1. ARBOVIRUSES. DNA-VIRUSES: HERPESVIRUSES. ADENOVIRUSES ARBOVIRUSES. DNA-VIRUSES: HERPESVIRUSES. ADENOVIRUSES By as. Kuchmak O.B. Microbiology, virology, immunology department

3. Common and important herpesviruses of humans include herpes simplex virus types 1 and 2, varicella-zoster virus, Epstein-Barr (EB) virus, and cytomegalovirus. Properties of the Viruses: All herpesviruses have a core of double-stranded DNA surrounded by a protein coat that exhibits icosahedral symmetry. The nucleocapsid is surrounded by an envelope.

5. HERPES SIMPLEX: Human Herpesvirus 1 (Herpes Labialis) & Human Herpesvirus 2 (Herpes Genitalis). Infection with herpes simplex virus may take several clinical forms. The infection is most often inapparent. The usual clinical manifestation is a vesicular eruption of the skin or mucous membranes. Infection is sometimes seen as severe keratitis, meningoencephalitis, and a disseminated illness of the newborn.

6. Cytopathic effect (infected cells develop intranuclear acidophilic inclusion and then undergo necrosis )

8. Herpes labialis (cold sores, herpes febrilis). This is the most common recurrent disease produced by type 1. Clusters of localized vesicles occur, usually at the mucocutaneous junction of the lips. The vesicle ruptures, leaving a painful ulcer that heals without scarring. The lesions may recur, repeatedly and at various intervals of time, in the same location. The permanent site of latent herpes simplex virus is the trigeminal ganglion.

9. Herpes labialis

10. Keratoconjunctivitis. The initial infection with herpesvirus may be in the eye, producing severe keratoconjunctivitis. Recurrent lesions of the eye appear as dendritic keratitis or corneal ulcers or as vesicles on the eyelids. With recurrent keratitis, there may be progressive involvement of the corneal stroma, with permanent opacification and blindness.

12. Genital herpes (herpes progenitalis). Genital herpes is characterized by vesiculoulcerative lesions of the penis of the male or the cervix, vulva, vagina, and perineum of the female. The lesions are more severe during primary infection and may be associated with fever, malaise, and inguinal lymphadenopathy. Type 2 virus remains latent in lumbar and sacral ganglia.

16. Neonatal herpes. Herpesvirus type 2 may be transmitted to the newborn during birth by contact with herpetic lesions in the birth canal. The spectrum of illness produced in the newborn appears to vary from subclinical or local to severe generalized disease with a fatal outcome. Severely affected infants who survive may have permanent brain damage.

17. The virus may be isolated from herpetic lesions (skin, cornea, or brain). The appearance of typical cytopathic effects in cell culture suggests the presence of herpesvirus in 18-36 hours. Scrapings or swabs from the base of early herpetic lesions contain multinucleated giant cells. Serology: The agent is then identified by neutralization test or immunofluorescence staining with specific antiserum. Antibodies appear in 4-7 days; can be measured by NT, IHT, CFT, RIA and reach a peak in 2-4 weeks. Laboratory Diagnosis

18. HV, immune fluorescence test

19. Varicella (chickenpox) is a mild, highly infectious disease, chiefly of children, characterized clinically by a vesicular eruption of the skin and mucous membranes. The causative agent is indistinguishable from the virus of zoster. Zoster (shingles) is a sporadic, incapacitating disease of adults (rare in children) that is characterized by an inflammatory reaction of the posterior nerve roots and ganglia, accompanied by crops of vesicles (like those of varicella) over the skin supplied by the affected sensory nerves. VARICELLA-ZOSTER VIRUS (Human Herpesvirus 3) (Chickenpox, Herpes Zoster, Shingles, Zona)

20. Both diseases are caused by the same virus. Varicella is the acute disease that follows primary contact with the virus, whereas zoster is the response of the partially immune host to a reactivation of varicella virus present in latent form in sensory ganglia. VARICELLA-ZOSTER VIRUS (Human Herpesvirus 3) (Chickenpox, Herpes Zoster, Shingles, Zona)

21. Pathogenesis & Pathology Pathogenesis & Pathology. Varicella: The route of infection is probably the mucosa of the upper respiratory tract. The virus probably circulates in the blood and localizes in the skin. Swelling of epithelial cells, ballooning degeneration, and the accumulation of tissue fluids result in vesicle formation. In nuclei of infected cells, particularly in the early stages, eosinophilic inclusion bodies are found.

