Home      Discussion      Topics      Dictionary      Almanac
Signup       Login
Herpes simplex virus

Herpes simplex virus

Discussion
Ask a question about 'Herpes simplex virus'
Start a new discussion about 'Herpes simplex virus'
Answer questions from other users
Full Discussion Forum
 
Encyclopedia
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known as Human herpes virus 1 and 2 (HHV-1 and -2), are two members of the herpes virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

 family, Herpesviridae
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...

, that infect human
Human
Humans are the only living species in the Homo genus...

s. Both HSV-1 (which produces most cold sores) and HSV-2 (which produces most genital herpes) are ubiquitous and contagious
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...

. They can be spread when an infected person is producing and shedding
Viral shedding
Viral shedding refers to the successful reproduction, expulsion, and host-cell infection caused by virus progeny. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods.The term is used...

 the virus.

Symptoms of herpes simplex virus infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

 include watery blister
Blister
A blister is a small pocket of fluid within the upper layers of the skin, typically caused by forceful rubbing , burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid called serum or plasma...

s in the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

 or mucous membranes of the mouth, lips or genitals. Lesions heal with a scab
Coagulation
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, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...

 characteristic of herpetic disease. Sometimes, the viruses cause very mild or atypical symptoms during outbreaks. However, as neurotropic and neuroinvasive viruses
Neurotropic virus
A neurotropic virus is a virus which is capable of infecting nerve cells, or which does so preferentially. Such viruses thereby largely evade the usual immune response—which acts only within the blood system.- Terminology :...

, HSV-1 and -2 persist in the body by becoming latent and hiding from the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 in the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 bodies of nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...

s. After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the nerve's axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

 to the skin, where virus replication and shedding occur and cause new sores.

Transmission


HSV-1 and -2 are transmitted from contact with an infectious area of the skin during reactivations of the virus. Although less likely, the herpes viruses can be transmitted during latency. Transmission is likely to occur during symptomatic reactivation of the virus that causes visible and typical skin sores. Asymptomatic reactivation means that the virus causes atypical, subtle or hard to notice symptoms that are not identified as an active herpes infection. Atypical symptoms are often attributed to other causes such as a yeast infection. HSV-1 is usually acquired orally during childhood, but may also be sexually transmitted. HSV-2 is primarily a sexually transmitted infection but rates of HSV-1 genital infections are increasing.

Both viruses may also be transmitted vertically during childbirth, although the real risk is very low. The risk of infection is minimal if the mother has no symptoms or exposed blisters during delivery. The risk is considerable when the mother gets the virus for the first time during late pregnancy.

Symptoms resulting from primary infection with HSV are usually much more severe than subsequent outbreaks, as the body has not had a chance to produce antibodies. This first outbreak of oral herpes (cold sores) carries a low (≈1%) risk of developing aseptic meningitis
Aseptic meningitis
Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings...

.

Viral structure


Animal herpes viruses all share some common properties. The structure of herpes viruses consists of a relatively large double-stranded, linear DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 encased within an icosahedral
Icosahedron
In geometry, an icosahedron is a regular polyhedron with 20 identical equilateral triangular faces, 30 edges and 12 vertices. It is one of the five Platonic solids....

 protein cage called the capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...

, which is wrapped in a lipid bilayer
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...

 called the envelope. The envelope is joined to the capsid by means of a tegument
Viral tegument
A viral tegument or tegument, more commonly known as a viral matrix, is a cluster of proteins that lines the space between the envelope and nucleocapsid of all herpesviruses. The tegument generally contains proteins that aid in viral DNA replication and evasion of the immune response, typically...

