Encyclopedia
| Herpes simplex virus
Encyclopedia
|
| Tutorials | Encyclopedia | Dictionary | Directory |
|
Herpes simplex virus
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two species of the herpes virus family, Herpesviridae, which cause infections in humans.[1] Eight members of herpesviridae infect humans to cause a variety of illnesses including cold sores, chickenpox or varicella, shingles or herpes zoster (VZV), cytomegalovirus (CMV), and various cancers, and can cause brain inflammation (encephalitis). All viruses in the herpes family produce life-long infections. They are also called Human Herpes Virus 1 and 2 (HHV-1 and HHV-2) and are neurotropic and neuroinvasive viruses; they enter and hide in the human nervous system, accounting for their durability in the human body. HSV-1 is commonly associated with herpes outbreaks of the face known as cold sores or fever blisters, whereas HSV-2 is more often associated with genital herpes. An infection by a herpes simplex virus is marked by watery blisters in the skin or mucous membranes of the mouth, lips or genitals.[1] Lesions heal with a scab characteristic of herpetic disease. However, the infection is persistent and symptoms may recur periodically as outbreaks of sores near the site of original infection. After the initial, or primary, infection, HSV becomes latent in the cell bodies of nerves in the area. Some infected people experience sporadic episodes of viral reactivation, followed by transportation of the virus via the nerve's axon to the skin, where virus replication and shedding occurs.[2] Herpes is contagious if the carrier is producing and shedding the virus. This is especially likely during an outbreak but possible at other times. There is no cure yet, but there are treatments which reduce the likelihood of viral shedding.
TransmissionHSV is transmitted during close contact with an infected person who is shedding virus from the skin, in saliva or in secretions from the genitals. This horizontal transmission of the virus is more likely to occur when sores are present, although viral shedding, and therefore transmission, does occur in the absence of visible sores.[3] In addition, vertical transmission of HSV may occur between mother and child during childbirth, which can be fatal to the infant.[4] The immature immune system of the child is unable to defend against the virus and even if treated, the infection can result in inflammation of the brain (encephalitis) that may cause brain damage. Transmission occurs when the infant passes through the birth canal, but the risk of infection is reduced if there are no symptoms or exposed blisters during delivery. The first outbreak after exposure to HSV is commonly more severe than future outbreaks, as the body has not had a chance to produce antibodies; this first outbreak carries a low (~1%) risk of developing aseptic meningitis.[1] MicrobiologyViral structureAnimal herpes viruses all share some common properties. The structure of herpes viruses consists of a relatively large double-stranded, linear DNA genome encased within an icosahedral protein cage called the capsid, which is wrapped in a lipid bilayer called the envelope. The envelope is joined to the capsid by means of a tegument. This complete particle is known as the virion.[5] HSV-1 and HSV-2 each contain at least 74 genes (or open-reading frames, ORFs) within their genomes,[6] although speculation over gene crowding allows as many as 84 unique protein coding genes by 94 putative ORFs.[7] These genes encode a variety of proteins involved in forming the capsid, tegument and envelope of the virus, as well as controlling the replication and infectivity of the virus. These genes and their functions are summarized in the table below. The genomes of HSV-1 and HSV-2 are complex, and contain two unique regions called the long unique region (UL) and the short unique region (US). Of the 74 known ORFs, UL contains 56 viral genes, whereas US contains only 12.[6] Transcription of HSV genes is catalyzed by RNA polymerase II of the infected host.[6] Immediate early genes, which encode proteins that regulate the expression of early and late viral genes, are the first to be expressed following infection. Early gene expression follows, to allow the synthesis of enzymes involved in DNA replication and the production of certain envelope glycoproteins. Expression of late genes occurs last; this group of genes predominantly encode proteins that form the virion particle.[6] Five proteins from (UL) form the viral capsid; UL6, UL18, UL35, UL38 and the major capsid protein UL19.[5] Cellular entry
