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Herpes simplex virus
TEM micrograph of a herpes simplex virus.
TEM micrograph of a herpes simplex virus. A micrograph, microphotograph or photomicrograph is a Photograph or similar image taken through a Microscope or similar device to show
Virus classification
Group: Group I (dsDNA)
Family: Herpesviridae
Subfamily: Alphaherpesvirinae
Genus: Simplexvirus
Species

Herpes simplex virus 1 (HWJ-1)
Herpes simplex virus 2 (HWJ-2)
This article is about the virus. Virus classification involves naming and placing Viruses into a taxonomic system A DNA virus is a Virus that has DNA as its Genetic material and replicates using a DNA-dependent DNA polymerase. The Herpesviridae are a large family of DNA viruses that cause diseases in animals including humans Alphaherpesvirinae is a subfamily of Herpesviridae primarily distinguished by reproducing more quickly than other subfamilies of Herpesviridae Herpes simplex is a Viral disease caused by Herpes simplex viruses both herpes simplex virus 1 (HSV-1 and herpes simplex virus 2 (HSV-2 cause herpes simplex For information about the disease, see Herpes simplex. Herpes simplex is a Viral disease caused by Herpes simplex viruses both herpes simplex virus 1 (HSV-1 and herpes simplex virus 2 (HSV-2 cause herpes simplex

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. The Herpesviridae are a large family of DNA viruses that cause diseases in animals including humans Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus [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). Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus Herpes simplex is a Viral disease caused by Herpes simplex viruses both herpes simplex virus 1 (HSV-1 and herpes simplex virus 2 (HSV-2 cause herpes simplex Chickenpox is a highly contagious illness caused by primary infection with Varicella zoster virus (VZV Herpes zoster (or simply zoster) commonly known as shingles, is a Viral disease characterized by a painful skin rash with Blisters in a limited Cytomegalovirus (CMV (from the Greek cyto-, "cell" and -megalo-, "large" is a viral Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens 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. A neurotropic virus is a Virus which is capable of infecting Nerve cells, or which does so preferentially The nervous system is a Network of specialized cells that communicate information about an animal's surroundings and itself 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 oral ulcer (from Latin ulcus) is the name for the appearance of an open sore inside the mouth caused by a break in the Mucous membrane or the epithelium A sex organ, or primary sexual characteristic, as narrowly defined is any of the anatomical parts of the body which are involved in sexual reproduction and constitute

An infection by a herpes simplex virus is marked by watery blisters in the skin or mucous membranes of the mouth, lips or genitals. An infection is the detrimental Colonization of a host Organism by a foreign Species. A blister is a small pocket of fluid within the upper layers of the skin The skin is the outer covering of living tissue of an animal (or plant The mucous membranes (or mucosae; singular mucosa) are linings of mostly endodermal origin covered in Epithelium, which are involved in [1] Lesions heal with a scab characteristic of herpetic disease. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby 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. The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called A nerve is an enclosed cable-like bundle of peripheral Axons (the long slender projections of Neurons. 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. An axon or nerve fiber is a long slender projectionof a nerve cell or Neuron, that conducts electrical impulses away from the neuron's Cell [2]

Herpes is contagious if the carrier is producing and shedding the virus. An infectious disease is a clinically evident Disease resulting from the presence of Pathogenic microbial agents including Pathogenic viruses Pathogenic Chronic since 1992 ( talk) 2200 12 December 2007 (UTC --> Viral shedding 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.

Contents

Transmission

Main article: Herpes simplex

HSV is transmitted during close contact with an infected person who is shedding virus from the skin, in saliva or in secretions from the genitals. Herpes simplex is a Viral disease caused by Herpes simplex viruses both herpes simplex virus 1 (HSV-1 and herpes simplex virus 2 (HSV-2 cause herpes simplex For the band see Saliva (band; for the village in Azerbaijan see Səliva. Secretion is the process of segregating elaborating and releasing chemicals from a cell, or a secreted Chemical substance or amount of substance 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. Horizontal transmission is the transmission of a Bacterial, Fungal, or Viral Infection between members of the same species that are not in a [3] In addition, vertical transmission of HSV may occur between mother and child during childbirth, which can be fatal to the infant. Vertical transmission, also known as Mother-to-child transmission refers to transmission of an Infection, such as HIV, Hepatitis B, or Hepatitis [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. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Encephalitis is an acute Inflammation of the Brain, commonly caused by a viral Infection. 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 vagina (from Latin, literally " Sheath " or " Scabbard " is a fibromuscular tubular tract leading from the Uterus 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. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Aseptic meningitis, or sterile meningitis is a condition in which the layers lining of the brain or Meninges, become inflamed and a Pyogenic Bacterial [1]

