Herpes simplex virus

Herpes Simplex Virus

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Herpes simplex virus

Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two species of the herpes virus 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....
, which cause infections in human

Human

A human being, also human or man, is a member of a species of bipedalism primates in the family Hominidae . Mitochondrial DNA evidence indicates that modern humans originated in east Africa about 200,000 years ago....
s. Eight members of herpes virus infect human

Human

Chickenpox

Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It generally begins with a vesicular skin rash appearing in two or three waves, mainly on the body and head rather than the hands and becoming itchy raw pockmarks, small open sores which heal mostly without scarring....
or varicella, shingles or herpes zoster (VZV), cytomegalovirus

Cytomegalovirus

Cytomegalovirus is a Virus genus of the Herpesviridae group: in humans it is commonly known as HCMV or Human Herpesvirus 5 . CMV belongs to the Betaherpesvirinae subfamily of Herpesviridae, which also includes Roseolovirus....
(CMV), and various cancer

Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
s, and can cause brain inflammation

Inflammation

Inflammation is the complex biological response of Blood vessel tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue....
(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

Neurotropic virus

A neurotropic virus is a virus which is capable of infecting nerve cells, or which does so preferentially.Related terms include neuroinvasive , and neurovirulent ....
; they enter and hide in the human nervous system

Nervous system

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Encyclopedia

Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two species of the herpes virus family, Herpesviridae

Herpesviridae

Human

Chickenpox

Cytomegalovirus

Cancer

Inflammation

Neurotropic virus

Nervous system

The nervous system is a Neural network of specialized cells that communicate information about an animal's surroundings and itself. It processes this information and causes reactions in other parts of the body....
, 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

Sex organ

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 the reproductive system in a complex organism; in mammals, these include:...
herpes.

An infection

Infection

An infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host resources to multiply ....
by a herpes simplex virus is marked by 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....
s in the skin

Skin

The skin is the outer covering of the body, also known as the epidermis. It is the largest organ of the integumentary system made up of multiple layers of epithelial biological tissue, and guards the underlying muscles, bones, ligaments and organ s....
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 , wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop hemorrhage and begin repair of the damaged vessel....
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

Cell (biology)

The cell is the structural and functional unit of all known Life organisms. It is the smallest unit of an organism that is classified as living, and is often called the building bricks of life....
bodies of nerve

Nerve

A nerve is an enclosed, cable-like bundle of Peripheral nervous system axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons....
s in the area. Some infected people experience sporadic episodes of viral reactivation, followed by transportation of the virus via the nerve's axon

Axon

An axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts action potentialaway from the neuron's cell body or soma....
to the skin, where virus replication and shedding occurs.

Herpes is contagious

Infectious disease

An infectious disease is a clinically evident disease resulting from the presence of pathogenic microbial agents, including pathogenic viruses, pathogenic bacteria, Mycosis, protozoa, multicellular parasites, and aberrant proteins known as prions....
if the carrier 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 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.

Transmission

HSV is transmitted during close contact with an infected person who is shedding virus from the skin, in saliva

Saliva

Saliva is the watery and usually frothy substance produced in the mouths of humans and most other animals. Saliva is produced in and secreted from the salivary glands....
or in secretion

Secretion

Secretion is the process of, elaborating and releasing Chemical compound from a cell , or a secreted chemical substance or amount of substance. In contrast to excretion, the substance may have a certain function, rather than being a waste product....
s from the genitals. This horizontal transmission

Horizontal transmission

Horizontal transmission is the transmission of a bacterial, fungal, or viral infection between members of the same species that are not in a parent-child relationship....
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. In addition, vertical transmission

Vertical transmission

Vertical transmission, also known as Mother-to-child transmission refers to transmission of an infection, such as HIV, hepatitis B, or hepatitis C, from mother to child during the perinatal period, the period immediately before and after birth....
of HSV may occur between mother and child during childbirth, which can be fatal to the infant. The immature immune system

Immune system

An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
of the child is unable to defend against the virus and even if treated, the infection can result in inflammation of the brain (encephalitis

Encephalitis

Not to be confused with syphilis, although that can cause encephalitis as well.Encephalitis is an Acute inflammation of the brain.Encephalitis with meningitis is known as meningoencephalitis....
) 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

Aseptic meningitis

Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining of the brain, or meninges, become inflammation and a pyogenic bacterial source is not to blame....
.