. This complete particle is known as the virion. HSV-1 and HSV-2 each contain at least 74 genes (or open-reading frames, ORFs) within their genomes, although speculation over gene crowding allows as many as 84 unique protein coding genes by 94 putative ORFs. 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 HSV1 and HSV2 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. Transcription of HSV genes is catalyzed by RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...

 of the infected host. Immediate early gene
Immediate early gene
Immediate early genes are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli. They represent a standing response mechanism that is activated at the transcription level in the first round of response to stimuli, before any new proteins are synthesized...

s, which encode proteins that regulate the expression of early and late viral genes, are the first to be expressed following infection. Early gene
Early protein
The classification of viral proteins as early proteins or late proteins depends on their relationship with genome replication. While many viruses are described as expressing early and late proteins, this definition of these terms is commonly reserved for class I DNA viruses...

 expression follows, to allow the synthesis of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s involved in DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

 and the production of certain envelope
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...

 glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

s. Expression of late genes occurs last; this group of genes predominantly encode proteins that form the virion particle.

Five proteins from (UL) form the viral capsid; UL6
HHV capsid portal protein
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 . The protein is commonly referred to as the HSV-1 UL-6 protein because it is the transcription product of Herpes gene UL-6.The Herpes viral DNA enters and exits...

, UL18, UL35, UL38 and the major capsid protein UL19.

Cellular entry



Entry of HSV into the host cell involves interactions of several glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

s on the surface of the enveloped virus, with receptors on the surface of the host cell. 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
Viral entry
Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variation among viruses, the generalities are quite similar...

. 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.
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
Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...

. A second glycoprotein, glycoprotein D (gD), binds specifically to at least one of three known entry receptors. These include herpesvirus entry mediator(HVEM
TNFRSF14
Tumor necrosis factor receptor superfamily member 14 is a protein that in humans is encoded by the TNFRSF14 gene. It is also known as "herpesvirus entry mediator" .-Interactions:...

), nectin
Nectin
Nectins and Nectin-like molecules are families of cellular adhesion molecules involved in Ca2+-independent cellular adhesion.Nectins are ubiquitously expressed and have adhesive roles in a wide range of tissues such as the adherens junction of epithelia or the chemical synapse of the neuronal...

-1 and 3-O sulfated heparan sulfate. The receptor 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. Glycoprotein B interacts with glycosaminoglycan
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...

s on the surface of the host cell.

Genetic inoculation


After the viral capsid enters the cellular cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

, it is transported to the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

. 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
Leucine zipper
A leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression...

 sequence of amino acids which allow them to adhere to each other. Each icosahedral capsid contains a single portal, located in one vertex
Vertex (geometry)
In geometry, a vertex is a special kind of point that describes the corners or intersections of geometric shapes.-Of an angle:...

.
The DNA exits the capsid in a single linear segment.

Immune evasion


HSV evades the immune system through interference with MHC class I presentation of antigen on the cell surface. It achieves this through blockade of the TAP transporter induced by the secretion of ICP-47 by HSV. TAP maintains the integrity of the MHC class I
MHC class I
MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...

 molecule before it is transported via the golgi apparatus for recognition by CD8+ CTLs
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...

 on the cell surface. ICP-47 disrupts this integrity, preventing the capture of cytosolic proteins for CTL recognition and thus evades CTL destruction.

Replication



Following infection of a cell, herpes virus proteins, called immediate-early, early
Early protein
The classification of viral proteins as early proteins or late proteins depends on their relationship with genome replication. While many viruses are described as expressing early and late proteins, this definition of these terms is commonly reserved for class I DNA viruses...

, and late, are produced. Research using flow cytometry
Flow cytometry
Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...

 on another member of the herpes virus family, Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...

, indicates the possibility of an additional lytic stage
Lytic cycle
The lytic cycle is one of the two cycles of viral reproduction, the other being the lysogenic cycle. The lytic cycle is typically considered the main method of viral replication, since it results in the destruction of the infected cell...