A simplified diagram of HSV replication The sequential stages of HSV entry are analogous to those of other viruses. At first, complementary receptors on the virus and the cell surface bring the viral and cell membranes into proximity. In an intermediate state, the two membranes begin to merge, forming a hemifusion state. Finally, a stable entry pore is formed through which the viral envelope contents are introduced to the host cell.[12] In the case of a herpes virus, initial interactions occur when a viral envelope glycoprotein called glycoprotein C (gC) binds to a cell surface particle called heparan sulfate. A second glycoprotein, glycoprotein D (gD), binds specifically to a receptor called the herpesvirus entry mediator receptor (HVEM) and provides a strong, fixed attachment to the host cell. These interactions bring the membrane surfaces into mutual proximity and allow for other glycoproteins embedded in the viral envelope to interact with other cell surface molecules. Once bound to the HVEM, gD changes its conformation and interacts with viral glycoproteins H (gH) and L (gL), which form a complex. The interaction of these membrane proteins results in the hemifusion state. Afterward, gB interaction with the gH/gL complex creates an entry pore for the viral capsid.[12] Glycoprotein B interacts with glycosaminoglycans on the surface of the host cell. Genetic inoculationAfter the viral capsid enters the cellular cytoplasm, it is transported to the cell nucleus. Once attached to the nucleus at a nuclear entry pore, the capsid ejects its DNA contents via the capsid portal. The capsid portal is formed by twelve copies of portal protein, UL6, arranged as a ring; the proteins contain a leucine zipper sequence of amino acids which allow them to adhere to each other.[13] Each icosahedral capsid contains a single portal, located in one vertex.[14][15] The DNA exits the capsid in a single linear segment.[16] ReplicationConsequent to a cell being infected, groups of Herpes virus proteins, termed immediate-early, early, and late proteins, are produced following specific time periods. Research using a new flow cytometry methodology in another member of the herpes virus family, KSHV, indicates the possibility of an additional lytic stage, delayed-late.[17] These stages of lytic infection, particularly late lytic, are distinct from the latency stage. For example, in the case of HSV-1, no protein products are detected during latency whereas, they are detected during the lytic cycle. The early proteins transcribed are used in the regulation of genetic replication of the virus. On entering the cell, an ?-TIF protein joins the viral particle and aids in immediate-early transcription. The virion host shutoff protein (VHS or UL41) is very important to viral replication.[9] This enzyme shuts off protein synthesis in the host, degrades host mRNA, helps in viral replication, and regulates gene expression of viral proteins. The viral genome immediately travels to the nucleus but the VHS protein remains in the cytoplasm.[18][19] The late proteins are used in forming the capsid and the receptors on the surface of the virus. Packaging of the viral particles - including the genome, core and the capsid - occurs in the nucleus of the cell. Here, concatemers of the viral genome are separated by cleavage and are placed into pre-formed capsids. HSV-1 undergoes a process of primary and secondary envelopment. The primary envelope is acquired by budding into the inner nuclear membrane of the cell. This then fuses with the outer nuclear membrane releasing a naked capsid into the cytoplasm. The virus acquires its final envelope by budding into cytoplasmic vesicles.[20] Latent infectionHSV may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia.[1] During latent infection of a cell, HSV express Latency Associated Transcript (LAT) RNA. LAT is known to regulate the host cell genome and interferes with natural cell death mechanisms. By maintaining the host cells, LAT expression preserves a reservoir of the virus, which allows later recurrences to produce further infections. A protein found in neurons may bind to herpes virus DNA and regulate latency. Herpes virus DNA contains a gene for a protein called ICP4, which an important transactivator of genes associated with lytic infection in HSV-1.[21] Elements surrounding the gene for ICP4 bind a protein known as the human neuronal protein Neuronal Restrictive Silencing Factor (NRSF) or human Repressor Element Silencing Transcription Factor (REST). When bound to the viral DNA elements, histone deacytalization occurs atop the ICP4 gene sequence to prevent initiation of transription from this gene, thereby preventing transcription of other viral genes involved in the lytic cycle.[22][23] Another HSV protein reverses the inhibition of ICP4 protein synthesis. ICP0 dissociates NRSF from the ICP4 gene and thus prevents silencing of the viral DNA.[24] ReactivationThe virus can be reactivated due to the effects of other illnesses such as cold and influenza, eczema, emotional and physical stress, exposure to bright sunlight, gastric upset, fatigue or injury, as well as menstruation resulting in the reappearance of surface sores. Anti-viral medicationNucleoside analogs