22. pathogenesis Varicella virus, pathogenesis

23. Varicella Chickenpox

24. Pathogenesis & Pathology. Zoster: In addition to skin lesions — histopathologically identical with those of varicella — there is an inflammatory reaction of the dorsal nerve roots and sensory ganglia. Often only a single ganglion may be involved. As a rule, the distribution of lesions in the skin corresponds closely to the areas of innervation from an individual dorsal root ganglion. There is cellular infiltration, necrosis of nerve cells, and inflammation of the ganglion sheath.

26. Zoster Shingles

27. CYTOMECALOVIRUS (Human Herpesvirus 5) Cytomegalic inclusion disease is a generalized infection of infants caused by intrauterine or early postnatal infection with the cytomegaloviruses. The disease causes severe congenital anomalies. Cytomegalovirus can be found in the cervix of up to 10% of healthy women. Cytomegalic inclusion disease is characterized by large intranuclear inclusions that occur in the salivary glands, lungs, liver, pancreas, kidneys, endocrine glands, and occasionally, the brain. Most fatalities occur in children under 2 years of age. Inapparent infection is common during childhood and adolescence. Severe cytomegalovirus infections are frequently found in adults receiving immunosuppressive therapy.

28. Cytomegalovirus Inclusion Diseases. Electron micrograph of a single animal cell infected with the cytomegalovirus. The intranuclear inclusion body has a typical” owl-eyed” apearence.

29. Cytomegalovirus can cause persistent infection in various tissues, including those of the salivary glands, breasts, kidneys, endocervix, seminal vesicles and peripheral blood leukocytes. This persistent infection leads to chronic viral excretion by the involved organ. Transmission of virus is through contact with infected secretions. The average incubation period is four to six weeks. It should also be noted that the kidneys of organ donors can be a source of cytomegalovirus for the recipient, and that peripheral blood leukocytes have been implicated in the transmission of cytomegalovirus via blood transfusion. Pathogenesis.

30. Cytomegalovirus infection can result in one of three distinct clinical syndromes. Congenital cytomegalovirus infection: hepatospleno-megaly, retinitis, a petechial/purpuric skin rash, and involvement of the central nervous system (ventriculo-megaly, intracranial calcifications, etc). Clinical Manifestations.

31. Mononucleosis syndrome (fever, malaise, atypical lymphocytosis, pharyngitis and, rarely, cervical adenopathy or hepatitis) Third clinical entity is cytomegalovirus infection in severely immunocompromised individuals. In these patients, infection can involve the lungs, gastrointestinal tract, liver, retina, and central nervous system Clinical Manifestations.

32. EB (Epstein-Barr) virus is the causative agent of infectious mononucleosis and has been associated with Burkitt's lymphoma and nasopharyngeal carcinoma. EB HERPESVIRUS (Human Herpesvirus 4). Epidemiology. Epstein-Barr virus is transmitted by intimate contact. Pathogenesis. Epstein-Barr virus is tropic for B- lymphocytes.

33. Infectious mononucleosis Nasopharyngeal carcinoma

34. Burkitt's lymphoma

35. Oncogenic Properties: Herpesviruses have been linked with malignant diseases in humans : herpes simplex virus type 2 with cervical and vulvar carcinoma; EB virus with Burkilt 's lymphoma of African children and with nasopharyngeal carcinoma.

