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Viruses Genomes - HUMAN HERPESVIRUS
Human herpesvirus
causes a range of human disorders including cold sores, roseola, Epstein Barr Virus ( EBV) and genital warts
The
name herpes comes from the Greek
herpein
which means to creep, a reference to a characteristic pattern of
skin eruptions. These viruses cause chronic/latent/recurrent infections.
Epidemiology of the common Herpesvirus infections puzzled clinicians
for many years. In 1950, Burnet and Buddingh showed that HSV (Herpes
simplex virus or HHV-1 - see below) could become latent after a
primary infection, becoming reactivated after later provocation.
The
Herpesvirus family is divided into three sub-families
Alphaherpesvirinae which are neurotropic and have a rapid
replication cycle and (usually) a broad host and cell range
,
Betaherpesvirinae and
Gammaherpesvirinae which differ
in genome size and structure but which both replicate more slowly
and in a much more restricted range of cells of glandular and/or
lymphatic origin. The same host can be
infected with multiple distinct and unique types. Approximately
100 Herpesviruses have been isolated, at least one for most animal
species. To date, there are eight known human Herpesviruses:
Ictalurivirus,
Mardivirus, Simplexvirus, Varicellovirus, Iltovirus, Cytomegalovirus,
Roseolovirus, Muromegalovirus, Lymphocryptovirus and Rhadinovirus.
The structure of the herpesvirus particle is very complex. The core
consists of a toroidal shape with the large DNA genome wound around
a proteinaceous core. The complex capsid surrounds the core. Outside
the capsid is the tegument, a protein-filled region which appears
amorphous in electron micrographs. On the outside of the particle
is the envelope, which contains numerous glycoproteins. All herpesviruses
are almost indistinguishable in electron micrographs.
It is a characteristic of all herpesviruses that, following primary infection,
the virus establishes a latentinfection in the
host and may reactivate at any stage. Reactivation is frequently,
but not always, associated with further disease.
There is no treatment that can cure herpes.
Hierarchy Description:
- Genus: Simplexvirus
- Species:
Human herpesvirus 1
- Strain: 17
Genome accession number: X14112
EMBL reference
- Medline references:
| Journal citation |
Pubmed ID |
| J. Gen. Virol. 69:1531-1574 (1988) |
2839594 |
| J. Gen. Virol. 69:2831-2846 (1988) |
2846760 |
| J. Mol. Biol. 181(1):1-13 (1985) |
2984429 |
| Nucleic Acids Res. 14(4):1727-1745 (1986) |
3005980 |
| J. Gen. Virol. 73:971-973 (1992) |
1321882 |
- Taxonomy:
10298
HHV-1 is also known as herpes simplex type (HSV-1). HSV-1 is a neurotrophic alpha-herpesvirus that only naturally occur in
humans. There are no animal reservoirs. HSV-1 mostly infects oral mucosa but can infect genital mucosa and causes most forms of
non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in
the dorsal root ganglion. The virus does not replicate, but both the host cells and the virus survive. At unpredictable times, the virus
begins multiplying again. It then goes through a period called
shedding. During those times, the virus can be passed into bodily
fluids and infect other people. A third to half of the times shedding occurs without any symptoms at all. It then is periodically
reactivated throughout life causing mostly benign conditions.
Herpes simplex infection is initiated by direct, intimate, contact. HSV-1 usually establishes latency in the trigeminal ganglion,
a collection of nerve cells near the ear. From there, it tends to recur on the lower lip or face in the form of cold sores. The initial
localised infection may be inapparent or produce vesicular lesions. The virus replicates in the cells at the base of the lesion, and the
fluid in the lesion contains infectious virus. The lesion is caused both by cellular cytotoxicity and immunopathology. The lesion will
ulcerate, then crust over. If the initial infection is in a previously uninfected host who is, antibody negative, there may be systemic
manifestations such as fever, lymphadenopathy, and malaise. Latent infection of the neurons produces no damage to the nerve. The virus
can be reactivated by sunlight, fever, stress, or hormonal changes.
HSV-1 infection is usually mild, especially when it affects the lips, face, or genitals. However, in some cases type 1 can recur
spontaneously in the eye, causing ocular herpes, a potentially serious infection which can lead to blindness. In very rare cases HSV-1
can spread spontaneously to the brain, causing herpes encephalitis, a dangerous infection that can lead to death. HSV-1 is also the usual
cause of herpes whitlow, an infection on the finger, and "wrestler's herpes," (herpes gladiatorum) a herpes infection on the chest or face.
