Human Herpes Virus.pptx

A type of virus that causes herpes infections and has DNA as its genetic material. There are two types of human herpesviruses. Infections with type 1 viruses cause cold sores on the lips or nostrils. Infections with type 2 viruses cause sores on the genitals (external and internal sex organs and glands).

1. Human Herpes Virus (HHVs)

2. Introduction It’s a kind of enveloped DNA virus. Icosahedral core surrounded by a lipoprotein envelope. linear double-stranded DNA. Large (120 – 200 nm in diameter), second in size only to poxviruses. Capsid surrounds DNA core and over the capsid is tegument (a protein-filled region). Nuclear membrane derived lipid bilayer containing viral glycoproteins

3. H S V - 1 HS V - 2 VZV EBV CMV HH V - 6 HH V - 7 HH V - 8 The Herpes virus family includes 8 different enveloped DNA-containing viruses that only affect human beings.

4. Subfamily Duration of replication and Cytopathology Site of latency Species Official name Common name Alpha Short, Cytolytic Neurons HHV 1 Herpes simplex virus 1 HHV 2 Herpes simplex virus 2 HHV 3 Vericella -zoster virus Beta Long, Cytomegalic Glands, kidney HHV 5 Cytomegalovirus Long, lymphoproliferative Lymphoid tissues (T cells) HHV 6 HHV 7 Human herpes virus 6 Human herpes virus 7 Gamma Variable, lymphoproliferative Lymphoid tissues (B cells) HHV 4 Epstein-Barr virus HHV 8 Kaposi’s sarcoma associated herpes virus

5. Herpes simplex virus T ype 1 (HSV-1) and T ype 2 (HSV-2) are distinguished by two main criteria Antigenicity location of lesions. HSV-1: above the waist, primarily in adults Acute gingivostomatitis, Recurrent herpes labialis (cold sores), Keratoconjunctivitis (keratitis), Encephalitis HSV-2: below the waist herpes genitalis(genital herpes), Neonatal encephalitis and other forms of neonatal herpes Aseptic meningitis Humans are the natural hosts of both. Herpes simplex virus

6. DNA released in the cytoplasm DNA migrates to the nucleus mRNA (transcription) synthesis takes place in the nucleus by using host RNA polymerase mRNA transported to the cytoplasm New viral proteins made and migrate to nucleus Genomic DNA (replication) synthesis takes place in the nucleus by using viral DNA polymerase Hsv replication

7. HSV 1: transmitted primarily in saliva. HSV 2: transmitted by sexual contact Oral–genital sexual activity: HSV-1 infections of the genitals and HSV-2 lesions in the oral cavity. – 10 – 20% of cases Hsv transmission

8. causes several forms of primary and recurrent disease. Gingivostomatitis Occurs primarily in children and is characterized by fever, irritability, and vesicular lesions in the mouth. The primary disease is more severe and lasts longer than recurrences. The lesions heal spontaneously in 2 to 3 weeks. Many children have asymptomatic primary infections Herpes labialis fever blisters or cold sores is the milder, recurrent form characterized by vesicles , usually at the mucocutaneous junction of the lips or nose Recurrences frequently reappear at the same site. Clinical findings of HSV1

9. Keratoconjunctivitis characterized by corneal ulcers and lesions of the conjunctival epithelium. Recurrences can lead to scarring and blindness Encephalitis necrotic lesion in one temporal lobe. Fever, headache, vomiting, seizures, and altered mental status Clinical findings of HSV1

10. Herpetic whitlow pustular lesion of the skin of the finger or hand. It can occur in medical personnel as a result of contact with patient’s lesions. Herpes gladiatorum wrestlers and others who have close body contact. vesicular lesions on the head, neck, and trunk. Disseminated infections, such as esophagitis and pneumonia, occur in immunocompromised patients with depressed T-cell function. Clinical findings of HSV1

11. Genital herpes painful vesicular lesions of the male and female genitals and anal area The lesions are more severe and protracted in primary disease than in recurrences. Primary infections are associated with fever and inguinal adenopathy . Clinical findings of HSV2

12. Neonatal herpes originates chiefly from contact with vesicular lesions within the birth canal. varies from severe disease (e.g., disseminated lesions or encephalitis) to milder local lesions (skin, eye, mouth) to asymptomatic infection. prevented by performing cesarean section on women with either active lesions or positive viral cultures . Clinical findings of HSV2

13. Both HSV-1 and HSV-2 infections are associated with E.M. central red area surrounded by a ring of normal skin outside of which is a red ring “target” or “bull’s eye” lesion. lesions are typically macular or papular occur symmetrically on the trunk, hands, and feet Many drugs, especially sulfonamides among the antimicrobial drugs, commonly cause erythema multiforme. Other associated MCO: Mycoplasma pneumoniae and viruses such as hepatitis B virus and hepatitis C virus. Erythema multiforme major, also known as StevensJohnson syndrome Fever, erosive oral lesions, Extensive desquamating skin lesions. Erythema multiforme

