/emimages.html Electron Micrograph Images: Virus Ultra Structure] | | [http://www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm Centers for Disease Control and Prevention. Viral Hepatitis B Fact Sheet.] |
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| [http://pathmicro.med.sc.edu/virol/hepatitis-virus.htm Microbiology and Immunology Online: University of South Carolina] | | [http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/30000000.htm ICTVdB - The Universal Virus Database, version 3. http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/] |
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| [http://www.faqs.org/health/Sick-V2/Hepatitis.html Wong's Virology]
| | Pult et al. "Identification and Analysis of a New Hepadnavirus in White Storks." ''Virology'' 289.1 (2001): 114-128. |
A Viral Biorealm page on the family Hepadnaviridae
Baltimore Classification
Higher order taxa
Virus; Retro-transcribing viruses; Hepadnaviridae
Genera
Orthohepadnavirus, Avihepadnavirus
Description and Significance
The name "Hepadnaviridae" is derived from the Latin word hepa, meaning "liver", due to the liver infections this family of viruses causes. Members of the Hepadnaviridae family are pararetroviruses, and as such are classified with Retroviruses and Caulimoviruses in the genome group of retro-transcribing viruses. Hepatitis B virus, in the genus Orthohepadnavirus, has caused an estimated 350 million chronic cases worldwide. (sources: Pult et al., Aiba et al.)
Genome Structure
The Hepadnaviridae genome is non-segmented and consists of a single molecule of open circular, partially double-stranded DNA containing extensively overlapping genes. The full-length strand of DNA is 3020-3320 nucleotides long, and the short-length strand is 1700-2800 nucleotides long. The genome codes for both structural and non-structural proteins. (source: ICTVdB, Pult et al.)
Virion Structure of a Hepadnavirus
Hepadnaviridae virions consist of an envelope and a nucleocapsid, and are 40-48nm in diameter. The virions are spherical or pleomorphic, although filamentous forms can occur. Spherical forms without cores can also occur. The nucleocapsid is round, exhibits icosahedral symmetry, and is 30-35nm in diameter. The capsid consists of 180 capsomers. (source: ICTVdB)
Reproduction Cycle of a Hepadnavirus in a Host Cell
Replication of all members of this family involves reverse transcription of an RNA intermediate. (source: Pult et al.)
Viral Ecology & Pathology
Hepadnaviruses infect a wide variety of species, causing liver infections. In humans, Hepatitis B virus causes new infections in nearly 60,000 people per year. Hepadnaviruses also infect rodents such as woodchucks and squirrels, old and new world primates such as wooly monkeys and gibbons, and in birds (most notably in ducks, but also in gray herons and snow geese). (sources: CDC, Pult et al.)
References
Aiba et al. "Complete Nucleotide Sequence and Phylogenetic Analyses of Hepatitis B Virus Isolated from Two Pileated Gibbons." Virus Genes 27.3 (2003): 219-226.
Centers for Disease Control and Prevention. Viral Hepatitis B Fact Sheet.
ICTVdB - The Universal Virus Database, version 3. http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/
Pult et al. "Identification and Analysis of a New Hepadnavirus in White Storks." Virology 289.1 (2001): 114-128.