Microbiology

Viral structure

Animal 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. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby In Geometry, an icosahedron ( Greek: eikosaedron, from eikosi twenty + hedron seat /ˌaɪ For the leaf bug see Miridae. A capsid is the protein shell of a virus. A lipid bilayer or bilayer lipid membrane ( BLM) is a membrane composed of Lipid molecules (usually Phospholipids. Many Viruses (eg influenza and many animal viruses have viral envelopes covering their protein Capsids The envelopes are typically derived from portions of The envelope is joined to the capsid by means of a tegument. Certain viruses contain a tegument, which is a cluster of non-essential and essential proteins that line the space between the envelope and Nucleocapsid of many enveloped This complete particle is known as the virion. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable [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. RNA polymerase II (also called RNAP II and Pol II) is an enzyme found in eukaryotic cells [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. Immediate early genes ( IEGs) are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli Early gene expression follows, to allow the synthesis of enzymes involved in DNA replication and the production of certain envelope glycoproteins. The classification of viral Proteins as early proteins or Late proteins depends on their relationship with Genome replication Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules Many Viruses (eg influenza and many animal viruses have viral envelopes covering their protein Capsids The envelopes are typically derived from portions of Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached 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. HHV Capsid Portal Protein, or HSV-1 UL-6 protein, is the Protein which forms a cylindrical portal in the Capsid of Herpes simplex virus [5]