It can also cause Primary Herpetic Gingivostomatitis which manifests as either a few intraoral ulcers and no systemic features, to severe
oral ulceration with constitutional upset.
Under a microscope, HSV-1 and 2 are virtually identical, sharing approximately 50% of their DNA. Both types infect the body's
mucosal surfaces, usually the mouth or genitals, and then establish latency in the nervous system. For both types, at least two-thirds
of infected people have no symptoms, or symptoms too mild to notice. However, both types can recur and spread even when no symptoms are present.
Most people have herpes simplex - 70% have facial herpes (cold sores) and 10% have genital herpes in the UK. These figures
are even higher in other countries including the USA and the developing world.
Links:
http://www.herpes.com/HSV-1-2.html
http://www.dentistry.leeds.ac.uk/oralpath/viruses/viral%20infections/HSV.htm
- Genus: Simplexvirus
- Species:
Human herpesvirus 2
- Strain: HG52
Genome accession number: Z86099
EMBL reference
- Medline references:
| Journal citation |
Pubmed ID |
| J. Gen. Virol. 68 (1) 19-38 (1987) |
3027242 |
| J. Gen. Virol. 72 (12) 3057-75 (1991) |
1662697 |
| J. Gen. Virol. 73 ( 8) 2167-71 (1992) |
1322965 |
- Taxonomy:
10298
HHV-2 is also known as herpes simplex type (HSV2) It is a neurotrophic alpha-herpesvirus that only naturally occur in
humans. HSV-2 mostly infects genital mucosa, but can infect oral mucosa. HSV-2 usually sets up residence in the sacral ganglion at
the base of the spine. From there, it recurs in the genital area, this difference is not absolute either HSV-1 or HSV-2 can reside
in either or both parts of the body and infect oral and/or genital areas, see above.
Genital Herpes can infect anyone who has sex, even if only once. An estimated 22% of adults from varying backgrounds,
income levels and ethnic groups have HSV-2. HSV-2 is often so mild that an estimated two thirds of those infected don’t even
realize they have it, it rarely causes complications or spreads to other parts of the body. In the other third however early symptoms
of a genital herpes outbreak include, itching or burning feeling in the genital or anal area, pain in the legs, buttocks, discharge
of fluid from the vagina and a feeling of pressure in the abdomen. Within a few days, sores appear near where the virus has entered
the body, such as on the mouth, penis, or vagina. They also can occur inside the vagina and on the cervix in women, or in the urinary
passage of women and men. Small red bumps appear first, develop into blisters, and then become painful open sores. Over several days,
the sores become crusty and then heal without leaving a scar. Other symptoms that may go with the first episode of genital herpes
are fever, headache, muscle aches, painful or difficult urination and swollen glands in the groin area.
HHV-2 is the most common cause of neonatal herpes, a rare but dangerous infection in newborns.
Genital herpes, like other genital diseases that produce lesions, increase a person's risk of contracting the HIV or
other viruses. Also, prior to better treatments for AIDS, persons infected with HIV had severe herpes outbreaks, which may have
helped them pass both genital herpes and HIV infection to others. As many as 1 in 5 people in the UK are infected with HHV-2 genital
herpes simplex.
Links:
http://herpesonline.org/HSV-1vs2.html
http://www.niaid.nih.gov/factsheets/stdherp.htm
- Genus: Varicellovirus
- Species:
Human herpesvirus 3
- Strain: Dumas
Genome accession number: X04370
EMBL reference
- Medline reference:
| Journal citation |
Pubmed ID |
| Science, 294 5550) 2317-23 (2001) |
11743193 |
- Taxonomy:
10335
HHV-3 is also known as Varicella Zoster Virus (VZV). VZV is an alphaherpesvirus that causes two
diseases, chickenpox and zoster (the reactivation of the virus that causes shingles). VZV was isolated and
characterised in 1958, although it has been recognised as the cause of both varicella (chicken pox) and herpes zoster (shingles) for
over 100 years. Both the active varicella and zoster form of the virus can cause chickenpox however the shingles virus in its latent
(inactive) form is never infectious.
More than 90% of the population develops a clinical or serological varicella infection by the time they reach adolescence,
and virtually 100% of the population will develop it by age 60. Most people get chickenpox from exposure to other people with
chicken pox. It is most often spread through sneezing, coughing, and breathing. It is so contagious that few non immunised people
escape this common disease when they are exposed to someone else with the disease. It can also be transmitted from direct contact
with the open sores. Varicella has a 14 day incubation period. Patients become contagious 2 days prior to the manifestation of the
rash, and remain so until all lesions are crusted. Chickenpox epidemics usually occur in late winter or early spring and is
characterised by a rash of itchy round or oval sores which at first look like pimples but will later blister and then crust over and heal.
