Medical biology, microbiology, virology, immunology department HERPESVIRUSES. By as. E.V. Pokryshko Properties of the Viruses: All herpesviruses have a core of double-stranded DNA surrounded by a protein coat that exhibits icosahedral symmetry. The nucleocapsid is surrounded by an envelope. Common and important herpesviruses of humans include herpes simplex virus types 1 and 2, varicella-zoster virus, EpsteinBarr (EB) virus, and cytomegalovirus. HERPES SIMPLEX: Human Herpesvirus 1 (Herpes Labialis) & Human Herpesvirus 2 (Herpes Genitalis). Infection with herpes simplex virus may take several clinical forms. The infection is most often inapparent. The usual clinical manifestation is a vesicular eruption of the skin or mucous membranes. Infection is sometimes seen as severe keratitis, meningoencephalitis, and a disseminated illness of the newborn. Cytopathic effect (infected cells develop intranuclear acidophilic inclusion and then undergo necrosis ) Herpes labialis (cold sores, herpes febrilis). This is the most common recurrent disease produced by type 1. Clusters of localized vesicles occur, usually at the mucocutaneous junction of the lips. The vesicle ruptures, leaving a painful ulcer that heals without scarring. The lesions may recur, repeatedly and at various intervals of time, in the same location. The permanent site of latent herpes simplex virus is the trigeminal ganglion. Herpes labialis Keratoconjunctivitis. The initial infection with herpesvirus may be in the eye, producing severe keratoconjunctivitis. Recurrent lesions of the eye appear as dendritic keratitis or corneal ulcers or as vesicles on the eyelids. With recurrent keratitis, there may be progressive involvement of the corneal stroma, with permanent opacification and blindness. Genital herpes (herpes progenitalis). Genital herpes is characterized by vesiculoulcerative lesions of the penis of the male or the cervix, vulva, vagina, and perineum of the female. The lesions are more severe during primary infection and may be associated with fever, malaise, and inguinal lymphadenopathy. Type 2 virus remains latent in lumbar and sacral ganglia. Neonatal herpes. Herpesvirus type 2 may be transmitted to the newborn during birth by contact with herpetic lesions in the birth canal. The spectrum of illness produced in the newborn appears to vary from subclinical or local to severe generalized disease with a fatal outcome. Severely affected infants who survive may have permanent brain damage. Laboratory Diagnosis The virus may be isolated from herpetic lesions (skin, cornea, or brain). The appearance of typical cytopathic effects in cell culture suggests the presence of herpesvirus in 18-36 hours. Scrapings or swabs from the base of early herpetic lesions contain multinucleated giant cells. Serology: The agent is then identified by neutralization test or immunofluorescence staining with specific antiserum. Antibodies appear in 4-7 days; can be measured by NT, IHT, CFT, RIA and reach a peak in 2-4 weeks. HV, immune fluorescence test VARICELLA-ZOSTER VIRUS (Human Herpesvirus 3) (Chickenpox, Herpes Zoster, Shingles, Zona) Varicella (chickenpox) is a mild, highly infectious disease, chiefly of children, characterized clinically by a vesicular eruption of the skin and mucous membranes. The causative agent is indistinguishable from the virus of zoster. Zoster (shingles) is a sporadic, incapacitating disease of adults (rare in children) that is characterized by an inflammatory reaction of the posterior nerve roots and ganglia, accompanied by crops of vesicles (like those of varicella) over the skin supplied by the affected sensory nerves. VARICELLA-ZOSTER VIRUS (Human Herpesvirus 3) (Chickenpox, Herpes Zoster, Shingles, Zona) Both diseases are caused by the same virus. Varicella is the acute disease that follows primary contact with the virus, whereas zoster is the response of the partially immune host to a reactivation of varicella virus present in latent form in sensory ganglia. Pathogenesis & Pathology. Varicella: The route of infection is probably the mucosa of the upper respiratory tract. The virus probably circulates in the blood and localizes in the skin. Swelling of epithelial cells, ballooning degeneration, and the accumulation of tissue fluids result in vesicle formation. In nuclei of infected cells, particularly in the early stages, eosinophilic inclusion bodies are found. Varicella virus, pathogenesis Varicella Chickenpox Pathogenesis & Pathology. Zoster: In addition to skin lesions — histopathologically identical with those of varicella — there is an inflammatory reaction of the dorsal nerve roots and sensory ganglia. Often only a single ganglion may be involved. As a rule, the distribution of lesions in the skin corresponds closely to the areas of innervation from an individual dorsal root ganglion. There is cellular infiltration, necrosis of nerve cells, and inflammation of the ganglion sheath. Zoster Shingles CYTOMECALOVIRUS (Human Herpesvirus 5) Cytomegalic inclusion disease is a generalized infection of infants caused by intrauterine or early postnatal infection with the cytomegaloviruses. The disease causes severe congenital anomalies. Cytomegalovirus can be found in the cervix of up to 10% of healthy women. Cytomegalic inclusion disease is characterized by large intranuclear inclusions that occur in the salivary glands, lungs, liver, pancreas, kidneys, endocrine glands, and occasionally, the brain. Most fatalities occur in children under 2 years of age. Inapparent infection is common during childhood and adolescence. Severe cytomegalovirus infections are frequently found in adults receiving immunosuppressive therapy. Cytomegalovirus Inclusion Diseases. Electron micrograph of a single animal cell infected with the cytomegalovirus. The intranuclear inclusion body has a typical” owl-eyed” apearence. Pathogenesis. Cytomegalovirus can cause persistent infection in various tissues, including those of the salivary glands, breasts, kidneys, endocervix, seminal vesicles and peripheral blood leukocytes. This persistent infection leads to chronic viral excretion by the involved organ. Transmission of virus is through contact with infected secretions. The average incubation period is four to six weeks. It should also be noted that the kidneys of organ donors can be a source of cytomegalovirus for the recipient, and that peripheral blood leukocytes have been implicated in the transmission of cytomegalovirus via blood transfusion. Clinical Manifestations. Cytomegalovirus infection can result in one of three distinct clinical syndromes. Congenital cytomegalovirus infection: hepatospleno-megaly, retinitis, a petechial/purpuric skin rash, and involvement of the central nervous system (ventriculo-megaly, intracranial calcifications, etc). Clinical Manifestations. Mononucleosis syndrome (fever, malaise, atypical lymphocytosis, pharyngitis and, rarely, cervical adenopathy or hepatitis) Third clinical entity is cytomegalovirus infection in severely immunocompromised individuals. In these patients, infection can involve the lungs, gastrointestinal tract, liver, retina, and central nervous system EB HERPESVIRUS (Human Herpesvirus 4). EB (Epstein-Barr) virus is the causative agent of infectious mononucleosis and has been associated with Burkitt's lymphoma and nasopharyngeal carcinoma. Epidemiology. Epstein-Barr virus is transmitted by intimate contact. Pathogenesis. Epstein-Barr virus is tropic for Blymphocytes. Infectious mononucleosis Nasopharyngeal carcinoma Burkitt's lymphoma Oncogenic Properties: Herpesviruses have been linked with malignant diseases in humans : herpes simplex virus type 2 with cervical and vulvar carcinoma; EB virus with Burkilt 's lymphoma of African children and with nasopharyngeal carcinoma. QUESTIONS?