Herpesviruses have a unique four-layered structure: a core containing the large, double-stranded DNA genome is enclosed by an icosapentahedral capsid which is composed of capsomers. The capsid is surrounded by an amorphous protein coat called the tegument. It is encased in a glycoprotein-bearing lipid bilayer envelope. Transcription, genome replication, and capsid assembly occur in the host cell nucleus.
Genes are replicated in a specific order: 1 immediate-early genes, which encode regulatory proteins; 2 early genes, which encode enzymes for replicating viral DNA; and 3 late genes, which encode structural proteins. The tegument and envelope are acquired as the virion buds out through the nuclear membrane or endoplasmic reticulum.
Virions are transported to the cell membrane via the Golgi complex, and the host cell dies as mature virions are released. Alternatively, in selected cell types, the virus may be maintained in a latent state. The latent viral genome may reactivate at any time; the mechanism of reactivation is not known. Cytomegalovirus retinitis is diagnosed clinically.
Prevention: A vaccine to prevent varicella-zoster virus infections was recently licensed in the United States. Vaccines against herpes simplex virus 2, and cytomegalovirus are undergoing extensive evaluations in field trials. Passive immunization with immunoglobulin or hyperimmune globulin is used either to prevent infection or as an adjunct to antiviral therapy.
Treatment: Infections with herpes simplex virus 1 and 2 and varicella-zoster virus are currently the most amenable to therapy; acyclovir, valaciclovir and famciclovir are all licensed therapeutics.
Ganciclovir is used to treat cytomegalovirus retinitis. B virus appears to respond to either of these drugs.
There is as yet no treatment for Epstein-Barr virus or human herpesvirus 6,7 or 8 infections. Herpes simplex viruses 1 and 2 have only about 50 percent genomic homology.
However, they share most other characteristics. Mucocutaneous manifestations of herpes simplex virus infection include gingivostomatitis, herpes genitalis, herpetic keratitis, and dermal whitlows.
Neonatal herpes simplex virus infection and herpes simplex virus encephalitis also occur. The virus replicates initially in epithelial cells, producing a characteristic vesicle on an erythematous base.
It then ascends sensory nerves to the dorsal root ganglia, where, after an initial period of replication, it establishes latency. Interferon and humoral, mucosal, and cellular immunity are important defenses. Herpes simplex virus infections are more severe in immunocompromised hosts. Herpes simplex virus 1 transmission is primarily oral, and herpes simplex virus 2 primarily genital. Transmission requires intimate contact. Primary varicella-zoster virus infection causes varicella chickenpox.
Reactivation of latent virus usually in adults causes herpes zoster shingles , manifesting as vesicular rash with a dermatomal distribution and acute neuritis. Varicella-zoster virus is usually transmitted by droplets and replicates initially in the nasopharynx. In seronegative individuals, viremia and chickenpox ensue. Latency is established in dorsal root ganglia, and virus reactivation results in virion transport down sensory nerves.
As with herpes simplex virus, interferon and cellular and humoral immunity are important defenses. Reactivated virus can cause disseminated disease in immunocompromised individuals. Varicella-zoster virus is highly contagious; about 95 percent of adults show serologic evidence of infection.
Cytomegalovirus causes three clinical syndromes. Cytomegalovirus replicates mainly in the salivary glands and kidneys and is shed in saliva and urine. Replication is slow, and the virus induces characteristic giant cells with intranuclear inclusions. Transmission is via intimate contact with infected secretions.
Cytomegalovirus infections are among the most prevalent viral infections worldwide. Epstein-Barr virus causes classic mononucleosis. In immunocompromised hosts, the virus causes a lymphoproliferative syndrome. In some families, Epstein Barr virus causes Duncan's syndrome. Human herpes viruses 6 and 7 are associated with exanthem subitem roseola and with rejection of transplanted kidneys. Human herpesvirus 8 has been found associated with Kaposi's sarcoma in AIDS patients as well as intra-abdominal solid tumors.
Virtually nothing is known about the pathogenesis and epidemiology of this newly described herpesvirus. B virus is transmitted to humans by the bite of infected rhesus monkeys and is transported up neurons to the brain. The reservoir for the disease is latent infection in rhesus monkeys, particularly those from Southeast Asia and India.
