Epstein Barr Virus Herpes virus group Cytomegalovirus Herpes virus group Mumps VirusParamyxovirus group

Herpes Virus Structure  Icosahedral virus  Lipoprotein envelope, derived from the nuclear membrane  Genome: linear, ds DNA  Replicate in the nucleus

Herpes Virus Group  Includes: HSV-1, HSV-2, VZV CMVEBV CMV, EBV HHV-6 and others  Lytic and latent infections  Immortalizing effect (EBV)

EPSTEIN-BARR VIRUS

CD21)  EBV has a very limited host range and tissue tropism defined by the limited cellular expression of its receptor (CD21).  This receptor is expressed on B lymphocytes Epithelial cells of the oro – and nasopharynx

Diseases  Infectious Mononucleosis  African Burkitt’s Lymphoma  Nasopharyngeal Carcinoma  EBV-induced lymphoproliferative disease

EPIDEMIOLOGY  EBV is transmitted in saliva.  The immunosuppressive potential of malaria has been suggested as a cofactor in progression of latent EBV infection to African Burkitt’s lymphoma.  The restriction of nasopharyngeal carcinoma to certain regions of China has suggested a genetic predisposition.  Transplant patients, AIDS patients are at high risk for Lymphoproliferative disorders initiated by EBV.  B-lymphocytes transformation, by EBV does not need viral genome integration. (Episomal genome)

EBV in saliva Epithelial cells of oropharynx B cells proliferation T cells activation Liver Lymph node Spleen Shedding in saliva Pharyngitis Heterophile antibodies Atypical lymphocytes swelling

THE LATENT CYCLE EB nuclear antigen 1 ((EBNA-1 Viral promoter (ori P) EBNA-2 B cell immortalization Monoclonal antibodies (Heterophile antibodies) Antibodies to EBNA persist for life. Antibodies to viral capsid antigen (VCA)appear during active disease. CD8+ T cells are activated against EBNA proteins Destroy infected B cells Atypical lymphocytes T cell immunodeficiencies B cell lymphoma

Infectious Mononucleosis CLINICAL FEATURES Infectious Mononucleosis (IM)  Fever, malaise, pharyngitis, lymphadenopathy, hepatosplenomegaly.  The disease is rarely fatal.  Heterophile antibody positive.  The classical lymphocytosis associated with IM is due to activation and proliferation of suppressor (CD8+) T cells. These cells appear as atypical lymphocytes (Downey cells).

EBV-induced lymphoproliferative disease  Individuals lacking T-cell immunity are likely to suffer polyclonal leukemia-like B-cell proliferative disease and lymphoma upon EBV infection.  Transplant patients are at high risk for post-transplant lymphoproliferative disorder (PTLD).

African (endemic) Burkitt’s lymphoma  Poorly differentiated monoclonal B- cell lymphoma  jaw and face  endemic to children of malarial regions of Africa.  The tumor cells contain chromosomal translocations that moves the C-myc oncogene to a very active promoter. (Immunoglobulin gene promoter)

 Nasopharyngeal carcinoma The tumor is endemic to China The tumor is of epithelial origin.  Oral hairy leukeplakia Mouth lesions An opportunistic presentation in AIDS patients.

LABORATORY DIAGNOSIS  Atypical lymphocytes, lymphocytosis

 Heterophile Antibody (Paul-Bunnell or Monospot Test) (Paul-Bunnell or Monospot Test) IgM antibody that recognizes the Paul-Bunnell antigen on sheep and bovine erythrocytes but not guinea pig kidney cells. It is an excellent indication of EBV infection in adults, not children.  Other Serological Tests IgM antibody to VCA, most specific test.  Treatment No vaccine available. Acyclovir is used in treating oral hairy leukoplakia.

CYTOMEGALOVIRUS

DISEASES  Cytomegalic inclusion disease  Heterophile negative mononucleosis  Diseases in the immunocompromised patients

PROPERTIES  Icosahedral virus  Lipoprotein envelope, derived from the nuclear membrane  Genome: linear, ds DNA  Replicate in the nucleus  Latent infections  Single serotype  Humans are the natural hosts  Giant cell formation (Cytomegalo)

TRANSMISSION  Oral (saliva) and respiratory routes  Transplacental, within the birth canal and in breast milk  Sexual (semen, cervical secretions)  Blood transfusion and organ transplantation  More the 80% of adults have antibody against this virus.

CLINICAL FORMS  Normal host Asymptomatic latent infection Infectious mononucleosis-like syndrome (Heterophile antibodies- negative).  Immunocompromized host (AIDS patients, those receiving organ transplants or chemotherapy) Pneumonia, hepatitis Severe diarrhea and retinitis in AIDS patients  Congenital infection in utero: Infection of the fetus occurs when a primary infection happens in a pregnant woman (no virus neutralizing antibodies) Abortion Stillbirth

Cytomegalic inclusion disease  Congenital abnormalities are more common when the fetus is infected during the first trimester of pregnancy.  Includes microcephaly, mental retardation, blindness or deafness.  Hepatosplenomegaly is very common.

LABORATORY DIAGNOSIS  Cell culture with the use of immunofluorescent antibody.  PCR-based assays. intranuclear and an oval “owl’s-eye” shape  Histological staining of inclusion bodies in giant cells: intranuclear and an oval “owl’s-eye” shape.  Rising IgG antibody titre or single IgM antibody test

TREATMENT  Ganciclovir is effective in the treatment of CMV retinitis and pneumonia in AIDS patients.  Fomiversin is antisense DNA approved for the intraocular treatment of CMV retinitis. It is the first antisense molecule to be approved for the treatment of human disease.

MUMPS VIRUS

 VIRUS Paramyxovirus ssRNA, non- segmented genome Single serotype  TRANSMISSION Humans are the natural host Respiratory droplets Peak incidence in winter

PATHOGENESIS  URT Blood Parotid glands, testes, pancreas and meninges  Lifelong immunity occurs

CLINICAL PICTURE  Incubation period: days  Prodrome: fever, malaise and anorexia  Parotid gland swelling  Resolve spontaneously within 1 week  Complications  Orchitis bilateral sterility  Meningitis

 LABORATORY DIAGNOSIS  Virus isolation from saliva, spinal fluid  Rising antibody titre  PREVENTION  Live attenuated vaccine  MMR (Measles, Mumps, Rubella)