14. Specimens :- Vesicle fluid, skin swab, saliva, corneal scrapings, brain biopsy and CSF Microscopy: - Toluidine blue stained smear- Multinucleated giant cells with faceted nuclei and homogeneously stained ‘ground glass’ chromatin ( Tzanck cells). Giemsa stained smear- Cowdry type A intranuclear inclusion bodies. Laboratory diagnosis A Tzanck smear : multinucleated giant cells

15. Cytopathic Effect of HSV in cell culture: Note the ballooning of cells. (Linda Stannard, University of Cape Town, S.A.) Positive immunofluorescence test for HSV antigen in epithelial cell. (Virology Laboratory, New-Yale Haven Hospital)

16. Electron microscopy- Virus particles demonstrated Immunofluorescent staining- Virus antigen demonstrated Tissue culture and Isolation:- Cell lines- Human fibroblasts, Hep-2 cells, vero cells and chorioallantoic membrane. Typical cytopathic changes (swollen, rounded cells) appear in 1-5 days .

17. Serology:- Useful in the diagnosis of primary infection. Detection of virus specific IgM antibody or rising titre of antibody by ELISA, CFT, RIA, neutralisation and immunofluorescence . Polymerase Chain Reaction (PCR):- DNA detection

18. Acyclovir : treatment of choice shortens the duration of the lesions reduces the extent of shedding of the virus Penciclovir (a derivative of acyclovir) Valacyclovir and famciclovir : G enital herpes and in the suppression of recurrences. treatment

19. avoiding contact with the vesicular lesion or ulcer. Cesarean section is recommended for women who are at term and who have genital lesions or positive viral cultures. prevention

20. Clinical chicken pox (primary infection) 90 % of cases before age 10, peak incidence 2- 8 years Virus entry through inhalation Replicates in respiratory tract and invades lymph nodes. Viremia : spreads virus to target organs Incubation period 14-18 days Vericella zoaster virus

21. Varicella Zoster Varicella (chicken Pox) and Herpes zoster are different manifestation of the same virus infection. Chicken pox follows infection in non immune patients, while herpes zoster occur in those patient who had chicken pox but now have low immunity –reactivation of latent virus (chicken pox caught but zoster reactivated)

22. Rash appears first on head, neck, trunk Vesicles contain clear fluid (itch) New vesicles appear during first week Mild fever, malaise, headache Recovery in 2 weeks Adult infections more severe (pneumonia) Neonatal infection (encephalitis ) Immunosuppressed (severe progressive infection) Vericella zoaster virus (chicken pox)

23. Shingles: reactivation of varicella-zoster DNA remains latent in ganglia Occurrence increases with age (50% over 50 yrs) Onset of pain occurs before appearance of vesicles Usually unilateral Immunosuppressed patients especially vulnerable Vericella zoaster virus (shingles)

24. Vzv ( superinfection )

25. Laboratory Diagnosis Diagnosis is usually clinical. Specimens:- Scrapings or fluid of vesicles Microscopy:- Multinucleated giant cells and type A intranuclear inclusion bodies are seen in smears stained with toluidine blue, Giemsa or Papanicolou stain. Electron microscopy- Virus particles demonstrated Immunofluorescent staining- Virus antigen demonstrated Culture and Isolation:- Cell lines- Human amnion, human fibroblast, HeLa or Vero cells.

26. Cytopathic Effect of VZV in cell culture: Note the ballooning of cells. (Coutesy of Linda Stannard, University of Cape Town, S.A.) Cytopathic Effect of VZV

27. Prevention immun o globulin for patients at risk Vaccine: live vaccine (VARIVAX, Merck & Co.) Recommended dose For susceptible children aged 12 months to 12 years is one 0.5 ml dose subcutaneously For susceptible adolescents aged 13 years and adults is two 0.5 ml doses 4 to 8 weeks apart

28. CYTOMEGALOVIRUS

29. Largest (150-200 nm) virus in the herpesvirus family. Also called salivary gland viruses of humans and animals Leads to prolonged latency in infected host. Most common cause of congenital defect . Transmitted through birth canal, saliva, breast milk, blood products and sexual exchange of body fluids. An individual infected with virus carries it for life. CYTOMEGALOVIRUS

30. CLINICAL SYNDROMES Congenital CMV infection Acquired CMV infection Perinatal CMV infection CMV mononucleosis Transfusion –acquired infection Infection in immunocomprised Infection in immunocompetent

31. CONGENITAL CMV INFECTION Transmission from mother to child through placental blood or ascending from cervix. Congenital infection can be asymptomatic or symptomatic Asymptomatic child normal can develop mental retardation and neurological defects Symptomatic disease acquired during pregnancy Microcephaly , hepatosplenomegaly , jaundice, mental retardation and hearing loss

