Epstein Barr Virus

STRUCTURE & GENOME:
  • The virus is approximately 122-180 nm in diameter and is composed of a double helix of DNA.
  • The DNA is surrounded by a protein nucleocapsid.
  • This nucleocapsid is surrounded by a tegument made of protein, which in turn is surrounded by an envelope containing both lipids and surface projections of glycoproteins which are essential to infection of the host cell.
  • Epstein-Barr virus (EBV) is a human γ-herpesvirus that is able to establish a long-term, latent infection in human B cells for the life of the host

 DISEASE ASSOCIATION:
  • Infectious Mononucleosis
  • Burkitt's lymphoma
  • Nasopharyngeal carcinoma
  • Lymphoproliferative disease and CNS lymphoma in the immunosuppressed.
  • X-linked lymphoproliferative syndrome
  • Malignancies caused by EBV includes Burkitt’s lymphoma, Hodgkins disease, Post transplant lymphoma, Tcell lymphoma, Nasopharyngeal carcinoma, Gastric carcinoma and Leiomyosarcoma.
  • Oral leukoplakia in AIDS patients
  • G.B syndrome
  • Transverse myelitis
  • Glandular fever
  • Chronic interstitial pneumonitiswith pleural effusion in AIDS patients.
MOLECULAR BIOLOGY:
  • To infect cells, EBV uses a cell surface receptor (CR2,CD21) found primarily on B lymphocytes and nasopharyngeal epithelial cells.
  • Epstein Barr virus causes autoimmunity by Polyclonal B cell Activation
  • MHC class II protein functions as a cofactor for this virus-receptor interaction.
  • After infection of epithelial cells, active replication occurs and leads to lysis and death of the cell.
  • Viral capsid antigens (VCAs) are the primary structure proteins in viral capsids and are found in replicating cells.
  • EBV early antigens (EAs) consist of >15 proteins codes by genes distributed throughout the genome.
  • EBV nuclear antigen (EBNA) corresponds to six virally encoded proteins found in the nucleus of an EBV-infected cell.
  • Latently infected B cells are the primary reservoir of EBV in the body.
  • >100 gene products may be expressed during active viral replication, only 11 are expressed during viral latency.
  • In this way, the virus limits cytotoxic T-cell recognition of EBV-infected cells.
DIAGNOSIS:
  • The clinical diagnosis can be made from the characteristic triad of fever, pharyngitis, and lymphadenopathy lasting for 1 to 4 weeks.
  • Hematologic complications, including hemolytic anemia, thrombocytopenia, and neutropenia, are more common.
  • Neurologic involvement can include aseptic meningitis, lymphocytosis, encephalitis, isolated neuropathy such as Bell palsy, and Guillain-Barré syndrome.
  • Acute EBV infection is usually made by the heterophil antibody test and/or detection of anti-EBV VCA IgM.
  • Cases of Burkitt’s lymphoma should be diagnosed by histology. The tumour can be stained with antibodies to lambda light chains which should reveal a monoclonal tumour of B-cell origin. In over 90% of cases, the cells express IgM at the cell surface.
  • Cases of NPC should be diagnosed by histology.
  1. The determination of the titre of anti-EBV VCA IgA in screening for early lesions of NPC and also for monitoring treatment.
  2. A patient with with non-specific ENT symptoms who have elevated titers of EBV IgA should be given a thorough examination.
PAUL BUNNELL TEST
  1. The original Paul-Bunnell test was a simple titration of sheep cell agglutinins but this procedure was subsequently modified in order to distinguish between sheep cell agglutinins formed in IM and the Forssmann-type antibodies found in normal serum, serum sickness and in certain other conditions.
  2. Tissues rich in Forssmann antigen (guinea pig kidney) absorb Forssmann antibodies but do not affect the heterophile antibodies in IM.
  3. Heterophile antibodies are absorbed by beef cells,
  4. Forssmann Hapten is a glycolipid usually associated with a protein, the determinant being largely carbohydrate and therefore heat stable.
DAVIDSOHN DIFFERENTIAL:
  1. Patients serum containing antibodies due to IM is added to guinea pig kidney cells. 
  2. These antibodies are not absorbed by the kidney cells. These antibodies then react with Beef (Ox) red blood cells which causes agglutination and is a positive test for IM.
  3. Patients serum containing Forssmann antibodies are added to guinea pig kidney cells. Antibodies are absorbed by the kidney cells. 
  4. These antibodies are then allowed to react with Beef red blood cells which does not cause agglutination.
  5. This is a positive test for Forssmann antigens.
Exam Question
  • Paul Bunnel test is done for EBV
  • Oral hairy leukoplakia is associated with EBV
  • Burkitt's lymphoma is caused by EBV
  • Malignancies caused by EBV includes Burkitt’s lymphoma, Hodgkins disease, Post transplant lymphoma, Tcell lymphoma, Nasopharyngeal carcinoma, Gastric carcinoma and Leiomyosarcoma.
  • Nasopharyngeal carcinoma is caused by EBV
  • Infectious Mononucleosis is caused by EBV
  • Lymphoid tissue is the site of latent infection for EBV
  • Neurologic involvement can include aseptic meningitis, encephalitis, isolated neuropathy such as Bell palsy, and Guillain-Barré syndrome.
  • Lymphoepethelioma of the parotid gland is associated with EBV
  • Epstein Barr virus causes autoimmunity by Polyclonal B cell Activation
  • Lymphocytosis with atypical lymphocytes are seen in infection with EBV
  • Pneumonia with pleural effusion can be caused by EBV
  • EBV is a DNA oncogenic viruses
  • Lymphoproliferative disease in the immunosuppressed is caused by EBV
  • CNS lymphoma in the immunosuppressed is caused by EBV
  • Glandular fever is caused by EBV
  • EBV receptor located on surface of B cells is CD21

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