Hepatitis C virus
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2008-07-11T20:02:56Z
Prabbit
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/* Genome */
{{Taxobox
| name = Hepatitis C virus
| image = Em_flavavirus-HCV_samp1c.jpg
| image_width = 160px
| image_caption = Electron micrograph of Hepatitis C virus. The bar = 50 nm
| virus_group = iv
| familia = [[Flaviviridae]]
| genus = ''[[Hepacivirus]]''
| type_species = '''''Hepatitis C virus'''''
}}
:''This page is for the virus. For the disease, see [[Hepatitis C]].''
'''Hepatitis C virus''' ('''HCV''') is a small (50 [[metre#SI prefixes|nm]] in size), enveloped, [[Sense (molecular biology)#Positive-sense|positive sense]] single strand [[RNA]] virus in the family ''[[Flaviviridae]]''. Although [[Hepatitis A virus]], [[Hepatitis B virus]], and Hepatitis C virus have similar names (because they all cause [[liver]] inflammation), these are distinctly different viruses both genetically and clinically.
==Structure==
[[Image:HCV structure.png|left|thumb|300px|Simplified diagram of the structure of the Hepatitis C virus particle]]
The structure of the hepatitis C virus consists of a core of genetic material (RNA), surrounded by an [[Truncated icosahedron|icosahedral]] protective shell of [[protein]], and further encased in a lipid (fatty) envelope of cellular origin. Two viral envelope [[glycoprotein]]s, E1 and E2, are embedded in the lipid envelope.<ref name="pmid12820185">{{cite journal
|author=Op De Beeck A, Dubuisson J
|title=Topology of hepatitis C virus envelope glycoproteins
|journal=Rev. Med. Virol.
|volume=13
|issue=4
|pages=233–41
|year=2003
|pmid=12820185
|doi=10.1002/rmv.391
}}</ref>
==Genome==
[[Image:HCV genome.png|left|thumb|300px|Genome organisation of Hepatitis C virus]]
Hepatitis C virus has a positive sense [[RNA]] [[genome]] that consists of a single [[open reading frame]] of 9600 [[nucleoside]] bases.<ref name="pmid11252351">{{cite journal |author=Kato N |title=Genome of human hepatitis C virus (HCV): gene organization, sequence diversity, and variation |journal=Microb. Comp. Genomics |volume=5 |issue=3 |pages=129–51 |year=2000 |pmid=11252351 |doi=}}</ref> At the 5’ and 3’ ends of the RNA are the UTR regions, that are not translated into proteins but are important to translation and replication of the viral RNA. The 5’ UTR has a [[ribosome]] binding site<ref name="pmid11497352">{{cite journal |author=Jubin R |title=Hepatitis C IRES: translating translation into a therapeutic target |journal=Curr. Opin. Mol. Ther. |volume=3 |issue=3 |pages=278–87 |year=2001 |pmid=11497352 |doi=}}</ref> (IRES - Internal Ribosomal Entry Site) that starts the translation of a 3000 amino acid containing protein that is later cut by cellular and viral [[protease]]s into 10 active structural and non-structural smaller proteins.<ref name="pmid17552023">{{cite journal |author=Dubuisson J |title=Hepatitis C virus proteins |journal=World J. Gastroenterol. |volume=13 |issue=17 |pages=2406–15 |year=2007 |pmid=17552023 |doi=}}</ref>
==Replication==
[[Image:HepC replication.png|left|thumb|300px|A simplified diagram of the HCV replication cycle]]
Replication of HCV involves several steps. The viruses need a certain environment to be able to replicate, and must therefore first move to such areas.
HCV has a high rate of replication with approximately one trillion particles produced each day in an infected individual. Due to lack of proofreading by the HCV RNA polymerase, HCV also has an exceptionally high mutation rate, a factor that may help it elude the host's immune response.
HCV mainly replicates within [[hepatocyte]]s in the liver, although there is controversial evidence for replication in [[lymphocyte]]s or [[monocyte]]s. By mechanisms of [[host tropism]], the viruses reach these proper locations. Circulating HCV particles bind to [[receptor (biochemistry)|receptors]] on the surfaces of hepatocytes and subsequently enter the cells. Two putative HCV receptors are [[CD81]] and human [[scavenger receptor class B1]] (SR-BI). However, these receptors are found throughout the body. The identification of hepatocyte-specific cofactors that determine observed HCV liver [[tropism]] are currently under investigation.
Once inside the hepatocyte, HCV initiates the [[lytic cycle]]. It utilizes the intracellular machinery necessary to accomplish its own replication.<ref name="lindenbach">{{cite journal | author = Lindenbach B, Rice C | title = Unravelling hepatitis C virus replication from genome to function | journal = Nature | volume = 436 | issue = 7053 | pages = 933–8 | year = 2005 | pmid = 16107832 | doi = 10.1038/nature04077}}</ref>
Specifically, the HCV genome is [[translation (biology)|translated]] to produce a single protein of around 3011 amino acids. This "polyprotein" is then proteolytically processed by viral and cellular [[proteases]] to produce three structural (virion-associated) and seven nonstructural (NS) proteins. Alternatively, a frameshift may occur in the Core region to produce an Alternate Reading Frame Protein (ARFP). HCV encodes two proteases, the NS2 cysteine autoprotease and the NS3-4A serine protease. The NS proteins then recruit the viral genome into an RNA replication complex, which is associated with rearranged cytoplasmic membranes. RNA replication takes places via the viral RNA-dependent [[RNA polymerase]] of NS5B, which produces a negative-strand RNA intermediate. The negative strand RNA then serves as a template for the production of new positive-strand viral genomes. Nascent genomes can then be translated, further replicated, or packaged within new virus particles. New virus particles presumably bud into the secretory pathway and are released at the cell surface.