When VZV reactivates, it is known as zoster. During their lifetimes, 10-20% of all people will develop zoster, and the
incidence increases dramatically with advanced age. VZV infections are medically significant, causing approximately 4 million
cases of varicella and 500,000 cases of zoster each year in the US. Unfortunately, many individuals will also develop post-herpetic
neuralgia, requiring long-term medical care. Zoster, also known as shingles, typically causes diffuse, varicella-like skin lesions,
most often on the chest and back. Patients usually experience pain in the areas that will be affected from 48-72 hours before the
lesions appear. In an immunocompetent individual, lesions form over a period of 3-5 days, and the disease lasts from 10-15 days.
In immunocompromised individuals, zoster can be much more serious.
The currently marketed varicella vaccines are based on the Oka strain of VZV which originated from Japan. It has been modified
through sequential propagation in different human and animal cell cultures. Various formulations of such live, attenuated vaccines
have been tested extensively and are approved for use in Japan, the Republic of Korea, the United States and several countries in
Europe. Varicella in persons who have received the vaccine ("break-through varicella") is substantially less severe than the disease
in unvaccinated individuals.
Links:
J. Gen. Virol. 67:1759-1816 (1986)
http://www.reutershealth.com/wellconnected/doc82.html
http://www.viracor.com/diagnostic-virals-vzv_overview.htm
http://virology-online.com/viruses/VZV.htm
- Genus: Lymphocryptovirus
- Species:
Human herpesvirus 4
- Strain: B95-8
Genome accession number: V01555
EMBL reference
- Medline references:
| Journal citation |
Pubmed ID |
| Nature 310(5974):207-211 (1984) |
6087149 |
| J. Cell. Biochem. 19(3):267-274 (1982) |
6296170 |
| Proc. Natl. Acad. Sci. U.S.A. 80(6):1565-1569 (1983) |
6300857 |
| EMBO J. 2(8):1331-1338 (1983) |
10872327 |
| Mol. Biol. Med. 1(1):21-45 (1983) |
6092825 |
| Mol. Biol. Med. 1(4):425-445 (1983) |
6094955 |
| EMBO J. 3(5):1083-1090 (1984) |
6203743 |
| Nucleic Acids Res. 12(12):5087-5099 (1984) |
6330697 |
| Nucleic Acids Res. 9(13):2999-3014 (1981) |
6269068 |
| Nucleic Acids Res. 9(20):5233-5252 (1981) |
7301588 |
| Proc. Natl. Acad. Sci. U.S.A. 81(12):3806-10 (1984) |
6328526 |
| EMBO J. 3(4):813-821 (1984) |
6327290 |
| J. Virol. 48(1):135-148 (1983) |
6310141 |
| Nucleic Acids Res. 15(14):5887 (1987) |
3039467 |
| EMBO J. 7(3):769-774 (1988) |
2840285 |
- Taxonomy:
10376
HHV-4 is also known as Epstein Barr Virus (EBV). EBV (HHV-4) is a gamma-herpesvirus that only naturally occurs
in humans. There are no animal reservoirs. EBV was named after Tony Epstein and Yvonne Barr who were the two scientists who first isolated
and described the virus in 1964 from lymphoma samples. Epstein-Barr virus (EBV) (HHV-4) is commonly known to cause infectious mononucleosis
(more commonly known as glandular fever or "kissing disease" because Epstein-Barr virus commonly is transmitted in saliva during
kissing). The virus occurs worldwide, and most people become infected with EBV sometime during their lives. In the United States, as many
as 95% ofadults between 35 and 40 years of age have been infected. Transmission of EBV requires intimate contact with the saliva of an
infected person. Transmission of this virus through the air or blood does not normally occur.
Symptoms of infectious mononucleosis are fever, sore throat, and swollen lymph glands. Sometimes, a swollen spleen or liver
involvement may develop. Heart problems or involvement of the central nervous system occurs only rarely, and infectious mononucleosis
is almost never fatal. Although the symptoms of infectious mononucleosis usually resolve in 1 or 2 months, EBV remains dormant or latent
in a few cells in the throat and blood for the rest of the person's life. There is no specific treatment for infectious mononucleosis,
other than treating the symptoms. No antiviral drugs or vaccines are available. However sometimes steroids are prescribed to control the
swelling of the throat and tonsils. Periodically, the virus can reactivate and it is commonly found in the saliva of infected persons.