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

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
genome

Genome

In classical genetics, the genome of a diploid organism including eukarya refers to a full set of chromosomes or genes in a gamete; thereby, a regular somatic cell contains two full sets of genomes....
encased within an icosahedral

Icosahedron

In geometry, an icosahedron isany polyhedron having 20 faces, but usually a regular icosahedron is implied, which has equilateral triangle s as faces....
protein cage called the capsid

Capsid

Lipid bilayer

A lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cell ....
called the envelope. The envelope is joined to the capsid by means of a tegument

Viral tegument

Certain viruses contain a tegument, which is a cluster of non-essential and essential proteins that line the space between the cell membrane and nucleocapsid of many enveloped viruses....
. 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 HSV-1 and HSV-2 are complex, and contain two unique regions called the long unique region (U_L) and the short unique region (U_S). Of the 74 known ORFs, U_L contains 56 viral genes, whereas U_S 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....
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 biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
s involved in DNA replication

DNA replication

DNA replication, the basis for heredity, is a fundamental process occurring in all living organisms to copy their DNA. This process is "semiconservative replication" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand....
and the production of certain envelope

Viral envelope

Many viruses have viral envelopes covering their protein capsids. The envelopes are typically derived from portions of the host cell membranes , but include some viral glycoproteins....
glycoprotein

Glycoprotein

Not to be confused with peptidoglycan or proteoglycan.Glycoproteins are proteins that contain oligosaccharide chains covalently attached to their Peptide side-chains....
s. Expression of late genes occurs last; this group of genes predominantly encode proteins that form the virion particle.

Five proteins from (U_L) 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....
, UL18, UL35, UL38 and the major capsid protein UL19.

