Herpesvirus Infections


There are 80 known herpesviruses, and eight of them are known to cause infection in humans: herpes simplex virus (HSV) 1 and 2, varicella-zoster virus, Cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 (HHV6). All herpesviruses contain a deoxyribonucleic acid (DNA) nucleus and can remain latent in host neural cells, thereby evading the host immune response.HHV6, a herpesvirus discovered in 1986, has been shown by seroprevalence studies to infect over 80% of the population by adult life. Two variants, HHV6A and HHV6B have been identified.
The virus is commonly isolated from saliva and causes roseola infantum (exanthema subitum), a common childhood illness that is characterized by fever and a rash. The virus also is a cause of a mononucleosislike syndrome in older children and adults. In immunocompromised patients, HHV6 can cause interstitial pneumonitis and bone marrow suppression.HHV7, which is commonly isolated from saliva, is presently not associated with a specific disease, whereas HHV8 has been closely associated with Kaposi’s sarcoma in human immunodeficiency virus (HIV)infected patients. There is also evidence linking HHV8 to forms of lymphoma and Castleman’s disease.
HSV1, HSV2, and varicella-zoster are viruses that are known to cause oral mucosal disease. Cytomegalovirus is an occasional cause of oral ulceration in immunosuppressed patients, and it is suspected as a cause of salivary gland disease in HIV-infected patients.
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The herpes simplex virus is composed of four layers: an inner core of linear double-stranded DNA, a protein capsid, a tegument, and a lipid envelope containing glycoproteins that is derived from the nuclear membrane of host cells. The two major types, HSV1 and 2, can be distinguished serologically or by restriction endonuclease analysis of the nuclear DNA. Classically, HSV1 causes a majority of cases of oral and pharyngeal infection, meningoencephalitis, and dermatitis above the waist; HSV2 is implicated in most genital infections. Although this distinction applies to a majority of cases, changing sexual habits are making that distinction less important. Both types can cause primary or recurrent infection of either the oral or the genital area, and both may cause recurrent disease at either site.Primary infection may also occur concurrently in both oral and genital sites from either HSV1 or HSV2,although HSV1 recurs more frequently in the oral region and HSV2 more frequently in the genital region.
Humans are the only natural reservoir of HSV infection, and spread occurs by direct intimate contact with lesions or secretions from an asymptomatic carrier. This latter method of spread of HSV is common; between 2 and 9% of asymptomatic individuals shed HSV in saliva or genital secretions.
Latency, a characteristic of all herpesviruses, occurs when the virus is transported from mucosal or cutaneous nerve endings by neurons to ganglia where the HSV viral genome remains present in a nonreplicating state.During the latent phase, herpes DNA is detectable, but viral proteins are not produced.Reactivation of the latent virus occurs when HSV switches to a replicative state; this can occur as a result of anumber of factors including peripheral tissue injury from trauma or sunburn, fever, or immunosuppression.
The concept that HSV is a possible cause of Bell’s palsy was initially suggested in 1972,but recent evidence using genetic and molecular techniques has demonstrated that reactivation of HSV is the most common cause of this disorder.
There is evidence linking HSV to carcinogenesis.
Epidemiologic studies have demonstrated an increased incidence of HSV2 serum antibodies or positive HSV2 cultures in patients with cervical carcinoma. Animal studies on hamster cheek pouches show an enhanced development of invasive squamous cell carcinoma when HSV1 infection is combined with topical snuff.