This reactivation usually occurs without symptoms of illness.
EBV also establishes a lifelong dormant infection in some cells of the body's immune system. It has also been linked with
Burkitt's lymphoma, nasopharyngeal carcinoma and Hairy Leukoplakia.
Links:
Mol. Biol. Med. 1(3):369-392 (1983
http://bioserver.myongji.ac.kr/ebv.html
http://www.clevelandclinic.org/health/health-info/docs/1000/1042.asp?index=5926
http://www.cdc.gov/ncidod/diseases/ebv.htm
http://www.xtramsn.co.nz/health/0,,8065-3759138,00.html
- Genus: Cytomegalovirus
- Species:
Human herpesvirus 5
- Strain: AD169
Genome accession number: X17403
EMBL reference
- Medline references:
| Journal citation |
Pubmed ID |
| Curr. Top. Microbiol. Immunol. 154:125-169 (1990) |
2161319 |
| DNA Seq. 2(1):33-38 (1991) |
1666312 |
| DNA Seq. 2(1):1-12 (1991) |
1666311 |
- Taxonomy:
10359
HHV-5 is also known as Human Cytomegalovirus (CMV). CMV (HHV-5) is a beta-herpesvirus that only naturally
occurs in humans. The naming of CMV reflects that it tends to enlarge the cells that it infects (cyto = cell, mega = big). CMV is an
important human pathogen, particularly amongst immunocompromised patients including those who have AIDS or are immunosuppressed.
CMV, is found universally throughout all geographic locations and socioeconomic groups, and infects between 50% and 85%
of adults in the United States by 40 years of age. It is the virus most frequently transmitted to a developing child before birth.
For most healthy persons who acquire CMV after birth there are few symptoms and no long-term health consequences. Some persons
with symptoms experience a mononucleosis-like syndrome with prolonged fever, and a mild hepatitis. Once a person becomes infected,
the virus remains alive, but usually dormant within that person's body for life. Recurrent disease rarely occurs. Transmission
of CMV occurs from person to person. Infection requires close, intimate contact with a person excreting the virus in their
saliva, urine, or other bodily fluids. CMV can be sexually transmitted and can also be transmitted via breast milk, transplanted
organs, and rarely from blood transfusions. CMV has also been associated with Retinitis, Encephalitis, Esophagitis, Colitis and
Gastritis. There is no treatment for CMV infection.
Links:
http://www.cdc.gov/ncidod/diseases/cmv.htm
http://64.224.98.26/f-Oi/OppInfections/4-Viral/4-Vir-Cyto/4-Vir-Cyto.html
http://www.astdhpphe.org/infect/cytomegalo.html
- Genus: Roseolovirus
- Species:
Human herpesvirus 6
- Strain: U1102 variant A
Genome accession number: X83413
EMBL reference
- Medline references:
| Journal citation |
Pubmed ID |
| Virology 209 (1):29-51 (1995) |
7747482 |
| J. Virol. 64 (1):287-299 (1990) |
2152817 |
| J. Virol. 65 (6):2884-2894 (1991) |
1851860 |
| J. Virol. 65 (9):4670-4680 (1991) |
1651403 |
| Nature 351(6321):78-80 (1991) |
1851252 |
| J. Virol. 65(10):5381-5390 (1991) |
1654446 |
| J. Gen. Virol. 73:1661-1671 (1992) |
1321206 |
| J. Virol. 66(3):1564-1570 (1992) |
1310766 |
| DNA Seq. 3(1):25-39 (1992) |
1333836 |
| J. Virol. 66(6):3918-3924 (1992) |
1374813 |
| J. Gen. Virol. 73:1649-1660 (1992) |
1321205 |
| J. Gen. Virol. 74:495-500 (1993) |
8383182 |
| J. Gen. Virol. 74:613-622 (1993) |
8385692 |
| J. Gen. Virol. 74:1847-1857 (1993) |
8397282 |
| Virology 197(1):12-22 (1993) |
7692666 |
| Virology 195 (2):521-531 (1993) |
7687803 |
| J. Virol. 67(8):4611-4620 (1993) |
7687301 |
| J. Gen. Virol. 76:451-458 (1995) |
7844567 |
| J. Virol. 67(12):7680-7683 (1993) |
8230490 |
| J. Virol. 68 (2):597-610 (1994) |
8289364 |
| J. Virol. 68 (5):2978-2985 (1994) |
8151768 |
| Oncogene 9 (4):1167-1175 (1994) |
8134119 |
| Virology 199 (2):311-322 (1994) |
8122364 |
| J. Virol. 68 (5):3007-3014 (1994) |
8151770 |
| Virology 204 (1):304-311 (1994) |
8091661 |
| J. Virol. 68 (7):4126-4136 (1994) |
8207791 |
| Virology 197 (1):449-54 (1993) |
8212582 |
| J. Virol. 64 (2):714-722 (1990) |
2153237 |
| J. Gen. Virol. 72:157-168 (1991) |