The open reading frames (ORFs) of HSV-1[8][6]
Gene Protein Function/description Gene Protein Function/description
UL1 Glycoprotein L [2] Surface and membrane UL38 UL38; VP19C [3] Capsid assembly and DNA maturation
UL2 UL2 [4] Uracil-DNA glycosylase UL39 UL39 [5] Ribonucleotide reductase (Large subunit)
UL3 UL3 [6] unknown UL40 UL40 [7] Ribonucleotide reductase (Small subunit)
UL4 UL4 [8] unknown UL41 UL41; VHS [9] Tegument protein; Virion host shutoff[9]
UL5 UL5 [10] DNA replication UL42 UL42 [11] DNA polymerase processivity factor
UL6 UL6 [12] Processing and packaging DNA UL43 UL43 [13] Membrane protein
UL7 UL7 [14] Virion maturation UL44 Glycoprotein C [15] Surface and membrane
UL8 UL8 [16] DNA helicase/primase complex-associated protein UL45 UL45 [17] Membrane protein; C-type lectin[10]
UL9 UL9 [18] Replication origin-binding protein UL46 VP11/12 [19] Tegument proteins
UL10 Glycoprotein M [20] Surface and membrane UL47 UL47; VP13/14 [21] Tegument protein
UL11 UL11 [22] virion exit and secondary envelopment UL48 VP16 (Alpha-TIF) [23] Virion maturation; activate IEGs by interacting with the cellular transcription factors Oct-1 and HCF. Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached Uracil-DNA glycosylase, also known as UNG, is a human Gene. Ribonucleotide reductase (RNR is an Enzyme that controls the cellular concentration of Deoxyribonucleotides Biosynthesis begins with the building up of DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules A DNA Polymerase is an Enzyme that assists in DNA replication. HHV Capsid Portal Protein, or HSV-1 UL-6 protein, is the Protein which forms a cylindrical portal in the Capsid of Herpes simplex virus Helicases are a class of Enzymes vital to all living Organisms They are motor proteins that move directionally along a Nucleic acid phosphodiester backbone DNA primase is an Enzyme involved in the replication of DNA by creating an RNA primer The Origin of replication (also called the replication origin) is a particular sequence in a Genome at which replication is initiated Immediate early genes ( IEGs) are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli Binds to the sequence 5'TAATGARAT3'.
UL12 UL12 [24] Alkaline exonuclease UL49 UL49A [25] Envelope protein
UL13 UL13 [26] Serine-threonine protein kinase UL50 UL50 [27] dUTP diphosphatase
UL14 UL14 [28] Tegument protein UL51 UL51 [29] Tegument protein
UL15 Terminase [30] Processing and packaging of DNA UL52 UL52 [31] DNA helicase/primase complex protein
UL16 UL16 [32] Tegument protein UL53 Glycoprotein K [33] Surface and membrane
UL17 UL17 [34] Processing and packaging DNA UL54 IE63; ICP27 [35] Transcriptional regulation
UL18 VP23 [36] Capsid protein UL55 UL55 [37] Unknown
UL19 VP5 [38] Major capsid protein UL56 UL56 [39] Unknown
UL20 UL20 [40] Membrane protein US1 ICP22; IE68 [41] Viral replication
UL21 UL21 [42] Tegument protein[11] US2 US2 [43] Unknown
UL22 Glycoprotein H [44] Surface and membrane US3 US3 [45] Serine/threonine-protein kinase
UL23 Thymidine kinase [46] Peripheral to DNA replication US4 Glycoprotein G [47] Surface and membrane
UL24 UL24 [48] unknown US5 Glycoprotein J [49] Surface and membrane
UL25 UL25 [50] Processing and packaging DNA US6 Glycoprotein D [51] Surface and membrane
UL26 P40; VP24; VP22A [52] Capsid protein US7 Glycoprotein I [53] Surface and membrane
UL27 Glycoprotein B [54] Surface and membrane US8 Glycoprotein E [55] Surface and membrane
UL28 ICP18. In Chemistry, an alkali (from Arabic: Al-Qaly القلي القالي) is a basic, ionic salt of an Alkali metal Exonucleases are enzymes (found as individual enzymes or as parts of larger enzyme complexes that cleave Nucleotides one at a time from an end of a polynucleotide chain Serine (abbreviated as Ser or S) is an Organic compound with the formula H[[oxygen O]]2 CCH NH sub>2CH2OH Threonine (abbreviated as Thr or T) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH(OHCH3 A protein kinase is a Kinase Enzyme that modifies other Proteins by chemically adding Phosphate groups to them ( Phosphorylation) In Enzymology, a dUTP diphosphatase ( is an Enzyme that catalyzes the Chemical reaction dUTP + H2O \rightleftharpoons Certain viruses contain a tegument, which is a cluster of non-essential and essential proteins that line the space between the envelope and Nucleocapsid of many enveloped For the leaf bug see Miridae. A capsid is the protein shell of a virus. Us3 is a Jazz-rap group founded in London in 1991. Their name was inspired by a Horace Parlan recording produced by Alfred Lion, the Thymidine kinase TK is an Enzyme, a Phosphotransferase (a Kinase) 2'-deoxythymidine kinase ATP-thymidine 5'-phosphotransferase. US5 is a multinational all-male pop band first established in 2005 The Studebaker US6 is a class of Trucks manufactured by Studebaker during World War II, produced in the United States from 1941-1945 and in the Soviet 5 [56] Processing and packaging DNA US9 US9 [57] Tegument protein
UL29 UL29 [58] Major DNA-binding protein US10 US10 [59] Capsid/Tegument protein
UL30 DNA polymerase [60] DNA replication US11 US11; Vmw21 [61] Binds DNA and RNA
UL31 UL31 [62] Nuclear matrix protein US12 ICP47; IE12 [63] Inhibits MHC class I pathway by preventing binding of antigen to TAP
UL32 UL32 [64] Envelope glycoprotein RS1 ICP4; IE175 [65] Activates gene transcription
UL33 UL33 [66] Processing and packaging DNA ICP0 ICP0; IE110; α0 [67] E3 ubiquitin ligase that activates viral gene transcription and counteracts the interferon response
UL34 UL34 [68] Inner nuclear membrane protein LRP1 LRP1 [69] Latency-related protein
UL35 VP26 [70] Capsid protein LRP2 LRP2 [71] Latency-related protein
UL36 UL36 [72] Large tegument protein RL1 RL1; ICP34. A DNA Polymerase is an Enzyme that assists in DNA replication. There are two primary classes of Major histocompatibility complex (MHC molecules class I and MHC class II. Transporter associated with antigen processing ( TAP) is a member of the ATP-binding-cassette transporter family. Many Viruses (eg influenza and many animal viruses have viral envelopes covering their protein Capsids The envelopes are typically derived from portions of Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached Retinoschisis (X-linked juvenile 1, also known as RS1, is a human Gene. Human Herpes Virus (HHV Infected Cell Polypeptide 0 (ICP0 is a Protein, encoded by the DNA of herpes viruses It is produced by herpes viruses during the Ubiquitin is a highly-conserved regulatory Protein that is ''ubiquitously'' expressed in Eukaryotes. Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents 5 [73] Neurovirulence factor. Antagonizes PKR by de-phosphorylating eIF4a. Protein kinase R (Eukaryotic translation initiation factor 2-alpha kinase 2 is a protein protecting against Viral infections EIF2AK2 is its human Gene
UL37 UL37 [74] Capsid assembly LAT none [75] Latency-associated transcript

Cellular entry

A simplified diagram of HSV replication
A simplified diagram of HSV replication

Entry of HSV into the host cell involves interactions of several glycoproteins on the surface of the enveloped virus, with receptors on the surface of the host cell. HHV Latency Associated Transcript ( HHV LAT) is a length of RNA which accumulates in cells hosting long-term or latent, Human Herpes Virus (HHV Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached Transmembrane receptors are Integral membrane proteins which reside and operate typically within a cell's Plasma membrane, but also in the membranes of The envelope covering the virus particle, when bound to specific receptors on the cell surface, will fuse with the host cell membrane and create an opening, or pore, through which the virus enters the host cell.

