Herpes Viruses

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Herpes Viruses

• Epstein-Barr virus
• Cytomegalovirus

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CMV EBV Outline

• Structure
• Classification
• Multiplication
• Clinical manifestations
• Epidemiology
• Diagnosis
• Control

Barons Web Site
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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.

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Herpes Diagnosis

• Isolation of virus by tissue culture
• herpevirinae cause cytopathic effects
• intranuclear fluorescence of scrapings using
  fluorescent antibodies
• PCR being developed

CMV retiniitis is diagnosed clinically
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Epstein Barr Virus
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Epstein-Barr virus

• virus established in lymphoid tissue and salivary
  glands - is excreted from salivary glands.
• Epstein-Barr virus is a transforming DNA virus.

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EBV History

• infectious mononucleosis, first described more
  than 100 years ago.
• in 1958, Michael Burkitt discovered that a
  malignant tumour, Burkitts lymphoma, was
  infectious.
• in 1959, Michael Epstein and Yvonne Barr cultured
  a virus from tumours that showed typical
  herpes-like morphology.

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EBV and Burkitts lymphoma were shown to be the
same virus when a lab technician acquired
mononucleosis while working with the Burkitts
lymphoma virus.
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EBV Diseases

• Infectious mononucleosis
• lymphoproliferative cancer in heart and bone
  marrow transplant recipients
• Burkitts lymphoma (B cell carcinoma) in E.
  africans
• nasopharyngeal carcinoma in Chinese

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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

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Complications

• Carcinoma
• Burkitts 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.

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Infectious MononucleosisDiagnosis

• clinical symptoms
• differential blood count - lymphocytosis,
  neutropenia, large atypical cells.
• heterophile antibodies
• antibodies to EBV nuclear antigen
• antibodies to EBV capsid antigen

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Infectious MononucleosisTransmission

• direct oral contact
• exposure to saliva
• fomites
• arthropod vectors

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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.

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Portal of Entry

• oropharynx
• attaches to the epithelium
• moves to the Parotid gland
• viremia
• latent in throat and blood
• subclinical asymptomatic

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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).

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Cancer

• Transformation of the cell by virus
• Helper virus if the transforming virus is
  defective
• Co-carcinogen, chemical, cigarette smoke

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Transformed cells

• lose contact inhibition
• continue to divide
• form random aggregations
• can become invasive
• Not warts Papovavirus

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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

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Human T-cell Leukemia Virus

• HTLV1 HTLV2
• retroviruses with no oncogenes
• Adult T-cell leukemia and lymphoma- Southern
  Japan, Carribean Islands, West Africa

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Epstein Barr

• Southern China, Asia
• suspect co-carcinogen- nitrosamines in salted
  fish
• oncogenes not reported.

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Burkitts Lymphoma

• East Africa, Papua New Guinea
• at risk 6 -14 year old males
• tumor of immature B-cells

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Human Papillomavirus

• cervical, penile, vulval, and rectal cancer
• viral genome integrated into host genome
• Co-carcinogens- cigarette smoke- HSV herpes

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Cytomegalovirus
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Cytomegalovirus

• Urine isolate

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Intranuclear inclusions

• The cell swells and a large inclusion body forms
  in the nucleus.

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Cytomegalovirus

• Nuclear cytoplasmic inclusions

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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.

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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.

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Disseminated cytomegalovirus

• fever, severe diarrhea, hepatitis, arthritis,
  pneumonia, high mortality.
• activation of inapparent infection.
• also due to
• immunosuppressive therapy.
• cancer.
• AIDS.

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Virus in blood or organ

• post transfusion.
• post organ transplant.

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Cytomegalovirus mononucleosis

• teenage, young adult similar to other mono.

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Transmission

• saliva, respiratory mucus, milk, urine, semen,
  cervical secretions, feces and lymphocytes.

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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.

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Laboratory diagnosis CMV

• virus can be grown from all organs.
• many serological tests.

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Treatment CMV

• gancyclovir, foscarnet, hyperimmune CMV
  immunoglobulin, have some effect.
• interferon does not prevent infection or promote
  recovery.

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PreventionCMV

• no animal can be found that can be infected with
  CMV.
• Two deterents
• vaccine stimulated antibodies may not be
  protective. Patients already seropositve can be
  reinfected.
• a vaccine could be oncogenic.

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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.