1846644 |
| J. Gen. Virol. 70 ( 5) 1151-60 (1989) |
2543772 |
- Taxonomy:
10368
- Genus: Roseolovirus
- Species:
Human herpesvirus 6B
- Strain: Z29
Genome accession number: AF157706
EMBL reference
- Medline references:
| Journal citation |
Pubmed ID |
| Virology 195(2):521-531 (1993) |
7687803 |
| J. Virol. 69(1):589-596 (1995) |
7983761 |
| Arch. Virol. 141(2):367-379 (1996) |
8634027 |
| Arch. Virol. 142(1):103-123 (1997) |
9155876 |
| Arch. Virol. 142(1):193-204 (1997) |
9155884 |
| J. Virol. 73(10):8040-8052 (1999) |
1042553 |
- Taxonomy:
32604
HHV-6 was first discovered in 1986 in the United States at the National Cancer Institute. HHV-6 is the smallest of herpesviruses
(170 kb) and has been classified as beta-herpesvirus. This virus infects human white blood cells. HHV-6 has been identified as the
cause of childhood roseola (exanthem subitum). Symptoms of this illness include fever and a distinct type of rash. Most infants
are infected with HHV-6 before the age of two, but many display mild or no symptoms. Some symptoms, such as fever, may be incorrectly
attributed to conditions other than roseola. However, a small number of infected infants can develop serious disease including bone
marrow infection (decreased production of white blood cells and platelets) and brain infection (seizures).
Roseola is characterised by a fulminant, short-term fever that potentially reaches 40 Celsius and lasts for approximately
three days. Sore throat, local lymphadenopathy and development of a maculopapular skin rash over the trunk and neck, usually fading
without sequelae and sometimes absent are symptoms also associated with HHV-6 infection.
Two variants of HHV-6 are recognised: HHV-6A and HHV-6B. Primary infection of HHV-6B is the cause of roseola in children
and greater than 95% of the population has antibodies to this variant. Primary infection with HHV-6A is believed to occur later in
childhood or during adulthood and may occur without symptoms.
There is evidence for the association of HHV-6 with at least two other lymphoproliferative diseases , febrile illness in
young children, and EBV- and CMV- negative cases of mononucleosis in young adults. It may also be a cofactor in several other
diseases such as AIDS, cervical carcinoma, and oral carcinoma. HHV-6 is reactivated in infectious diseases, proliferative disorders,
and immune deficiencies. Data from a number of laboratories have suggested a role for HHV-6 in the pathogenesis of chronic fatigue
syndrome (CFS). Controversial new studies of HHV-6 are of interest to multiple sclerosis (MS) researchers because several studies
have found indicators of the virus to be significantly higher in people with MS (PwMS) than in control subjects.
Links:
J. Virol. 194:380-386 (1993)
http://www.wisconsinlab.com/hhv6.htm
http://www.hhv6.freeservers.com/
http://www.ccid.org/addviruses/hhv6.htm
http://www.mult-sclerosis.org/HumanHerpesVirus6.html
- Genus: Roseolovirus
- Species:
Human herpesvirus 7
- Strain: RK
Genome accession number: AF037218
EMBL reference
- Medline reference:
| Journal citation |
Pubmed ID |
| Virology 244(1):119-132 (1998) |
9581785 |
- Taxonomy:
10372
FHHV-7 was discovered four years after the isolation of HHV-6. Because of the similarities in genes and gene products between
HHV-6 and HHV-7 some cross-reactivity have been noted. It is not known whether it causes any disease. HHV-7 is similar to human
herpesvirus 6 (HHV-6) in its genetic content and in many of its biological properties, which include the ability to cause at least some
cases of roseola (exanthem subitum).
Links:
http://www.emergingworlds.com/ch_viruses_detail.cfm?vPageid=115
References:
http://web.uct.ac.za/depts/mmi/jmoodie/herpes2.html
http://www-micro.msb.le.ac.uk/3035/Herpesviruses.html
http://www.medterms.com/script/main/art.asp?articlekey=11496
http://darwin.bio.uci.edu/~faculty/wagner/
http://www.edcp.org/factsheets/herpes.html
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