In stressed or unhealthy animals, the virus may reactivate and appear in saliva. In nature, herpesviruses infect both vertebrate and non-vertebrate species, and over a hundred have been at least partially characterized. Only eight of these have been isolated routinely from humans and are discussed here. They are known as the human herpesviruses and are herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, human herpesvirus 7 and, most recently, Kaposi's Sarcoma herpesvirus.
A primate herpesvirus, namely B virus, is an uncommon human pathogen that may cause life-threatening disease. The human herpesviruses share four significant biologic properties. First, all of the herpesviruses code for unique enzymes involved in the biosynthesis of viral nucleic acids. These enzymes are structurally diverse and parenthetically provide unique sites for inhibition by antiviral agents. Secondly, the synthesis and assembly of viral DNA is initiated in the nucleus.
Assembly of the capsid is also initiated in the nucleus. Third, release of progeny virus from the infected cell is accompanied by cell death. Finally, all herpesviruses establish latent infection within tissues that are characteristic for each virus, reflecting the unique tissue trophism of each member of this family. Membership in the family Herpesviridae is based on the structure of the virion. These viruses contain double-stranded DNA which is located at the central core. The precise arrangement of the DNA within the core is not known.
Herpesvirus DNA varies in molecular weight from approximately 80 to million, or to kilobase pairs, depending on the virus. This DNA core is surrounded by a capsid which consists of capsomers, arranged in icosapentahedral symmetry. The capsid is approximately to nanometers in diameter. Tightly adherent to the capsid is the tegument, which appears to consist of amorphous material.
Loosely surrounding the capsid and tegument is a lipid bilayer envelope derived from host cell membranes. The envelope consists of polyamines, lipids, and glycoproteins. These glycoproteins confer distinctive properties to each virus and provide unique antigens to which the host is capable of responding. A fascinating feature of herpesvirus DNA is its genomic sequence arrangement. Herpesviruses can be divided into six groups arbitrarily classified A to F.
For those herpesviruses which infect humans group C, group D, and group E unique structures are demonstrable. In the group C genomes, as exemplified by Epstein-Barr virus and the newly identified Kaposi's sarcoma herpesvirus, the number of terminal reiterations divides the genome into several well-delineated domains.
The group D genomes, such as varicella-zoster virus, have sequences from one terminus repeated in an inverted orientation internally. Thus, the DNA extracted from these virions consist of two equal molar populations.
For group E viral genomes, such as herpes simplex virus and cytomegalovirus, the genomes are divided into internal unique sequences whereby both termini are repeated in an inverted orientation.
Thus, the genomes can form four equimolar populations which differ in relative orientation of the two unique segments. The grouping of herpesviruses into sub-families serves the purpose of identifying evolutionary relatedness as well as summarizing unique properties of each member.
The members of the alpha herpesvirus sub-family are characterized by an extremely short reproductive cycle hours , prompt destruction of the host cell, and the ability to replicate in a wide variety of host tissues. They characteristically establish latent infection in sensory nerve ganglia. This sub-family consists of herpes simplex virus 1 and 2 and varicella-zoster virus.
In contrast to the alpha herpesviruses, beta herpesviruses have a restricted host range. Their reproductive life cycle is long days , with infection progressing slowly in cell culture systems. A characteristic of these viruses is their ability to form enlarged cells, as exemplified by human cytomegalovirus infection. These viruses can establish latent infection in secretory glands, cells of the reticuloendothelial system, and the kidneys.
Finally, the gamma herpesviruses have the most limited host range. They replicate in lymphoblastoid cells in vitro and can cause lytic infections in certain targeted cells.
Latent virus has been demonstrated in lymphoid tissue. Epstein-Barr virus is a member of this sub-family. In addition, human herpesvirus 6 and 7 are probably best classified as a gamma herpesvirus. However, the latter has host range properties of the beta sub-family. Further studies will need to clarify the most appropriate classification of this virus.
Kaposi's sarcoma herpesvirus is most closely related genetically to Epstein-Barr virus. Replication of all herpesviruses is a multi-step process. Following the onset of infection, DNA is uncoated and transported to the nucleus of the host cell. This is followed by transcription of immediate-early genes, which encode for the regulatory proteins.
Expression of immediate-early gene products is followed by the expression of proteins encoded by early and then late genes. Assembly of the viral core and capsid takes place within the nucleus. This is followed by envelopment at the nuclear membrane and transport out of the nucleus through the endoplasmic reticulum and the Golgi apparatus.