39. acute respiratory disease, pharyngoconjunctival fever, nonstreptococcal exudative pharyngitis, and primary atypical pneumonia

40. Laboratory Diagnosis. The viruses have been recovered from throat swabs, conjunctival swabs, rectal swabs, stools of patients with acute pharyngitis and conjunctivitis, and urine of patients with acute hemorrhagic cystitis. Virus isolations from the eye are obtained mainly from patients with conjunctivitis.

41. Laboratory Diagnosis. The viruses are isolated by inoculation of tissue cultures of human cells in which characteristic cytopathic changes are produced. A new serotype that has not been isolated in cell cultures can be detected by direct examination of fecal extracts by electron microscopy or by enzyme-linked immunosorbent assay.

42. Serology. In most cases, the neutralizing antibody titer of infected persons shows a 4- fold or greater rise against the type recovered from the patient in NT. The CF test, using the common antigen, is an easily applied method for detecting infection by any member of the group. A sensitive radioimmunoassay can measure serum antibody to type 5 fiber antigen. Laboratory Diagnosis.

44. The arthropod-borne viruses, or arboviruses, are a group of infectious agents that are transmitted by blood-sucking arthropods from one vertebrate host to another. They can multiply in the tissues of the arthropod without evidence of disease or damage. The vector acquires a lifelong infection through the ingestion of blood from a viremic vertebrate. All arboviruses have an RNA genome, and most have a lipid-containing envelope and consequently are inactivated by ether or sodium deoxycholate.

46.  Togaviridae Genus Alphavirus  Flaviviridae Genus Flavivirus  Bunyaviridae Genus Bunyavirus  Reoviridae Genus Orbivirus  Rhabdoviridae Genus Vesiculovirus  Arenaviridae Genus Arenavirus  Nodaviridae Current taxonomic status of some arboviruses

47. Structures of Alphaviruses

48. Principal medically important alphaviruses Virus Antigenic Clinical Syndrome VectorHostDistributio n Eastern equine encephalitis Encephalitis (EEE) MosquitoBirdsAmericas Western equine encephalitis Encephalitis (WEE) MosquitoBirdsNorth America Venezuelan equine encephalitis Febrile illness, encephalitis (VEE) MosquitoRodents, horses Americas

49. Virus Antigenic Clinical Syndrome VectorHostDistributio n Chikungun y (CHIK) Febrile illness, rash, arthralgia MosquitoPrimates, humans Africa, India, Southeast Asia O’nyong- nyong (ONN) Febrile illness, rash, arthralgia MosquitoPrimatesAfrica Sindbisc (SIN) Febrile illness, rash, arthralgia MosquitoBirdsNothern Europe, Africa, Asia, Australia Semliki Forest Febrile illness, rare encephalitis MosquitoBirdsAfrica

50. FIGURE Alphavirus transmission. Virus abbreviations: Chik, chickungunya; RR, Ross River; May, Mayaro; ONN, O'nyong-nyong; SIN, Sindbis; EEE, eastern equine encephalitis; VEE, Venezuelan equine encephalitis.

51. Pathogenesis of alphaviruses

52. The rubella virus is a member of the genus Rubivirus in the family Togaviridae. Rubellaviruses

53. (German measles) is a common mild disease characterized by a rash. It affects children and adolescents worldwide and can also affect young adults. When rubella virus infects susceptible women early in pregnancy, it may be transmitted to the fetus and may cause birth defects. Therefore, accurate diagnosis is critical in pregnancy. Rubella

56. FIGURE. Clinical findings, virus shedding, and serologic response in postnatally acquired rubella.

57. Abnormalities Associated with Congenital Rubella Syndrome Type of defectsExamples Ocular defectsCataracts Microphthalmia Glaucoma Retinitis Heart defectsPatent ductus arteriosus Atrial septal defect Ventricular septal defect Peripheral pulmonic artery stenosis Hearing impairmentSensorineural deafness

58. Abnormalities Associated with Congenital Rubella Syndrome Type of defectsExamples Central nervous system Mental retardation Meningoencephalitis Progressive rubella panencephalitis (rare) Microcephaly OtherGrowth retardation Radiolucent borne disease Hepatosplenomegaly Hemathologic abnormalities: Thrombocytopenia, purpura Pneumonitis Endocrine dysfunction: Insulin dependent diabetes mellitus, thyroididtis