32. Perinatal occurs through infected birth canal or breast milk child develop lymphadenpathy , hepatitis and pneumonitis CMV Mononucleosis disease of young adult aquired from person to person , blood transfusion patient. ACQIRED CMV INFECTION CMV in immunocompromised opportunistic infection pneumonitis, hepatitis, encephalitis, retinitis and many other symptoms CMV in immunocompetent Produces mononucleosis type symptoms Infection transmitted by sexual and oral contact

33. CMV - Infections

34. CMV affecting retina

35. Laboratory Diagnosis Specimens:- Urine, saliva, other body fluids Microscopy:- Demonstration of cytomegalic cells- Enlarged cells with large intranuclear “ owl’s eye” appearance inclusions. Culture and Isolation:- Grown in human fibroblast culture. Cytopathic effects take 2-3 weeks to appear (due to slow replication). Serology:- CMV specific IgM can be detected in the serum by ELISA.

36. EPSTEIN-BARR VIRUS (EBV) A ubiquitous herpesvirus . EBV infection occurs in infancy and childhood in developing countries and in adolescence in developed countries. Infection leads to latency, periodic reactivation and lifelong persistence. Sources of infection- Saliva of infected persons Mode of transmission- Intimate oral contact, as in kissing (Kissing disease).

37. Epstein Barr virus (EBV)-associated diseases Infectious Mononucleosis Burkitt lymphoma Nasopharyngeal carcinoma Lymphoproliferative Disease Hodgkin’s Disease, EBV-assoc. NHL Gastric carcinoma

38. Infectious Mononucleosis (Glandular Fever) An acute self-limiting illness usually seen in non-immune young adults. IP:- 4-8 weeks Characterized by fever, sore throat, lymphadenopahy and the presence of abnormal lymphocytes in peripheral blood smears. A mild transient rash may be present. In most cases, spontaneous resolution of the disease occurs in 2-4 weeks. Leads to mental and physical fatigue in convalescence.

39. IM – Clinical presentation

40. Laboratory Diagnosis Specimen:- Blood, Saliva, Lymphoid tissue White Blood Cell Count:- Leucopenia, in initial phase but later there is leucocytosis . Appearance of abnormal or atypical mononuclear cells

41. Paul- Bunnel Test During infectious mononucleosis, heterophile antibodies agglutinate sheep erythrocytes. Procedure:- Inactivated serum (56°c/ 30 min.) in doubling dilutions is mixed with equal volumes of a 1% suspension of sheep erythrocytes. Incubate at 37°c for 1hour Examine for agglutination. Result:- An agglutination titre of 100 or above is suggestive of infectious mononucleosis. +ve -ve

42. Other serological tests:- Immunofluorescence or ELISA

43. HUMAN HERPES VIRUS 6 & 7(HHV 6 AND HHV 7) First isolated in 1986. They are transmitted mainly through contact with saliva and through breast feeding. >90% of the world population by age 2 are HHV-6 and 7 positive. Like other herpesviruses , HHV-6 and HHV-7 remains latent in the body after primary infection and reactivates from time to time. Infects CD4+ T-cells

44. CLINICAL MANIFESTATIONS Primary HHV-6 infection is associated with Roseala Infantum , which is a classical disease of childhood. . A spiking fever develops over a period of 2 days followed by a mild rash. The fever is high enough to cause febrile convulsions. There are reports that the disease may be complicated by encephalitis.

45. If primary infection is delayed until adulthood, there is a small chance that an infectious mononucleosis-like disease may develop in a similar manner to EBV and CMV. There is no firm evidence linking HHV-6 to lymphomas or lymphoproliferative diseases. There is no firm disease association with HHV-7 at present.

46. HUMAN HERPESVIRUS 8 (HHV 8) First detected in 1994. Also called as Kaposi’s sarcoma associated herpes virus (KSHV) Transmitted through- Exchange of body fluids, sexual contact, organ transplantation, saliva (inefficient) Associated Kaposi’s Sarcoma Multicentric Castleman’s Disease ( lymphoproliferative disorder of B cells) body cavity based Lymphoma.

47. Kaposi’s sarcoma Classic Kaposi's sarcoma (CKS) is a neoplasm characterized by purplish, reddish blue, or dark brown/black macules , plaques, and nodules on the skin. mucous membranes of mouth and gastrointestinal (GI) tract and regional lymph nodes may be affected later in the course. Biopsy for definitive diagnosis radiation therapy, excision, cryotherapy , chemotherapy emedicine.medscape.com/article/279734-overview

48. A 7 years old boy developed multiple painful vesicle over the lips and buccal mucosa. His parents revealed that two children of of his school had similar presentation few days back. Scraping taken from the lesions demonstrated the presence of multinucleated giant cells ( Tzanck cells). What is the probable diagnosis? How is the infection diagnosed in the laboratory?

49. A neonate has hepatosplenomegaly . His urine was stained with Giemsa stain which revealed owl’s eye appearance inclusions. Which will be the probable cause?