Glycosylation of the viral membrane occurs in the Golgi apparatus. Mature virions are transported to the outer membrane of the host cell inside vesicles.
Release of progeny virus is accompanied by cell death. Replication for all herpesviruses is considered inefficient, with a high ratio of non-infectious to infectious viral particles. A unique characteristic of the herpesviruses is their ability to establish latent infection.
Each virus within the family has the potential to establish latency in specific host cells, and the latent viral genome may be either extra-chromosomal or integrated into host cell DNA.
Herpes simplex virus 1 and 2 and varicella-zoster virus all establish latency in the dorsal root ganglia. Epstein-Barr virus can maintain latency within B lymphocytes and salivary glands.
Cytomegalovirus, human herpesvirus 6 and 7, Kaposi's sarcoma herpesvirus and B virus have unknown sites of latency. Latent virus may be reactivated and enter a replicative cycle at any point in time. The reactivation of latent virus is a well-recognized biologic phenomenon, but not one that is understood from a biochemical or genetic standpoint. It should be noted here that an anti-sense message to one of the immediate-early genes alpha-O may be involved in the maintenance of latent virus.
Stimuli that have been observed to be associated with the reactivation of latent herpes simplex virus have included stress, menstruation, and exposure to ultraviolet light. Precisely how these factors interact at the level of the ganglia remains to be defined. It should be noted that reactivation of herpesviruses may be clinically asymptomatic, or it may produce life-threatening disease. With the exception of cytomegalovirus retinitis, the definitive diagnosis of a herpesvirus infection requires either isolation of virus or detection of viral gene products.
For virus isolation, swabs of clinical specimens or other body fluids can be inoculated into susceptible cell lines and observed for the development of characteristic cytopathic effects.
This technique is most useful for the diagnosis of infection due to herpes simplex virus 1 and 2 or varicella-zoster virus because of their relatively short replicative cycles.
The identification of cytomegalovirus by cell culture requires a longer period of time due to its prolonged period of replication. Epstein-Barr virus does not induce cytopathic changes in cell culture systems and, therefore, can only be identified in culture by transformation of cord blood lymphocytes.
Similarly, human herpes virus 6 and 7 have unique growth characteristics which make identification in cell culture systems difficult. Newer and more rapid diagnostic techniques involve the detection of viral gene products.
This can be done by applying fluorescence antibody directed against immediate-early or late gene products to tissue cultures after 24 to 72 hours of incubation. A positive result is the appearance of intranuclear fluorescence. A method which utilizes monoclonal antibodies to an immediate-early gene has been most useful for the identification of CMV. Alternatively, fluorescence antibodies may be applied directly to cell monolayers or scrapings of clinical lesions, with intranuclear fluorescence again indicating a positive result.
Recently developed diagnostic techniques that have clinical utility include in situ and dot-blot hybridization and, importantly, polymerase chain reaction DNA amplification. This latter technique has proved most successful in the diagnosis of herpes simplex virus infections of the central nervous system, particularly when applied to cerebrospinal fluid. Importantly, this tool has been utilized to study the natural history of genital herpes simplex virus infections as well as identify new herpesvirus infections i.
Kaposi's sarcoma herpesvirus. In addition to new tests for virus gene products and viral DNA, improved serologic assays are also becoming available, particularly the application of immunoblot technology to distinguishing herpes simplex virus 1 from 2 infections. However, these tests are only useful for making a diagnosis in retrospect. Finally, the diagnosis of cytomegalovirus retinitis deserves special mention because it is made clinically by the presence of characteristic retinal changes.
The diagnosis is further supported by the presence of cytomegalovirus viruria or viremia, but this is not an absolute requirement. Of all the herpesviruses, herpes simplex virus type 1 and herpes simplex virus type 2 are the most closely related, with nearly 70 per cent genomic homology. These two viruses can be distinguished most reliably by DNA composition; however, differences in antigen expression and biologic properties also serve as methods for differentiation. A critical factor for transmission of herpes simplex viruses, regardless of virus type, is the requirement for intimate contact between a person who is shedding virus and a susceptible host.
After inoculation onto the skin or mucous membrane and an incubation period of four to six days, herpes simplex virus replicates in epithelial cells Figure As replication continues, cell lysis and local inflammation ensue, resulting in characteristic vesicles on an erythematous base.