, delayed-late. These stages of lytic infection, particularly late lytic, are distinct from the latency stage. 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
Early protein
The classification of viral proteins as early proteins or late proteins depends on their relationship with genome replication. While many viruses are described as expressing early and late proteins, this definition of these terms is commonly reserved for class I DNA viruses...

 transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

. The virion host shutoff protein (VHS or UL41) is very important to viral replication. This enzyme shuts off protein synthesis in the host, degrades host mRNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

, helps in viral replication, and regulates gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 of viral proteins. The viral genome immediately travels to the nucleus but the VHS protein remains in the cytoplasm.

The late proteins are used in to form the capsid and the receptors on the surface of the virus. Packaging of the viral particles — including the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

, core and the capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...

 - 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
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

.

Latent infection


HSVs may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia
Ganglion
In anatomy, a ganglion is a biological tissue mass, most commonly a mass of nerve cell bodies. Cells found in a ganglion are called ganglion cells, though this term is also sometimes used to refer specifically to retinal ganglion cells....

. HSV-1 tends to reside in the trigeminal ganglia
Trigeminal ganglion
The trigeminal ganglion is a sensory ganglion of the trigeminal nerve that occupies a cavity in the dura mater, covering the trigeminal impression near the apex of the petrous part of the temporal bone.-Relations:It is somewhat crescentic in shape, with its convexity...

, while HSV-2 tends to reside in the sacral ganglia
Sacral ganglia
The sacral ganglia are paravertebral ganglia of the sympathetic trunk. As the sympathetic trunk heads inferiorly down the sacrum, it turns medially. There are generally four or five sacral ganglia...

, but note that these are tendencies only, not fixed behavior. During such latent infection of a cell, HSVs express Latency Associated Transcript (LAT) RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

. 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 subsequent, usually symptomatic, periodic recurrences or "outbreaks" characteristic of non-latency. Whether or not recurrences are noticeable (symptomatic) or not, viral shedding occurs to produce further infections (usually in a new host, if any). A protein found in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s may bind to herpes virus DNA and regulate latency
Virus latency
Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection...

. Herpes virus DNA contains a gene for a protein called ICP4, which is an important transactivator
Transactivation
In molecular biology and genetics, transactivation is an increased rate of gene expression triggered either by biological processes or by artificial means.- Natural transactivation :...

 of genes associated with lytic infection in HSV-1. 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 deacetylation
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...

 occurs atop the ICP4 gene sequence to prevent initiation of transcription from this gene, thereby preventing transcription of other viral genes involved in the lytic cycle. Another HSV protein reverses the inhibition of ICP4 protein synthesis. ICP0
HHV Infected Cell Polypeptide 0 (ICP0)
Human Herpes Virus Infected Cell Polypeptide 0 is a protein, encoded by the DNA of herpes viruses. It is produced by herpes viruses during the earliest stage of infection, when the virus has recently entered the host cell; this stage is known as the immediate-early or α phase of viral gene...

 dissociates NRSF from the ICP4 gene and thus prevents silencing of the viral DNA.

The virus can be reactivated by illnesses such as colds and influenza, eczema, emotional and physical stress, gastric upset, fatigue or injury, by menstruation and possibly exposure to bright sunlight.

Viral genome

The open reading frames (ORFs) of HSV-1
Gene Protein Function/description Gene Protein Function/description
UL1  Glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

 L http://www.uniprot.org/uniprot/P10185
Surface and membrane UL38  UL38; VP19C http://www.uniprot.org/uniprot/P32888 Capsid assembly and DNA maturation
UL2  UL2 http://www.uniprot.org/uniprot/P10186 Uracil-DNA glycosylase
Uracil-DNA glycosylase
Uracil-DNA glycosylase, also known as UNG or UDG, is a human gene though orthologs exist ubiquitously among prokaryotes and eukaryotes and even in some DNA viruses. The first uracil DNA-glycosylase was isolated from Escherichia coli....

UL39  UL39 http://www.uniprot.org/uniprot/P08543 Ribonucleotide reductase
Ribonucleotide reductase
Ribonucleotide reductase is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA. The reaction catalyzed by RNR is strictly conserved in all living organisms...