The sequential stages of HSV entry are analogous to those of other viruses. Chronic since 1992 ( talk) 2200 12 December 2007 (UTC --> Viral entry 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. Heparan sulfate (HS is a linear Polysaccharide found in all animal tissues 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. Tumor necrosis factor receptor superfamily member 14 (herpesvirus entry mediator, also known as TNFRSF14, is a human Gene. 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. Glycosaminoglycans (GAGs or mucopolysaccharides are long unbranched Polysaccharides consisting of a repeating Disaccharide unit

Genetic inoculation

After the viral capsid enters the cellular cytoplasm, it is transported to the cell nucleus. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed 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. A leucine zipper, aka leucine scissors, is a super secondary Structural motif found in Proteins that creates adhesion forces in parallel In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this [13] Each icosahedral capsid contains a single portal, located in one vertex. In Geometry, an icosahedron ( Greek: eikosaedron, from eikosi twenty + hedron seat /ˌaɪ In Geometry, a vertex (plural "vertices" is a special kind of point. [14][15] The DNA exits the capsid in a single linear segment. [16]

Replication

Consequent to a cell being infected, groups of Herpes virus proteins, termed immediate-early, early, and late proteins, are produced following specific time periods. The classification of viral Proteins as early proteins or Late proteins depends on their relationship with Genome replication 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. Flow cytometry is a technique for counting examining and sorting microscopic particles suspended in a stream of fluid Kaposi's sarcoma-associated herpesvirus ( KSHV) is the eighth human Herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is lytic cycle is one of the two cycles of viral Reproduction, the other being the Lysogenic cycle. [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 α-TIF protein joins the viral particle and aids in immediate-early transcription. The classification of viral Proteins as early proteins or Late proteins depends on their relationship with Genome replication Transcription is the synthesis of RNA under the direction of DNA 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. Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such 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. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby For the leaf bug see Miridae. A capsid is the protein shell of a virus. Here, concatemers of the viral genome are separated by cleavage and are placed into pre-formed capsids. A concatemer is a long continuous DNA molecule that contains multiple copies of the same DNA sequences linked in series 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. A vesicle is a small bubble of liquid within a cell A more formal definition in Cell biology, would be that a vesicle is a relatively small intracellular membrane-enclosed [20]

Latent infection

HSV may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia. In Anatomy, a ganglion (pl ganglia) is a tissue mass. Neurology In neurological contexts ganglia are composed mainly of [1] During latent infection of a cell, HSV express Latency Associated Transcript (LAT) RNA. HHV Latency Associated Transcript ( HHV LAT) is a length of RNA which accumulates in cells hosting long-term or latent, Human Herpes Virus (HHV Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units 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. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Chronic since 1992 ( talk) 2200 12 December 2007 (UTC --> Virus 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. Transactivation is an increased rate of gene expression triggered either by endogenous cellular or viral proteins - transactivators. [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). RE1-silencing transcription factor, also known as REST, is a human Gene. 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. In Biology, histones are the chief Protein components of Chromatin. [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. Human Herpes Virus (HHV Infected Cell Polypeptide 0 (ICP0 is a Protein, encoded by the DNA of herpes viruses It is produced by herpes viruses during the [24]

Reactivation

The 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 medication

Nucleoside analogs

Oral Prodrug
 Drug Analog of Nucleoside Nucleoside Family
Famciclovir[25]
(bioavailability: 75% oral)
(trade names: Famvir)		 Penciclovir
(1. See also Adenosine triphosphate (ATP Famciclovir ( INN) (fæmˈsaɪkloʊvɪr is a Guanine analogue Antiviral drug used for the treatment of various Herpesvirus infections most commonly Penciclovir ( INN) (pɛnˈsaɪklovir is a Guanine analogue Antiviral drug used for the treatment of various Herpesvirus infections 5% oral, IV, locally topical)
(Denavir, Fenistil)		 \Bigg\}guanosine purine
Valaciclovir
(55% oral)
(Valtrex)		 Aciclovir
(10-20% oral)
(Zovirax, Zovir)
Valganciclovir
(60% oral)
(Valcyte)		 Ganciclovir
(5% oral, IV, locally intraocular)
(Cytovene, Cymevene)
Brivudine[26] (BVDU)   thymidine pyrimidine