Treatment is available in the form of antiviral medications such as nucleoside analogs, which reduce the duration of symptoms of a herpes simplex virus outbreak and accelerate healing. Nucleoside analogs are molecules which possess a similarity to natural nucleotides - the building-blocks of DNA and RNA. Active herpes simplex virus will replicate; a virus replicating in the presence of these analogs will incorporate them into its DNA, so that its genetic material will contain defects and mutations. As a result, the next generation of virus will be damaged and reduced in number. Nucleoside analogs are typically used at the first symptoms of an viral outbreak to reduce the duration of the outbreak and improve healing of the lesion. Treatment taken prior to the appearance of lesions may avert or reduce the symptoms of the outbreak. Occasionally nucleoside analogs are used as a daily suppressive therapy, and taken daily for several years. Suppressive therapy reduces frequency of symptoms and recurrence of outbreaks. In addition, suppressive therapy reduces subclinical viral shedding, lowering the risk of transmission through sexual contact or kissing. Common nucleoside analogs are listed in the table above. Of these, Ganciclovir is known to have cytotoxic effects on infected cells but Acyclovir is not known to have this effect.[27] Fusion inhibitorsFusion inhibitors prevent "fusion" of the viral envelope with the cell membrane. This prevents viral entry to the cell. One example of a fusion inhibitor is Docosanol, and other fat-alcohol (C6-C22) which are supplied since 1994 in lip-gloss and (later) in a cream formulation for topical application.[28] Helicase-primase inhibitorsOne of three key protein structures involved in HSV DNA replication is the Helicase-Primase structure. New research compounds which bind to this megamolecule show remarkable effectiveness against HSV. In particular, BAY 57-1293 has shown positive results in animal models of HSV infection.[29] Dietary supplementsThe amino acid lysine has demonstrated the ability to reduce the duration of infection through inhibiting the replication of the HSV. When foods high in lysine (such as lentils) are consumed in preference to foods high in arginine, HSV replication may be inhibited; conversely, consuming foods high in arginine (such as nuts or peanuts) may interfere with the therapeutic use of lysine.[30] However, according to the American Social Health Association: "While some studies have suggested that lysine supplements can reduce the frequency of recurrences or healing time, other trials have been unable to replicate those results. Therefore, there is not sufficient information to discern how effective it may be, in addition to what the effective dosages or frequency of L-lysine may be."[25] Other anti-viral medicationUndecylenic acid (Castor oil derivative) is proven to have anti-bacterial and anti-viral properties that are effective on viral skin infections such as the herpes simplex virus (HSV). Used as a cream formulation, this treatment reduces viral shedding and severity of itching associated with an HSV outbreak, but does not prevent episodes, speed up healing, or reduce lesion size.[31] Butylated hydroxytoluene (BHT), commonly available as a food preservative, has been shown in vitro to inactivate enveloped viruses including herpes.[32][33] In-vivo studies of topical application to animals confirmed the anti-viral activity of BHT during outbreaks.[34] BHT has not been clinically tested and approved to treat herpes in humans. Researchers at the University of Florida have made a hammerhead ribozyme that targets and cleaves the mRNA of essential genes in HSV-1. The hammerhead which targets the mRNA of the UL20 gene greatly reduced the level of HSV-1 ocular infection in rabbits and reduced the viral yield in vivo.[35] Drug resistanceResistance of HSVes in cell culture has been reported for nucleosides in the range of 10-2 to 10-4 and for Helicase-Primase inhibitors in the range of 10-4 to 10-6. However, in the clinic roughly 1-2% of the patients are infected by nucleoside-resistant HSVes. In the immunocompromised patient population such as transplant, AIDS or cancer patients the resistance rate can reach up to 10%. Vaccine researchHerpevac, a vaccine for HSV-2 is currently (as of February 2007) undergoing clinical testing in women in the United States and Canada.[36][37] Previous studies have determined that this vaccine is approximately 70% effective in women, but does not prevent the disease in men.[38] Currently the University of Florida is seeking a company interested in commercializing a novel method for preventing the spread and recurrence of herpes simplex virus. Researchers at the University of Florida have developed a gene therapy that employs hammerhead ribozymes to inhibit herpes viral replication. When administered by a single injection after the initial infection, the therapy provides life-long inhibition of recurring outbreaks.[39] ReferencesExternal links
de:Herpes-simplex-Virus dv:???????? ??????? hr:Herpes simpleks id:Virus herpes simpleks it:Herpes simplex lt:Herpesas nl:Herpes simplexvirus ja:?????????? no:Herpes simplex pl:Wirus opryszczki pospolitej ro:Virusul herpes simplex simple:Herpes simplex sl:Virus herpesa simpleksa fi:Herpes simplex sv:Herpes simplex ta:?????????? ???????? tr:Herpes simpleks zh:?????? Source: Wikipedia | The above article is available under the GNU FDL. | Edit this article
|
|
top
©2008-2009 TutorGig.com. All Rights Reserved. Privacy Statement
