1. EBV,CMV& MUMPS V By: Dr.Malak El-Hazmi Assistant Professor & Consultant Virologist College of Medicine & KKUH

2. Herpesviridae 1-Herpes simplex type -1 HSV-1 1-Herpes simplex virus type -1 HSV-1 2-Herpes simplex virus type -2 HSV-2 3-Varicella –Zoster virus VZV 4-Epstein- Barr virus EBV 5-Cytomegalovirus CMV 6-Human herpes virus type-6 HHV-6 7-Human herpes virus type-7 HHV-7 8-Human herpes virus type-8 HHV-8

3. HERPESVIRUS dsDNA, Enveloped, Icosahedral Virus

4.   Features of herpesviruses   All herpesviruses are structurally identical   Replicate in nucleus Intranuclear inclusions Envelope from nuclear mb   Latent infection   Cause high morbidity and mortality in immuno ed patients   Some herpesviruses   Associated with cancers e.g. EBV & HHV8 Herpesviridae

5. Subfamily Virus Target cell Latency Subfamily Virus Target cell Latency Alpha HHV1 HHV2 HHV3 HSV1 HSV2 VZV Mucoepithelial Neuron Beta HHV5 CMV Monocyte Lymphocyte& Epithelial cells Mono & lymphocyte Gamma HHV4 EBV B lymphocyte, Epithelial cells B lymphocyte Classification of human herpesviruses

6.   HHV-4, gammaherpesvirinae   Special features   It is lymphotropic   Its antigenic composition   It has oncogenic properties Epstein – Barr Virus EBV  Nuclear antigens [EBNAs]  Early antigen [EA]  Viral capsid antigen [VCA] Immortalize the host cells Infected B cells a lymphoid cells line transformation proliferate

7.   Distribution :worldwide   Transmission:   Saliva [kissing disease]   Blood [rarely]   Age: Socio-economic status: SE   Low SE class early childhood   High SE class adolescence Epidemiology EBV

8. Pathogenesis:  EBV in saliva pharyngitis pharyngitis  Epithelial cells of oropharynx shedding in saliva  B-cell proliferationHeterophile antibodies  T-cell activation Atypical lymphocytes  Liver, spleen & lymph node swelling EBV

9. Immunity:   Humoral I:   VCA IgM current inf.   VCA IgG past inf.   Antibodies to the viral mb ag immune   CMI:   T-cells control disease   CMI B-cell lymphoproliferative disease.  Latent reactivation V shedding EBV

10.   Asymptomatic   Infectious mononucleosis [glandular fever]   Mainly in teenagers & young adults   IP = 4-7 weeks   Fever, pharyngitis, malaise, LAP, hepatosplenomegaly & +/- hepatitis   Rash may follow ampicillin   Last 2- 3 weeks   Complications ( acute air way obstruction, splenic rupture, CNS inf )   Chronic EBV inf Clinical Features: Immunocompetent host Immunocompetent host EBV

11.   Lymphoproliferative disease ( LD)   CMI patients LD & lymphoma   Transplant recipients PTLD   Oral hairy leukoplakia (OHL)   Non-malignant lesion   HIV-infected patients immuno ed patients Clinical Features : Immunocompromised host Immunocompromised host EBV

12. EBV –Associated Malignancies   Burkitt’s lymphoma   A tumor of lymphoid tissue   African children   Pathogenesis   environmental factors [ malaria can act as a cofactor]   genetic alternation [ C-myc oncogene 8 to 14 ]

13. EBV –Associated Malignancies  Nasopharyngeal carcinoma   Epithelial origin   Adult   China

14.   Hematology:   WBC lymphocytosis Atypical lymphocytes Diagnosis: EBV

15. Diagnosis   Serology:   Non-specific AB test: Heterophile Abs +ve Paul-Bunnell or monospot test   EBV specific AB test: IF or ELISA EBVCA-IgM   EBV Ags & EBV-DNA in lymphoid tissue EBV