The open reading frames (ORFs) of HSV-1
Gene	Protein	Function/description	Gene	Protein	Function/description
UL1	Glycoprotein Glycoprotein Not to be confused with peptidoglycan or proteoglycan.Glycoproteins are proteins that contain oligosaccharide chains covalently attached to their Peptide side-chains.... L	Surface and membrane	UL38	UL38; VP19C	Capsid assembly and DNA maturation
UL2	UL2	Uracil-DNA glycosylase Uracil-DNA glycosylase Uracil-DNA glycosylase, also known as UNG, is a human gene though orthologs exist ubiquitously among prokaryotes and eukaryotes and even in some DNA viruses....	UL39	UL39	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.... (Large subunit)
UL3	UL3	unknown	UL40	UL40	Ribonucleotide reductase (Small subunit)
UL4	UL4	unknown	UL41	UL41; VHS	Tegument protein; Virion host shutoff
UL5	UL5	DNA replication DNA replication DNA replication, the basis for heredity, is a fundamental process occurring in all living organisms to copy their DNA. This process is "semiconservative replication" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand....	UL42	UL42	DNA polymerase DNA polymerase A DNA polymerase is an enzyme that catalyze the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their 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 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....	UL6	Processing and packaging DNA	UL43	UL43	Membrane protein
UL7	UL7	Virion maturation	UL44	Glycoprotein C	Surface and membrane
UL8	UL8	DNA helicase/primase complex-associated protein	UL45	UL45	Membrane protein; C-type lectin
UL9	UL9	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	Tegument proteins
UL10	Glycoprotein M	Surface and membrane	UL47	UL47; VP13/14	Tegument protein
UL11	UL11	virion exit and secondary envelopment	UL48	VP16 (Alpha-TIF)	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'TAATGARAT^3'.
UL12	UL12	Alkaline exonuclease Exonuclease Exonucleases are enzymes that cleave nucleotides one at a time from an end of a polynucleotide chain. These enzymes hydrolyze phosphodiester bonds from either the 3' or 5' terminus of a polynucleotide molecule....	UL49	UL49A	Envelope protein
UL13	UL13	Serine Serine Serine is an organic compound with the chemical formula hydrogenoxygen2carbonCHCH2OH.... -threonine Threonine Threonine is an a-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as Chemical polarity.... 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 catalysis, cellular location, or association with other proteins....	UL50	UL50	dUTP diphosphatase DUTP diphosphatase In enzymology, a dUTP diphosphatase is an enzyme that catalysis the chemical reactionThus, the two substrate of this enzyme are dUTP and water, whereas its two product are dUMP and diphosphate....
UL14	UL14	Tegument Viral tegument Certain viruses contain a tegument, which is a cluster of non-essential and essential proteins that line the space between the cell membrane and nucleocapsid of many enveloped viruses.... protein	UL51	UL51	Tegument protein
UL15	Terminase	Processing and packaging of DNA	UL52	UL52	DNA helicase/primase complex protein
UL16	UL16	Tegument protein	UL53	Glycoprotein K	Surface and membrane
UL17	UL17	Processing and packaging DNA	UL54	IE63; ICP27	Transcriptional regulation
UL18	VP23	Capsid Capsid A capsid is the protein shell of a virus . It consists of several oligomeric structural subunits made of protein, called protomers; at the same time the 3-dimensional morphological subunits that can be observed, which may or may not correspond to individual proteins, are called capsomeres.... protein	UL55	UL55	Unknown
UL19	VP5	Major capsid protein	UL56	UL56	Unknown
UL20	UL20	Membrane protein	US1	ICP22; IE68	Viral replication
UL21	UL21	Tegument protein	US2	US2	Unknown
UL22	Glycoprotein H	Surface and membrane	US3 US3 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 founder of Blue Note Records....	US3	Serine/threonine-protein kinase
UL23	Thymidine kinase Thymidine kinase Thymidine kinase TK, is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, . It can be found in most living cell s....	Peripheral to DNA replication	US4	Glycoprotein G	Surface and membrane
UL24	UL24	unknown	US5 US5 US5 is a multinational boy band pop music band, first established in 2005. The group's launch to fame was financed by Lou Pearlman, an Orlando confidence trickster who made millions with a penny stock "pump and dump" scheme and a fraudulent savings program....	Glycoprotein J	Surface and membrane
UL25	UL25	Processing and packaging DNA	US6	Glycoprotein D	Surface and membrane
UL26	P40; VP24; VP22A	Capsid protein	US7	Glycoprotein I	Surface and membrane
UL27	Glycoprotein B	Surface and membrane	US8	Glycoprotein E	Surface and membrane
UL28	ICP18.5	Processing and packaging DNA	US9	US9	Tegument protein
UL29	UL29	Major DNA-binding protein	US10	US10	Capsid/Tegument protein
UL30	DNA polymerase DNA polymerase A DNA polymerase is an enzyme that catalyze the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best-known for their role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....	DNA replication	US11	US11; Vmw21	Binds DNA and RNA
UL31	UL31	Nuclear matrix protein	US12	ICP47; IE12	Inhibits MHC class I MHC class I There are two primary classes of major histocompatibility complex molecules, class I and MHC class II. MHC class I molecules are found on almost 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. It delivers cytosolic peptides into the endoplasmic reticulum , where they bind to nascent MHC class I molecules....
UL32	UL32	Envelope Viral envelope Many viruses have viral envelopes covering their protein capsids. The envelopes are typically derived from portions of the host cell membranes , but include some viral glycoproteins.... glycoprotein Glycoprotein Not to be confused with peptidoglycan or proteoglycan.Glycoproteins are proteins that contain oligosaccharide chains covalently attached to their Peptide side-chains....	RS1	ICP4; IE175	Activates gene transcription
UL33	UL33	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 Herpesviridaees. 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 gene or a phase of viral gene expression....	ICP0; IE110; a0	E3 ubiquitin Ubiquitin Ubiquitin is a highly-conserved regulatory protein that is :wiktionary:ubiquitous expressed in eukaryotes. Ubiquitination refers to the post-translational modification of a protein by the covalent attachment of one or more ubiquitin monomers.... ligase that activates viral gene transcription and counteracts the interferon Interferon Interferons are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, parasites and tumor cells.... response
UL34	UL34	Inner nuclear membrane protein	LRP1	LRP1	Latency-related protein
UL35	VP26	Capsid protein	LRP2	LRP2	Latency-related protein
UL36	UL36	Large tegument protein	RL1	RL1; ICP34.5	Neurovirulence factor. Antagonizes PKR Protein kinase R Protein kinase R is a protein protecting against viral infections. EIF2AK2 is its human gene.... by de-phosphorylating eIF4a.
UL37	UL37	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, Herpesviridae infections. The LAT RNA is produced by transcription from a certain region of the viral DNA....	none	Latency-associated transcript

Cellular entry

Entry of HSV into the host cell involves interactions of several glycoprotein

Glycoprotein

Transmembrane receptor

Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cell's plasma membrane, but also in the biological membrane of some subcellular compartments and organelles....
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....
. 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 a receptor called the herpesvirus entry mediator receptor (HVEM

TNFRSF14

Tumor necrosis factor receptor superfamily, member 14 , also known as TNFRSF14, is a human gene.ReferencesFurther reading...
) 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. Glycoprotein B interacts with glycosaminoglycan

Glycosaminoglycan

Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit....
s on the surface of the host cell.