==Genotypes==
Based on genetic differences between HCV isolates, the hepatitis C virus species is classified into six [[genotypes]] (1-6) with several subtypes within each genotype (represented by letters). Subtypes are further broken down into quasispecies based on their genetic diversity. The preponderance and distribution of HCV genotypes varies globally. For example, in [[North America]], genotype 1a predominates followed by 1b, 2a, 2b, and 3a. In [[Europe]], genotype 1b is predominant followed by 2a, 2b, 2c, and 3a. Genotypes 4 and 5 are found almost exclusively in [[Africa]]. Genotype is clinically important in determining potential response to [[interferon]]-based therapy and the required duration of such therapy. Genotypes 1 and 4 are less responsive to [[interferon]]-based treatment than are the other genotypes (2, 3, 5 and 6).<!--
--><ref name="simmonds">{{cite journal | author = Simmonds P, Bukh J, Combet C, Deléage G, Enomoto N, Feinstone S, Halfon P, Inchauspé G, Kuiken C, Maertens G, Mizokami M, Murphy D, Okamoto H, Pawlotsky J, Penin F, Sablon E, Shin-I T, Stuyver L, Thiel H, Viazov S, Weiner A, Widell A | title = Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes | journal = Hepatology | volume = 42 | issue = 4 | pages = 962–73 | year = 2005 | pmid = 16149085 | doi = 10.1002/hep.20819}}</ref>
Duration of standard interferon-based therapy for genotypes 1 and 4 is 48 weeks, whereas treatment for genotypes 2 and 3 is completed in 24 weeks.
==Vaccination==
Unlike hepatitis A and B, there is currently no [[vaccine]] to prevent hepatitis C infection.
In a 2006 study, 60 patients received four different doses of an experimental hepatitis C vaccine. All the patients produced [[antibodies]] that the researchers believe could protect them from the virus.<!--
--><ref name="KGO-TV-HepcVaccine">{{cite news | first=Dean | last=Edell | url=http://abclocal.go.com/kgo/story?section=edell&id=4278043 | title=Hepatitis C Vaccine Looks Promising | publisher=ABC7/KGO-TV | date =2006 | accessdate =2006-07-04}}</ref>
==Current Research==
In 2007 the World Community Grid launched a project where, by computer modeling of the Hepatitis C Virus (and related viruses), thousands of small molecules are screened for their potential anti-viral properties in fighting the Hepatitis C Virus. This is the first project to seek out medicines to directly attack the virus once a person is infected. This is a distributed process project similar to [[SETI@Home]] where the general public downloads the World Community Grid agent and the program (along with thousands of other users) screens thousands of molecules while their computer would be otherwise idle. If the user needs to use the computer the program sleeps. There are several different projects running, including a similar one screening for anti-AIDS drugs. The project covering the Hepatitis C Virus is called "Discovering Dengue Drugs – Together." ([[Dengue]] virus and HCV belong to the same familly, together with [[West Nile virus|West Nile]] and [[Yellow fever]] viruses [http://www.utmb.edu/discoveringdenguedrugs%2Dtogether/]). The software and information about the project can be found at the World Community Grid web site.[http://www.worldcommunitygrid.org]
Current research is focused in virus' [[Protease inhibitor (pharmacology)|protease inhibitors]], with drugs such as [[VX 950|Telaprevir]]. Barriers to the study of HCV include that fact that HCV has a very narrow host range. Hence the only animal model viable for HCV study is the [[chimpanzee]]. The use of [[Replicon (genetics)|replicons]] has been very successful as well but has only been recently discovered. Finally, HCV, as with most all [[RNA]] viruses, exists as a [[viral quasispecies]], making it very difficult to isolate a single strain or receptor type for study.<ref>Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M. "The way forward in HCV treatment - finding the right path." Nat Rev Drug Discov. 2007 Dec;6(12):991-1000.</ref>
==References==
<references/>
== External links ==
* [http://www.liverfoundation.org American Liver Foundation: Comprehensive information about Hepatitis C, including links to chapters for finding local resources]
* [http://www.hivandhepatitis.com/hep_c/hepc_news_genotype.html Academic articles about the HCV six genotypes]
* [http://www.hepatitis-c.org Hepatitis C Virus (HCV) Details]
[[Category:Flaviviruses]]
[[Category:Microbiology]]
[[de:Hepatitis-C-Virus]]
[[fr:Virus de l'hépatite C]]
[[ja:C型肝炎ウイルス]]
[[no:Hepatitt C-virus]]
[[pl:Wirus zapalenia wątroby typu C]]