1. Sexually Transmitted Viral Infections: The most common viral causes are: 1. Herpes simplex virus type 2 (HSV-2) 2. Human papillomavirus (HPV) 3. Human immunodeficiency virus (HIV) 4. Human cytomegalovirus (HCMV) 5. Hepatitis B virus (HBV) 6. Molluscum contagiosum virus (MCV)

2. Prevalence of Common Viral Diseases:

3. Herpesviridae Family: Icosahedral, enveloped double stranded DNA viruses. Genome consists of long and short fragments which may be orientated in either direction, giving a total of 4 isomers. Three subfamilies: Alphaherpesviruses: HSV-1, HSV-2, VZV Betaherpesviruses: CMV, HHV-6, HHV-7 Gammaherpesviruses: EBV, HHV-8 Set up latent or persistent infection following primary infection Reactivation are more likely to take place during periods of immunosuppression.

4. Herpes virus Particle HSV-2 virus particle Note that all herpesviruses have identical morphology and cannot be distinguished from each other under electron microscopy

5.  Herpes Simplex Virus Type 2 (HSV-2): Double stranded DNA enveloped virus with a genome of around 150 kb The genome of HSV-1 and HSV-2 share 50-70% homology. They also share several cross-reactive epitopes with each other. Man is the only natural host for HSV. Transmission of HSV-2 by: A. Sexual contact, or B. Infection during birth.

6. Pathogenesis: Primary infections commonly asymptomatic; Symptomatic cases sometimes severe, prolonged, systemic manifestations: - Fever - Malaise - Myalgia - Local pain - Itching - Painful vesiculoulcerative lesions: on the vulva, cervix and vagina or the penis. Latency of HSV-2 is in sacral ganglia Reactivation often asymptomatic. o Takes place during sexual intercourse. o Manifest at any site innervated by the affected neurons.

7. HSV-2 Diseases: 1) Herpes genitalis: - The classical presentation. - Extensive bilateral painful vesicular lesions in the genital area, accompanied with fever, dysuria and inguinal lymphadenopathy. 2) Neonatal herpes: - The most serious consequence of genital herpes, and - is acquired during birth. 3) Aseptic meningitis.

8. Genital Herpes Simplex in Males Genital Herpes Simplex in Females

9. Laboratory Diagnosis: Identification is very important to prevent neonatal infection and HSV encephalitis. 1- Isolation of virus on tissue culture 2- Detection of HSV in vesicle fluid by electron microscopy 3- Detection of viral DNA by PCR 4- Detection of viral antigen by direct immunofluroescence or ELIZA 5- Serological diagnosis to detect IgM antibodies that indicates recent infection or reactivation

10. Diagnosis of HSV-2: Cytopathic Effect of HSV in cell culture: Positive immunofluorescence test Note the ballooning of cells. for HSV antigen in epithelial cell.

11.  Human Cytomegalovirus (HCMV): Belong to the betaherpesvirus subfamily of herpesviruses The name “cytomegalo-” account for the swollen state of virus-infected cells. The infected cells are typically enlarged and multinucleated. Double stranded DNA enveloped virus The structure of the genome of CMV is similar to other herpesviruses, consisting of long and short segments which may be orientated in either direction, giving a total of 4 isomers. A large number of proteins are encoded for, the precise number is unknown.

12. Pathogenesis: Transmission: 1. Sexual intercourse. 2. Blood transfusion. 3. Organ transplantation. 4. Breast feeding. 5. Transplacental. Primary infection: usually asymptomatic In symptomatic cases, CMV replicates in epithelial cells of respiratory and gastrointestinal tracts viremia infection of all organs of the body. Latency: in monocytes and macrophages. Reactivation: common in immunocompromised persons.

13. Clinical Features: 1) Congenital infection: may result in “cytomegalic inclusion disease” leads to congenital abnormalities as: - Growth retardation.- Microcephaly. Hepatosplenomegaly- Thrombocytopenia Blindness 2) Postnatal infection: usually asymptomatic. However, in a minority of cases, the syndrome of infectious mononucleosis may develop which consists of fever, lymphadenopathy, and splenomegaly. 3) Infections of immunocompromised patients: such as transplant recipients and AIDS patients are prone to severe CMV disease such as pneumonitis, retinitis, colitis, and encephalopathy.

14. Three-week-old infant with congenital cytomegalovirus infection with purpuric skin lesions and hepatosplenomegaly. Congenital Cytomegalovirus Disease:

15. Laboratory Diagnosis: 1) Isolation of the virus from throat washings or urine on tissue culture. 2) Detection of viral DNA by PCR. 3) Detection of viral antigens in urine or saliva. 4) Serodiagnosis: Detection of CMV specific IgM or rising titre of IgG by ELIZA or latex agglutination assay. Lung section showing typical owl-eye inclusions

16.  Human Papillomavirus (HPV): Family: Papovaviridae. Non enveloped, icosahedral, epitheliotropic double stranded supercoiled DNA virus. It is estimated that 75% of the adult population will have at least one HPV infection during their lifetime. Has great tissue and cell specificity, infecting only surface epithelia of skin and mucous membranes. The genome is contained within a spherical protein capsid with 7 early proteins (E1 to E7), and 2 late structural proteins (L1 and L2).

17. Based on L1 gene sequence difference, there are over 100 types of HPV; 40 can cause anogenital infection. Low-risk HPV types: cause anogenital warts and other benign lesions High-risk HPV types: are associated with malignant carcinomas (mainly of the cervix).

18. Pathogenesis: Transmission: 1. Sexual contact. 2. Contaminated surfaces (fomites) 3. From mother to an infant during delivery (rare) How Does HPV “Cause” Cancer?  HPV produces a chronic infection of basal cell layer of stratified squamous epithelium.  HPV DNA persist non integrated in normal infected cells.  But integrated in host cell chromosome in high grade dysplasia cells high expression of E6 and E7 genes high expression of E6 and E7 proteins.

19. In high-risk HPV strains: E6 and E7 interact with many cellular proteins, which influence the outcome of infection. Protein E6 interacts with p53 in the host cell and promotes it’s degradation. Protein E7 complexes with retinioblastoma protein (Rb), thereby inactivating it. Rb and p53 are both tumor suppressors, involved in DNA repair and cell death. HPV Infection Outcomes

20. Clinical Picture: 1) Genital warts: - Skin growths in the anogenital area with cauliflower-like growths. - In women, genital warts can appear on the vulva, urethra, cervix, vagina, anus or thighs. - In men, warts can appear on the penis, scrotum, anus or thighs. - Genital and anal warts are very contagious. - Sometimes genital warts last for years and sometimes disappear without treatment.. - Genital and anal warts can sometimes come back.

21. HPV Perianal Wart: HPV Penile Warts:

22. 2) Cancer of the genital tissues: High risk types of the HPV virus are linked to cervical cancer as well as cancers of the penis, of the anus and other genital cancers. In women, pre-cancerous cells can be detected in the cervix by a Pap test. It is unlikely that a young girl will be diagnosed with cervical cancer as it takes many years for a cancer to develop. What is a Pap 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 later in life. A girl should have her first Pap test within 3 years of becoming sexually active.

23. Laboratory Diagnosis: 1. HPV cannot be cultivated to diagnose infections. 2. For cervical screening: Cervical swabs or biopsy samples are subjected to: a. Cytology (Pap smear) b. Detection of cervical biomarkers: include E6 and E7 c. Hybridization or PCR molecular assays: to detect HPV L1 DNA sequences, E6 or E7 mRNA