Herpes Viruses
CMV & EBV Outline
Latent Infections
- ALL herpes viruses can establish latent infections. The viral genome may become incorporated into the host DNA or remain extrachromosomal
- Latent viruses can be reactivated by stress, menstruation or uv light
- Reactivation may be asymptomatic or lead to mild or severe disease.
Herpes Diagnosis
- Isolation of virus by tissue culture
- herpevirinae cause cytopathic effects
- intranuclear fluorescence of scrapings using fluorescent antibodies
CMV retiniitis is diagnosed clinically
Epstein Barr Virus
Epstein-Barr virus
- virus established in lymphoid tissue and salivary glands - is excreted from salivary glands.
- Epstein-Barr virus is a transforming DNA virus.
EBV History
- infectious mononucleosis, first described more than 100 years ago.
- in 1958, Michael Burkitt discovered that a malignant tumour, Burkitt’s lymphoma, was infectious.
- in 1959, Michael Epstein and Yvonne Barr cultured a virus from tumours that showed typical herpes-like morphology.
EBV and Burkitt’s lymphoma were shown to be the same virus when a lab technician acquired mononucleosis while working with the Burkitt’s lymphoma virus.
EBV Diseases
- lymphoproliferative cancer in heart and bone marrow transplant recipients
- Burkitt’s lymphoma (B cell carcinoma) in E. africans
- nasopharyngeal carcinoma in Chinese
Classic Mononucleosis
- infectious mononucleosis has an incubation period of 30 to 50 days.
- high fever, malaise, myalgia, cervical lymphadenopathy, splenomegaly, hepatomegaly
- high fever, pharyngitis, grey-white pharyngeal exudate, skin rash
- atypical lymphocytosis or leucocytosis: infected B cells, T cells (suppresser and cytotoxic)
- recover due to a strong cell-mediated response
Complications
- Carcinoma
- Burkitt’s lymphoma (B cell carcinoma)
- Nasopharyngeal carcinoma.
- if there is an immune deficiency especially of T cells - the host is highly susceptible to Epstein-Barr virus.
Infectious Mononucleosis Diagnosis
- differential blood count - lymphocytosis, neutropenia, large atypical cells.
- antibodies to EBV nuclear antigen
- antibodies to EBV capsid antigen
Infectious Mononucleosis Transmission
Exposure
- early in Africa and Asia, later in industrialized countries
- 70% of college age persons have never had exposure - very susceptible to the virus.
- 95% of middle aged adults are seropositive.
Portal of Entry
- attaches to the epithelium
- moves to the Parotid gland
- latent in throat and blood
Epstein-Barr Virus - Symptoms
- sore throat, high fever, cervical lymphadenopathy, grey-white pharyngeal exudate, skin rash, enlarged liver and spleen.
- Leucocytosis: infected B cells, T cells (suppresser and cytotoxic)
- recover due to a strong cell-mediated response (T cell).
Cancer
- Transformation of the cell by virus
- Helper virus if the transforming virus is defective
- Co-carcinogen, chemical, cigarette smoke
Transformed cells:
- lose contact inhibition
- continue to divide
- form random aggregations
- can become invasive
Primary Hepatocellular Carcinoma
- Icteric symptoms:
- jaundice, dark urine, pale stools
- Highest incidence:
- Central Africa
- Southeast China
- Pacific Islands, Borneo, Sarawak, Taiwan
- 250,000 to1,000,000 deaths worldwide per year
- U.S.A. 5000 deaths / year
Human T-cell Leukemia Virus
- retroviruses with no oncogenes
- Adult T-cell leukemia and lymphoma - Southern Japan, Carribean Islands, West Africa
Epstein Barr
- suspect co-carcinogen: - nitrosamines in salted fish
Burkitts Lymphoma
- East Africa, Papua New Guinea
- at risk: 6 -14 year old males
- tumor of immature B-cells
Human Papillomavirus
- cervical, penile, vulval, and rectal cancer
- viral genome integrated into host genome
- Co-carcinogens - cigarette smoke - HSV herpes
Cytomegalovirus
Cytomegalovirus
Intranuclear inclusions
- The cell swells and a large inclusion body forms in the nucleus.
Cytomegalovirus
- Nuclear & cytoplasmic inclusions
Transmission: CMV
- not highly infectious, virus found in saliva, urine and blood.
- infants and children acquire CMV from other children.
- congenital. In utero, at birth during perinatal period.
Congenital: CMV
- the following possibilities relate to the congenital type.
- severe deformities and death.
- survive with serious defects - physical and mental.
- survive with out deformities.
- newborns: - Enlarged liver and spleen, jaundice, capillary bleeding, microcephaly, ocular inflammation.
Disseminated cytomegalovirus
- fever, severe diarrhea, hepatitis, arthritis, pneumonia, high mortality.
- activation of inapparent infection.
- also due to:
- immunosuppressive therapy.
- cancer.
- AIDS.
Virus in blood or organ:
Cytomegalovirus mononucleosis:
- teenage, young adult similar to other mono.
Transmission:
- saliva, respiratory mucus, milk, urine, semen, cervical secretions, feces and lymphocytes.
Differential Diagnosis:
- the differential diagnosis in neonates must include toxoplasmosis, rubella, herpes simplex, bacterial sepsis.
- in adults it must be differentiated from Epstein-Barra and hepatitis A & B.
Laboratory diagnosis: CMV
- virus can be grown from all organs.
Treatment: CMV
- gancyclovir, foscarnet, hyperimmune CMV immunoglobulin, have some effect.
- interferon does not prevent infection or promote recovery.
Prevention:CMV
- no animal can be found that can be infected with CMV.
- vaccine stimulated antibodies may not be protective. Patients already seropositve can be reinfected.
- a vaccine could be oncogenic.
Epidemiology of CMV
- 40-100% positive for the antibodies.
- newborns 7.5% positive in the USA & UK.
- woman of child bearing age were 20-100% positive in many countries that were studied (pregnant - virus in the urine).
- IV drug users were 100% positive for the antibodies.
- homosexual males were 30% positive for the antibodies - high percentage shed virus.