1. Viral infections of Reproductive system and Genital area: 1-Herpesviridae Family. 2-Papovaviridae Family. Herpesviridae: -Icosahedral, enveloped double stranded DNA viruses. -Three subfamilies: 1-Alpha-herpesviruses: HSV-1, HSV-2, VZV 2-Beta-herpesviruses: CMV, HHV-6, HHV-7 3-Gamma-herpesviruses: EBV, HHV-8

2. n Herpes simplex virus type-2 (HSV-2): -Icosahedral, enveloped double stranded DNA viruses. -Genome around 150 Kbp. -Homology by 50-70% with HVS-1; sharing epitopes. -Man is the only natural host. -Transmitted by Sexual contact or as a perinatal infection.

3. N Pathogenesis and clinical presentation of HSV-2: -Primary infection: (Herpes genitalis): - Painful bilateral vesiculo-ulcerative lesions: on the vulva, cervix and vagina or the penis with itching. -Extensive infection: fever and inguinal lymph node inf. -Latency: in Sacral ganglia. -Reactivation of Endogenous infection: 1-Takes place during sexual intercourse. 2-Seen at any site innervated by affected neurons. 3-It occurs due to immunosuppression.

4. N Other diseases caused HSV-2 infection: 1-Neonatal herpes: - The most serious consequence of genital herpes. - It is acquired during birth (Perinatal). 2-Aseptic meningitis. Genital Herpes Simplex in Males and Female:

5. n Laboratory diagnosis of HSV-2 Infection: 1-Direct detection: A-For viral antigen : Immunofluorescent Microscopy. or Electron Microscopy. B-For viral genetic material: by PCR. 2-Indirect diagnosis: Serology: Detection of anti-viral antibodies in patient’s serum. (IgM or IgG). 3-Tissue culture: Cellular ballooning cytopath-effect

6. n The Family Papovaviridae: The human papillomavirus (HPV): -It is a non-enveloped double stranded circular DNA Virus with Icosahedral capsid. -Epithelio-tropic virus. -It has seven early capsid proteins (E1 to E7), and two late structural proteins (L1 and L2). -Based on L1 gene sequence difference, there are over 100 types of HPV; 40 can cause anogenital infection.

7. n Pathogenesis of HPV: -Transmission: sexual contact. -Primary infection of basal cell layer of stratified squamous epithelium. -Some types produce chronic infection in which the viral genetic material is not-integrated with cell chromosome. -Others types cause high grade-dysplasia due to integration of viral genetic material within cell chromosome; Expression of E6, and E7 protein.

8. N -In high-risk HPV infection:(Oncogenic viruses): 1-E6 interacts with P53 and promotes its degradation. 2-E7 interacts with retinoblastoma protein (Rb) and inactivating it. -These are Tumor suppressor proteins that play a central role in DNA repair and control of cell division. -Cervical Malignant tumor.

9. n Human papillomaviruses cause four different genital tract abnormalities: 1-Anogenital Warts in Men and Women: caused by HPV-6 and HPV-11. 2-Low-grade cervical dysplasia: caused by oncogenic and non-oncogenic types. 3-High grade cervical dysplasia: caused by oncogenic types (pre-malignant). 4-Cervical cancer: oncogenic viruses: caused by HPV-16 and HPV-18.

10. N Genital Warts: - Skin growths in the anogenital area with cauliflower-like growths. - In women, genital warts can appear on the vulva, urethra, cervix, vagina, or anus. - In men, warts can appear on the penis, scrotum, or anus. -Genital and anal warts are very contagious.

11. n HPV Perianal Wart: HPV Penis’s Warts:

12. n Cancer of Genital tissue: -HPV-16,18 are linked to cervical cancer as well as cancers of the penis, anus and other genital cancers. -In women, pre-cancerous cells can be detected in the cervix by a Pap smear test. -A Pap test is an examination of a woman’s internal genital organs. -It is the only way to detect abnormal cells in the cervix that could potentially develop into cancer cell line later in life. -A girl should have her first Pap test within 3 years of becoming sexually active.

13. n Laboratory diagnosis of HPV infection in early stage: Specimen: Cervical swab or biopsy sample for others. 1-Direct detection of abnormal cells: A-Cytology Lab: Pap smear stains. B-Immunohistochemistry: Staining of cells in Pap smear by anti-E6 and E7 Antibodies. 2-Direct detection of viral genes by: PCR or DNA sequence methods for L1 genes.

14. Congenital viral infections: 1-Human Cytomegalovirus: -Classification: Beta-herpesviridae. -Double stranded DNA enveloped virus. -The name “cytomegalo-” account for the swollen state of virally infected cells. -Transmission: Transplacental, Breast milk, saliva, sexual, and blood transfusion.

15. n Pathogenesis of CMV: -Infection of different cells (epithelial cells, Blood phagocytes). -Latency in blood monocytes and tissue macrophage. -Reactivation in immuno-competent patients. -Active infection in fetus. Clinical features of CMV infection: 1-In fetus and neonates: “cytomegalic inclusion disease” Congenital CMV syndrome in 20% with microcephaly, mental retardation, hepatosplenomegaly and jaundice. Blindness and growth retardation.

16. n 2-In immunocompromised patients: Mainly AIDS Patients or others: Severe organ disease in eyes (retinitis), brain (encephalopathy), Gut (colitis), and lung (pneumonitis). Three-week-old infant with Congenital cytomegalovirus infection with Purpuric skin lesions and hepatosplenomegaly.

17. N Laboratory diagnosis of CMV infection: 1) Isolation of the virus from throat washings, urine, exudate on tissue culture. 2) Detection of viral DNA by PCR. 3) Detection of viral antigens in urine or saliva. 4) Sero-diagnosis: Detection of CMV specific IgM or rising titer of IgG by ELISA. 5) Tissue biopsy: stained for Inclusion bodies. Lung section showing Typical owl-eye inclusions.

18. n 2-Parvovirus B19 Infection: (Erythrovirus B19): -Classification: Parvoviridae Family. -It is a non-enveloped, icosahedral virus that contains a single-stranded linear DNA genome. -Transmission: Blood-borne, transfusion, Transplacental, or respiratory-airborne inf. -In pregnant women: It is associated with Hydrops fetalis; due to severe fetal anemia; could lead to miscarriage.(before week No. 20). -It infects Red blood cell precursors in the bone marrow. -No vaccine, No effective treatment. Pregnant women should avoid contact with infected Children.

19. n 3-Rubella virus infection: -Classification: Togavirus. -Enveloped single-stranded RNA virus. -Disease: Congenital Rubella Syndrome (CRS). -Transmission: Respiratory airborne in Children and adults, Transplacental for fetus. -It has teratogenic properties: infects fetus cells where it stops cellular development and destroy the cells. -Infection of fetus could result in: Cardiac, ophthalmic, cerebral defects: Cataracts, blindness, deafness or ductus arteriosus. Vaccination for Girls:( childhood).