EB VIRUSES

Epstein-Barr Virus (EBV)

• Spread through oral transmission (SALIVA)

• Infectious Mononucleosis.

• Other Diseases include:– African or Burkitt’s lymphoma– Nasopharyngeal carcinoma– B cell lymphoma

Viral Antigens

• There are three classes :-

1.Latent phase(EBNAs & LMP)

2.Early phase(proteins)

3.late phase

Epstein-Barr virus

• African or Burkitt’s Lymphoma– malignant B-cell neoplasm – presents as a rapidly growing tumour of

the jaw, face or eye– grows very quickly, and without treatment

most children die within a few months – Epstein-Barr virus (EBV) has been

strongly implicated

African or Burkitt’s Lymphoma

• Although BL is a very rapidly growing tumour it responds well to treatment.

• Three pictures: before treatment, 3 days and 6 days after treatment

Nasopharyngeal Carcinoma

• Endemic in South China, Africa, Arctic Eskimos

• This is a malignant tumour of the squamous epithelium of the nasopharynx.

• 100% contain EBV DNA• Rates are less than 1 per 100,000 in most

populations • Nasopharyngeal carcinomas are found in

association with reactivation of latent Epstein-Barr Virus. 

• The exact mechanisms of association are unknown

B-Cell Lymphoma

• In most individuals infected with EBV, the virus is present in the B-cells, which are normally controlled by T-lymphocytes

• When T-cell deficiency exists, one clone of EBV-infected B-lymphocytes escapes immune surveillance to become autonomously proliferating.

• EBV induced B cell lymphomas are most prevalent in immunocompromised patients.

Oral Hairy Cell Leukoplakia

• Viral infection of the oral cavity. • Indicator of HIV infection as well as of a

person's lessening or weakening immunity

Infectious Mononucleosis

• 4 to 7 week incubation• Acute self-limiting infection of the RE system• Enlarged lymph nodes in the neck.• Sore throat, fever, rash• Malaise, lethargy, extreme tiredness• Liver and spleen involvement and

enlargement• Hematology: High WBC, over 20% atypical

reactive lymphocytes also known as Downey cells.

Infectious Mononucleosis

• Downey cells may be present

Heterophile Antigens/Antibodies

• Heterophile antigens are a group of similar antigens found in unrelated animals, IE, man, sheep, horse, dog cat, mouse.

• Heterophile antibodies produced against heterophile antigens of one species will cross react with others.

Heterophile Antigens/Antibodies

• Forssman antigen is an example of a heterophile antigen and is found on the RBCs of many species (guinea pig, dog, cat, mouse, sheep, fowl, horse)

• Forssman antibodies formed against Forssman antigens will agglutinate sheep RBCs.

Paul Bunnell Test

• 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 Forssman-type antibodies found in normal serum, serum sickness and in certain other conditions.

• Tissues rich in Forssman antigen (guinea pig kidney) absorb Forssman antibodies but do not affect the heterophil antibodies in IM.

• Heterophil antibodies are absorbed by beef cells,• Forssman hapten is a glycolipid usually associated with a

protein, the determinant being largely carbohydrate and therefore heat stable.

Davidsohn Differential

• The principle behind the Paul-Bunnell-Davidsohn test is that the two types of sheep agglutinins are distinguished by titrating them before and after absorption with guinea pig kidney and ox cells.

• Patients serum containing antibodies due to IM is added to guinea pig kidney cells. 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.

• Patients serum containing Forssman antibodies are added to guinea pig kidney cells. Antibodies are absorbed by the kidney cells. These antibodies are then allowed to react with Beef red blood cells which does not cause agglutination. This is a positive test for Forssman antigens.

Davidsohn Differential* To be considered absorbed there must be greater than a three tube difference between the presumptive titer and the differential titer.

Heterophil Antibody

------------------------ Infectious Mono

Kidney Extract ------------------ Not Absorbed

Beef Erythrocyte --------------------- Absorbed

Forssman

Absorbed

Not Absorbed

Serum Sickness

Absorbed

Absorbed

Davidsohn Differential

Advantages

• When properly performed, this test is specific for Infectious Mononucleosis and false-positive results are rare.

Disadvantages

• Davidsohn Differential test is very time consuming and burdensome.

Infectious Mono Slide Tests

• It was discovered that horse RBCs possess antigens which react with the antibody associated with IM.

• Patient serum mixed with horse RBCs, agglutination is positive.

• Latex agglutination

• Not diagnostic, must look at total clinical picture.

EBV Specific Antibodies

• EBV specific antibodies may be measured.• Pattern of appearance of EBV antigens.• Most valuable is IgM antibody to viral capsid

antigen (VCA), indicates a current infection (best marker), lasts about 12 weeks.

• Can also detect anti-early antigen (EA) (recent infection) and anti EB nuclear antigen (EBNA) (older infection).

• ELISA and IFA most commonly used