 (Large subunit)
UL3  UL3 http://www.uniprot.org/uniprot/P10187 unknown UL40  UL40 http://www.uniprot.org/uniprot/P06474 Ribonucleotide reductase (Small subunit)
UL4  UL4 http://www.uniprot.org/uniprot/P10188 unknown UL41  UL41; VHS http://www.uniprot.org/uniprot/P10225 Tegument protein; Virion host shutoff
UL5  UL5 http://www.expasy.org/uniprot/Q2MGV2 DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

UL42  UL42 http://www.expasy.org/uniprot/Q4H1G9 DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....

 processivity factor
UL6 Portal protein UL-6
HHV capsid portal protein
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 . The protein is commonly referred to as the HSV-1 UL-6 protein because it is the transcription product of Herpes gene UL-6.The Herpes viral DNA enters and exits...

 
Twelve of these proteins constitute the capsid portal ring through which DNA enters and exits the capsid. UL43  UL43 http://www.expasy.org/uniprot/P10227 Membrane protein
UL7  UL7 http://www.expasy.org/uniprot/P10190 Virion maturation UL44  Glycoprotein C http://www.expasy.org/uniprot/P10228 Surface and membrane
UL8  UL8 http://www.expasy.org/uniprot/P10192 DNA helicase/primase complex-associated protein UL45  UL45 http://www.expasy.org/uniprot/P10229 Membrane protein; C-type lectin
UL9  UL9 http://www.expasy.org/uniprot/P10193 Replication origin
Origin of replication
The origin of replication is a particular sequence in a genome at which replication is initiated. This can either be DNA replication in living organisms such as prokaryotes and eukaryotes, or RNA replication in RNA viruses, such as double-stranded RNA viruses...

-binding protein
UL46  VP11/12 http://www.expasy.org/uniprot/P08314 Tegument proteins
UL10  Glycoprotein M http://www.expasy.org/uniprot/P04288 Surface and membrane UL47  UL47; VP13/14 http://www.expasy.org/uniprot/P10231 Tegument protein
UL11  UL11 http://www.expasy.org/uniprot/P04289 virion exit and secondary envelopment UL48  VP16 (Alpha-TIF) http://www.expasy.org/uniprot/P04486 Virion maturation; activate IEGs
Immediate early gene
Immediate early genes are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli. They represent a standing response mechanism that is activated at the transcription level in the first round of response to stimuli, before any new proteins are synthesized...

 by interacting with the cellular transcription factors Oct-1 and HCF. Binds to the sequence 5'TAATGARAT3'.
UL12  UL12 http://www.expasy.org/uniprot/Q68978 Alkaline exonuclease
Exonuclease
Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3’ or the 5’ end occurs. Its close relative is the endonuclease, which cleaves phosphodiester bonds in the middle ...

UL49  UL49A http://www.expasy.org/uniprot/O09800 Envelope protein
UL13  UL13 http://www.expasy.org/uniprot/Q9QNF2 Serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

-threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...

 protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...

UL50  UL50 http://www.expasy.org/uniprot/P10234 dUTP diphosphatase
DUTP diphosphatase
In enzymology, a dUTP diphosphatase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are dUTP and H2O, whereas its two products are dUMP and diphosphate....

UL14  UL14 http://www.expasy.org/uniprot/P04291 Tegument
Viral tegument
A viral tegument or tegument, more commonly known as a viral matrix, is a cluster of proteins that lines the space between the envelope and nucleocapsid of all herpesviruses. The tegument generally contains proteins that aid in viral DNA replication and evasion of the immune response, typically...