Treatment is available in the form of antiviral medications such as nucleoside analogs, which reduce the duration of symptoms of a herpex simplex virus outbreak and accelerate healing. Guanosine is a Nucleoside comprising Guanine attached to a Ribose ( Ribofuranose) ring via a β-N9- Glycosidic bond. Purine ( 1) is a heterocyclic Aromatic Organic compound, consisting of a Pyrimidine ring fused to an Imidazole ring Valaciclovir ( INN) or valacyclovir ( USAN) is an Antiviral drug used in the management of Herpes simplex and Herpes zoster Aciclovir ( INN Valganciclovir hydrochloride ( Valcyte, manufactured by Roche is an Antiviral Medication used to treat Cytomegalovirus Infections Ganciclovir ( INN) (gænˈsaɪkləvɪr is an Antiviral medication used to treat or prevent Cytomegalovirus (CMV infections Brivudine is an Antiviral drug used in the treatment of Herpes zoster. Thymidine (more precisely called deoxythymidine; can also be labelled deoxyribosylthymine, and thymine deoxyriboside) is a Chemical compound Pyrimidine is a Heterocyclic Aromatic Organic compound similar to Benzene and Pyridine, containing two Nitrogen Atoms Nucleoside analogues are a range of antiviral products used to prevent Viral replication in infected cells Nucleoside analogs are molecules which possess a similarity to natural nucleotides - the building-blocks of DNA and RNA. See also Adenosine triphosphate (ATP Nucleotides are Organic compounds that consist of three joined structures a nitrogenous base a Sugar, and a Phosphate group Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units 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. Chronic since 1992 ( talk) 2200 12 December 2007 (UTC --> Viral replication In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism 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. In Medicine, a subclinical infection refers to an inapparent asymptomatic Infection, or an infection that has such a mild course that it does not alert the Patient Chronic since 1992 ( talk) 2200 12 December 2007 (UTC --> Viral shedding

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. Cytotoxicity is the quality of being toxic to cells Examples of toxic agents are a Chemical substance, an Immune cell or some types of Venom [27]

Fusion inhibitors

Fusion inhibitors prevent "fusion" of the viral envelope with the cell membrane. This prevents viral entry to the cell. Chronic since 1992 ( talk) 2200 12 December 2007 (UTC --> Viral entry One example of a fusion inhibitor is Docosanol, which is supplied in a cream formulation for topical application. Docosanol, also known as behenyl alcohol, is a saturated Fatty alcohol used mainly as an antiviral agent, specifically for treatment of " [28]

Helicase-primase inhibitors

One of three key protein structures involved in HSV DNA replication is the Helicase-Primase structure. Helicases are a class of Enzymes vital to all living Organisms They are motor proteins that move directionally along a Nucleic acid phosphodiester backbone DNA primase is an Enzyme involved in the replication of DNA by creating an RNA primer 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 supplements

The amino acid lysine has demonstrated the ability to reduce the duration of infection through inhibiting the replication of the HSV. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Lysine (abbreviated as Lys or K) is an α- Amino acid with the Chemical formula HO2CCH(NH2(CH24NH2 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. Arginine (abbreviated as Arg or R) is an α- Amino acid. The L-form is one of the 20 most common natural amino acids [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 medication

Undecylenic 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). Undecylenic / Undecenoic Acid is an organic unsaturated Fatty acid derived from natural Castor oil. 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. Butylated hydroxytoluene (BHT also known as Butylhydroxytoluene, is a Lipophilic (fat-soluble Organic compound that is primarily used as an [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. A ribozyme (from ribo nucleic acid en' zyme', also called RNA Enzyme or catalytic RNA is an RNA Molecule that catalyzes 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 resistance

Resistance 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. Helicases are a class of Enzymes vital to all living Organisms They are motor proteins that move directionally along a Nucleic acid phosphodiester backbone DNA primase is an Enzyme involved in the replication of DNA by creating an RNA primer 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 research

Main article: Herpes simplex

Herpevac, a vaccine for HSV-2 is currently (as of February 2007) undergoing clinical testing in women in the United States and Canada. Herpes simplex is a Viral disease caused by Herpes simplex viruses both herpes simplex virus 1 (HSV-1 and herpes simplex virus 2 (HSV-2 cause herpes simplex [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]

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