Regional lymphatics and lymph nodes become involved: viremia and visceral dissemination may develop depending upon the immunologic competence of the host. In all hosts, the virus generally ascends the peripheral sensory nerves to reach the dorsal root ganglia. Replication of herpes simplex virus within neural tissue is followed by retrograde axonal spread of the virus back to other mucosal and skin surfaces via the peripheral sensory nerves.
Virus replicates further in epithelial cells, reproducing the lesions of the initial infection, until infection is contained through both systemic and mucosal immunity. Latency is established when herpes simplex virus reaches the dorsal root ganglia after anterograde transmission via sensory nerve pathways. In its latent form, intracellular herpes simplex virus DNA cannot be detected routinely unless specific molecular probes are utilized. Mucocutaneous infections are the most common clinical manifestations of herpes simplex virus 1 and 2.
Gingivostomatitis, which is usually caused by herpes simplex virus 1, occurs most frequently in children less than five years of age. Gingivostomatitis is characterized by fever, sore throat, pharyngeal edema and erythema, followed by the development of vesicular or ulcerative lesions on the oral and pharyngeal mucosa.
Recurrent herpes simplex virus 1 infections of the oropharynx most frequently manifest as herpes simplex labialis cold sores , and usually appear on the vermillion border of the lip.
Intraoral lesions as a manifestation of recurrent disease are uncommon in the normal host but do occur frequently in immunocompromised individuals. Genital herpes is most frequently caused by herpes simplex virus 2 but an ever increasing number of cases are attributed to herpes simplex virus 1. Primary infection in women usually involves the vulva, vagina, and cervix Figure In men, initial infection is most often associated with lesions on the glans penis, prepuce or penile shaft.
In individuals of either sex, primary disease is associated with fever, malaise, anorexia, and bilateral inguinal adenopathy. Having sores or other symptoms of herpes can increase your risk of spreading the disease. Even if you do not have any symptoms, you can still infect your sex partners.
You may have concerns about how genital herpes will impact your health, sex life, and relationships. While herpes is not curable, it is important to know that it is manageable with medicine. Daily suppressive therapy i. Talk to a healthcare provider about your concerns and treatment options.
A genital herpes diagnosis may affect how you will feel about current or future sexual relationships. Knowing how to talk to sexual partners about STDs external icon is important.
Herpes infection can cause sores or breaks in the skin or lining of the mouth, vagina, and rectum. This provides a way for HIV to enter the body. Even without visible sores, herpes increases the number of immune cells in the lining of the genitals. HIV targets immune cells for entry into the body. Box Rockville, MD E-mail: npin-info cdc. Skip directly to site content Skip directly to page options Skip directly to A-Z link. Genital Herpes.
Section Navigation. Facebook Twitter LinkedIn Syndicate. Minus Related Pages. People who are sexually active can get genital herpes, a common sexually transmitted disease STD. What is genital herpes? What is oral herpes? Is there a link between genital herpes and oral herpes? How common is genital herpes? You can get herpes if you have contact with: A herpes sore; Saliva from a partner with an oral herpes infection; Genital fluids from a partner with a genital herpes infection; Skin in the oral area of a partner with oral herpes; or Skin in the genital area of a partner with genital herpes.
How do I know if I have genital herpes? How will my healthcare provider know if I have genital herpes? Have an honest and open talk with your healthcare provider about herpes testing and other STDs. How can I prevent genital herpes? The only way to completely avoid STDs is to not have vaginal, anal, or oral sex.
If you are sexually active, you can do the following things to lower your chances of getting genital herpes: Being in a long-term mutually monogamous relationship with a partner who does not have herpes. Using condoms the right way every time you have sex.
This is something your partner should discuss with his or her healthcare provider. You avoid having vaginal, anal, or oral sex when your partner has herpes symptoms i. I knew a girl who had an HSV-2 infection on her finger. Another had it on her lower leg.
It is a virus, so when your immune system is down, you will be more likely to have an outbreak. Which makes it spread like crazy. Even people that have it can take an antiviral pill that will make transmission harder. But if no one knows, it keeps spreading. HSV-1 is an infection in your lips which you can contract by simply touching virus to your mouth by kissing someone with a sore or is about to get one. HSV-2 is genital warts which you contract through sex, but recently they have discovered than the 2 strains can be found in opposite places.
I think the transmission is self explanatory. Everyone Has a Herpes Virus Did you know that you most likely have live viruses hiding in your nerves and central nervous system? Again, even if you do not have any symptoms the virus can still be present in your body. November 7, Categories Class of
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