 protein
UL51  UL51 http://www.expasy.org/uniprot/P10234 Tegument protein
UL15  Terminase http://www.expasy.org/uniprot/P04295 Processing and packaging of DNA UL52  UL52 http://www.expasy.org/uniprot/P10236 DNA helicase/primase complex protein
UL16  UL16 http://www.expasy.org/uniprot/P10200 Tegument protein UL53  Glycoprotein K http://www.expasy.org/uniprot/P68333 Surface and membrane
UL17  UL17 http://www.expasy.org/uniprot/P10201 Processing and packaging DNA UL54  IE63; ICP27 http://www.expasy.org/uniprot/P10238 Transcriptional regulation
UL18  VP23 http://www.expasy.org/uniprot/P10202 Capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...

 protein
UL55  UL55 http://www.expasy.org/uniprot/P10239 Unknown
UL19  VP5 http://www.expasy.org/uniprot/P06491 Major capsid protein UL56  UL56 http://www.expasy.org/uniprot/P10240 Unknown
UL20  UL20 http://www.expasy.org/uniprot/P10204 Membrane protein US1  ICP22; IE68 http://www.expasy.org/uniprot/P04485 Viral replication
UL21  UL21 http://www.expasy.org/uniprot/P10205 Tegument protein US2  US2 http://www.expasy.org/uniprot/P06485 Unknown
UL22  Glycoprotein H http://www.expasy.org/uniprot/P06477 Surface and membrane US3  US3 http://www.expasy.org/uniprot/P04413 Serine/threonine-protein kinase
UL23  Thymidine kinase
Thymidine kinase
Thymidine kinase is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, . It can be found in most living cells. It is present in two forms in mammalian cells, TK1 and TK2...

 http://www.expasy.org/uniprot/O55259
Peripheral to DNA replication US4  Glycoprotein G http://www.expasy.org/uniprot/P06484 Surface and membrane
UL24  UL24 http://www.expasy.org/uniprot/P10208 unknown US5  Glycoprotein J http://www.expasy.org/uniprot/P06480 Surface and membrane
UL25  UL25 http://www.expasy.org/uniprot/P10209 Processing and packaging DNA US6  Glycoprotein D http://www.expasy.org/uniprot/A1Z0Q5 Surface and membrane
UL26  P40; VP24; VP22A http://www.expasy.org/uniprot/P10210 Capsid protein US7  Glycoprotein I http://www.expasy.org/uniprot/P06487 Surface and membrane
UL27  Glycoprotein B
Herpesvirus Glycoprotein B
Herpesvirus glycoprotein B is a viral glycoprotein that is involved in the viral cell entry of Herpes simplex virus . Herpesviruses have an envelope and an outer lipid bilayer which contains twelve surface glycoproteins...

 http://www.expasy.org/uniprot/A1Z0P5
Surface and membrane US8  Glycoprotein E http://www.expasy.org/uniprot/Q703F0 Surface and membrane
UL28  ICP18.5 http://www.expasy.org/uniprot/P10212 Processing and packaging DNA US9  US9 http://www.expasy.org/uniprot/P06481 Tegument protein
UL29  UL29; ICP8 http://www.expasy.org/uniprot/Q2MGU6 Major DNA-binding protein US10  US10 http://www.expasy.org/uniprot/P06486 Capsid/Tegument protein
UL30  DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....

 http://www.expasy.org/uniprot/Q4ACM2
DNA replication US11  US11; Vmw21 http://www.expasy.org/uniprot/P56958 Binds DNA and RNA
UL31  UL31 http://www.expasy.org/uniprot/Q25BX0 Nuclear matrix protein US12  ICP47; IE12 http://www.expasy.org/uniprot/P03170 Inhibits MHC class I
MHC class I
MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...

 pathway by preventing binding of antigen to TAP
Transporter associated with antigen processing
Transporter associated with antigen processing is a member of the ATP-binding-cassette transporter family. It delivers cytosolic peptides into the endoplasmic reticulum , where they bind to nascent MHC class I molecules....