16. Serological Profile for EBV Infections Pts clinical status HA EBV-specific antibodies VCA-IgM VCA-IgG EA-AB EBNA -AB Susceptible Acute Chronic 1 o Past inf. Reactivation inf BL NPC -- -- + +± - - + + - - + - - + - - + + + + + + + + + - + - - - - -

17.   Treatment:   Antiviral drug is not effective in IM   Acyclovir is used in treating OHL   Prevention:   No vaccine Management: EBV

18.   Betaherpesvirinae – HHV-5   Special features   Its replication cycle is longer   Infected cell enlarged [cyto=cell, megalo=big]   Resistant to acyclovir   Latent in monocyte & lymphocyte & other Cytomegalovirus CMV

19.   Distribution: worldwide   Transmission   Early in life:   Transplacenta   Birth canal   Breast milk   Young children: saliva   Later in life: sexual contact   Blood transfusion & organ transplant Epidemiology CMV

20.   Immunocompetent host   Asymptomatic   Self-limited illness   Hepatitis   Infectious mononucleosis like syndrome [Heterophile AB is –ve]   Immunocompromised host   1 o or R   Pneumonia, Hepatitis, Encephalitis   Retinitis, Esophagitis, Colitis Acquired Infection CMV

21. Congenital Infections: Clinically normal 15% Hearing defect mental retardation 4% Cytomegalic inclusion disease 1% death CMV

22. Expanded Generalized Defects CIDRubella herpes syndrome simplex Low birth wt. Hepatosplenomegaly Thrombocytopenia Skin vesicles Microcephaly Meningitis, encephalitis Intracranial calcification Retinitis Cataracts Heart Lesions Bone defects Deafness, speech defect,MR ++ + + + ++ + ++ + + + + + + + + + CMV Congenital Infections:

23. Lab. Diagnosis Histology : Intranuclear inclusion bodies [Owl’s -eye] CMV

24. Lab. Diagnosis Culture: Culture:  In human fibroblast  1-4 wks CPE  Shell Vial Assay 1-3 days 1-3 days Serology: Serology:  AB IgM: 1 or R inf. IgG: previous exposure  Ag CMV pp65 Ag by IFA PCR PCR CMV

25. Treatment Ganciclovir is effective in the Rx of severe CMV inf. is effective in the Rx of severe CMV inf. e.g. CMV retinitis, pneumonia Foscarnet : the 2nd drug of choice CMV

26. Prevention:  Screening organ donorsorgan donors Organ recipientsOrgan recipients Blood donorsBlood donors  Leukocyte-depleted blood  Chemoprophylaxis: Ganciclovir  Immunoprophylaxis: CMVIG  No vaccine CMV

27. Mumps Virus   Family: Paramyxoviridae   Structure:   ssRNA   Helical nucleocapsid   Envelope with 2 spikes   H + N   Fusion (F)   Single serotype

28. Epidemiology Distribution: Worldwide Age < 15 years Transmission:   Saliva   Respiratory droplet Peak incidence in winter mumps

29.   Virus URT Parotid glandImmunity Life-long immunity Stensen’s Duct Testes, ovaries, pancreas,thyroid,meninges …… Viremia Pathogenesis: mumps

31. Clinical Features:   IP = 18-21 days   Prodrome ; fever, malaise, anorexia   Painful swelling of parotid glands   Duration 1 wk.   Complications   Orchitisbilateral sterility   Meningitis, Post infectious encephalitis mumps

32. Lab. Diagnosis   Cell culture:   Throat swabs, CSF, blood, urine   CPE haemadsorption IFA staining   Serology:   IgM mumps

33. Treatment;   not specific Prevention;   LAV, MMR   SlC, IM   12-15 ms & 4 to 6 yrs   Effective Management mumps

34. عن  عائشه  رضي  الله  عنها،  عن  النبي  صلى  الله  عليه  وسلم  ،  قال    ركعتا  الفجر  خير  من  الدنيا  ومافيها 