Genetic inoculation

After the viral capsid enters the cellular cytoplasm

Cytoplasm

The cytoplasm is the part of a Cell that is enclosed within the plasma membrane. In eukaryote cells the cytoplasm contains organelles, such as mitochondrion, that are filled with liquid kept separate from the rest of the cytoplasm by biological membranes....
, it is transported to the cell nucleus

Cell nucleus

In cell biology, the nucleus , also sometimes referred to as the "control center", is a membrane-enclosed organelle found in all eukaryote cell ....
. 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 super secondary structural motif found in proteins that creates adhesion forces in parallel alpha helices....
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 which describes the corners or intersections of geometric shapes. Vertices are commonly used in computer graphics to define the corners of surfaces in 3d models, where each such point is given as a vector....
. The DNA exits the capsid in a single linear segment.

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, examining, and sorting microscopic particles suspended in a stream of fluid. It allows simultaneous Parametric model analysis of the physical and/or chemical characteristics of single cells flowing through an optical and/or electronic detection apparatus....
s on another member of the herpes virus family, KSHV

Kaposi's sarcoma-associated herpesvirus

Kaposi's sarcoma-associated herpesvirus is the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8....
, indicates the possibility of an additional lytic stage

Lytic cycle

The lytic cycle is one of the two cycles of virus reproduction, the other being the lysogenic cycle. These cycles should not, however, be seen as separate, but rather as somewhat interchangeable....
, 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 a-TIF protein joins the viral particle and aids in immediate-early

Early protein

Transcription (genetics)

Transcription is the synthesis of RNA under the direction of DNA. RNA synthesis, or transcription, is the process of transcribing DNA nucleotide sequence information into RNA sequence information....
. 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 ribonucleic acid is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcription from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes....
, helps in viral replication, and regulates gene expression

Gene expression

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 as protein or 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

Capsid

A capsid is the protein shell of a virus . It consists of several oligomeric structural subunits made of protein, called protomers; at the same time the 3-dimensional morphological subunits that can be observed, which may or may not correspond to individual proteins, are called capsomeres....
- 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 small bubble of liquid within a cell. More technically, a vesicle is a small, intracellular, membrane-enclosed sac that stores or transports substances within a cell....
.

Latent infection

HSV 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.Cells found in a ganglion are called ganglion cells, though this term is also sometimes used to refer specifically to Retinal ganglion cells....
. During latent infection of a cell, HSV express Latency Associated Transcript (LAT) RNA

RNA

Ribonucleic acid is a type of molecule that consists of a long chain of nucleotide units. Each nucleotide consists of a nucleobase, a ribose sugar, and a phosphate....
. 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 neuron

Neuron

Neurons are responsive cell in the nervous system that process and transmit information by electrochemical Signal . They are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves....
s may bind to herpes virus DNA and regulate latency

Virus latency

Virus latency is the ability of a pathogenic virus to lie dormancy 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 an important transactivator

Transactivation

Transactivation is an increased rate of gene expression triggered either by biological processes or by artificial means....
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 deacytalization

Histone

In biology, histones are the chief protein components of chromatin. They act as spools around which DNA winds, and they 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 Herpesviridaees. 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 gene or a phase of viral gene expression....
dissociates NRSF from the ICP4 gene and thus prevents silencing of the viral DNA.

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

Alzheimer's disease

Scientists discovered a link between HSV-1 and Alzheimer’s disease in 1979. In the presence of a certain gene variation (APOE

Apolipoprotein E

Apolipoprotein E is an apolipoprotein found in the chylomicron and intermediate density lipoproteins that binds to a specific Receptor on hepatocytes and peripheral cells....
-epsilon4 allele carriers), 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 type 1 does not appear to cause any neurological damage and thus increase the risk of Alzheimer’s.

A 2008 study published in The Journal of Pathology, has shown a striking localization of herpes simplex virus type 1 DNA within the beta-amyloid plaques that characterize Alzheimer's disease, and suggests that this virus is a major cause of the plaques and hence probably a significant aetiological factor in Alzheimer's disease.

External links

BBC News
BBC News

BBC News, formerly BBC News and Current Affairs, is the department within the BBC responsible for the corporation's news-gathering and production of news programmes on BBC television, radio and online....