UL32  UL32 http://www.expasy.org/uniprot/P10216 Envelope
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...

 glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

RS1 ICP4; IE175 http://www.expasy.org/uniprot/P08392 Major transcriptional activator. Essential for progression beyond the immediate-early phase of infection. IEG
Immediate early gene
Immediate early genes are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli. They represent a standing response mechanism that is activated at the transcription level in the first round of response to stimuli, before any new proteins are synthesized...

 transcription repressor.
UL33  UL33 http://www.expasy.org/uniprot/P10217 Processing and packaging DNA ICP0
HHV Infected Cell Polypeptide 0 (ICP0)
Human Herpes Virus Infected Cell Polypeptide 0 is a protein, encoded by the DNA of herpes viruses. It is produced by herpes viruses during the earliest stage of infection, when the virus has recently entered the host cell; this stage is known as the immediate-early or α phase of viral gene...

 
ICP0; IE110; α0 http://www.expasy.org/uniprot/P08393 E3 ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

 ligase that activates viral gene transcription and counteracts the interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

 response
UL34  UL34 http://www.expasy.org/uniprot/P10218 Inner nuclear membrane protein LRP1  LRP1 http://www.expasy.org/uniprot/P17588 Latency-related protein
UL35  VP26 http://www.expasy.org/uniprot/P10219 Capsid protein LRP2  LRP2 http://www.expasy.org/uniprot/P17589 Latency-related protein
UL36  UL36 http://www.expasy.org/uniprot/P10220 Large tegument protein RL1  RL1; ICP34.5 http://www.expasy.org/uniprot/O12396 Neurovirulence factor. Antagonizes PKR
Protein kinase R
Protein kinase RNA-activated also known as protein kinase R , interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 is an enzyme that in humans is encoded by the EIF2AK2 gene.PKR protects against viral...

 by de-phosphorylating eIF4a.
UL37  UL37 http://www.expasy.org/uniprot/P10216 Capsid assembly LAT
HHV Latency Associated Transcript
HHV Latency Associated Transcript is a length of RNA which accumulates in cells hosting long-term, or latent, Human Herpes Virus infections. The LAT RNA is produced by genetic transcription from a certain region of the viral DNA...

 
none http://www.expasy.org/uniprot/Q69079 Latency-associated transcript

Treatment and vaccine development

For more details on treatment of herpes simplex virus, see Herpes simplex.
For more information on vaccines, see Herpes simplex vaccine


Herpes viruses establish lifelong infections and the virus cannot currently be eradicated from the body. Treatment usually involves general-purpose antiviral drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

s that interfere with viral replication, reducing the physical severity of outbreak-associated lesions and lowering the chance of transmission to others. Studies of vulnerable patient populations have indicated that daily use of antivirals such as acyclovir and valacyclovir can reduce reactivation rates.

In vitro research has indicated that Aloe Vera
Aloe vera
Aloe vera, pronounced , also known as the true aloe or medicinal aloe, is a species of succulent plant in the genus Aloe that is believed to have originated in the Sudan. Aloe vera grows in arid climates and is widely distributed in Africa, India, Nepal and other arid areas.The species is...

 may be effective against genital herpes.

Connection between facial sores and Alzheimer's disease


In the presence of a certain gene variation (APOE
Apolipoprotein E
Apolipoprotein E is a class of apolipoprotein found in the chylomicron and IDLs that binds to a specific receptor on liver cells and peripheral cells. It is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.-Function:...

-epsilon4 allele carriers), a possible link between HSV-1 (i.e., the virus that causes cold sores or oral herpes) and Alzheimer’s disease was reported in 1979. HSV-1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimer's disease. This research identifies HSVs as the pathogen most clearly linked to the establishment of Alzheimer’s. Without the presence of the gene allele, HSV-1 does not appear to cause any neurological damage or increase the risk of Alzheimer’s.
Many more Alzheimer's disease susceptibility genes, including the major players APOE, clusterin, complement receptor 1 and PICALM are involved in the herpes simplex life cycle as curated in this database

External links