60. Cataract

61. Glaucoma

63. Structure of Flaviviruses

64. VirusAntigenic Clinical Syndrome VectorHostDistributio n Dengue (DEN) Febrile illness, rash, hemorrhagic fever, shock syndrome MosquitoHumansTropics, worldwide Yellow fever (YF) Hemorrhagic fever, hepatitis MosquitoPrimates, humans Africa, South America St. Louis encephalitis (SLE) EncephalitisMosquitoBirdsAmericas Principal medically important flaviviruses

65. VirusAntigenic Clinical Syndrome VectorHostDistributio n Japanese encephalitis (JE) EncephalitisMosquitoPigs, birdsIndia, China, Japan, South-East Asia West NileFebrile illness MosquitoBirdsAfrica, Middle East, Europe Tick-borne encephalitis (TBE) EncephalitisTickRodentEuropa, Asia Principal medically important flaviviruses

66. VirusAntigenic Clinical Syndrome VectorHostDistributio n Omsk hemorrhagic fever Hemorrhagi c fever TickMuskratsSiberia Kyasanur Forest disease (KFD) Hemorrhagi c fever TickRodentsIndia primates Principal medically important flaviviruses

67. Tick-born encephalitis virus

69. Human infection with both mosquito-borne and tick-borne flaviviruses is initiated by deposition of virus through the skin via the saliva of an infected arthropod (Fig). Figure. Pathogenesis of flaviviruses.

70. Yellow fever

71. Dengue fever

72. Bunyaviridae is a family of arthropod-borne or rodent-borne, spherical, enveloped RNA viruses. Bunyaviruses are responsible for a number of febrile diseases in humans and other vertebrates. They have either a rodent host or an arthropod vector and a vertebrate host.

74. Genus and Group VirusDiseas e VectorDistributi on Bunyavirus Bunyamwe ra FeverMosquitoAfrica Bwamba Fever, Rash MosquitoAfrica CaliforniaCalifornia encephalitis Encepha -litis MosquitoNorth America SimbuShuniFeverMosquitoAfrica, Asia Human diseases Caused by Viruses of the Family Bunyaviridae

75. Human diseases Caused by Viruses of the Family Bunyaviridae Genus and Group VirusDiseaseVectorDistributio n Phlebovirus Phlebovirus fever AlenquerFeverUnknownSouth America NaplesFeverSand flyEurope, Asia, Africa Rift Valley Fever Fever, encephalitis, hemorrhagic fever, blindness MosquitoAfrica SicilianFeverSand flyEurope, Africa, Asia

76. Human diseases Caused by Viruses of the Family Bunyaviridae Genus and Group VirusDiseaseVectorDistributio n Nairovirus Crimean- Congo Crimean- Congo hemorrhagic fever Hemorrhagic fever TickAfrica, Asia Nairobi sheep disease FeverTickAfrica, Asia

77. Human diseases Caused by Viruses of the Family Bunyaviridae Genus and Group VirusDiseaseVectorDistributio n Hantavirus HataanHantaanHFPS (hantavirus pulmonary syndrom) RodentAsia PuumalaHFPSRodentAsia SequlHFPSRodentAsia, Europe

78. Human diseases Caused by Viruses of the Family Bunyaviridae Genus and Group VirusDiseaseVectorDistributi on Genus unassigned BanguiFever, rashUnknownAfrica BhanjaFever, encephalitis TickAfrica, Europa, Asia Issk-kulFeverTickAsia KasokeroFeverUnknownAfrica NyandoFeverMosquitoAfrica TataguineFeverMosquitoAfrica WanowrieFever, hemorrhage TickMiddle East, Asia

79. FIGURE. Pathogenesis of bunyavirus infections. Humans are dead-end hosts of most bunyaviruses; however, the blood of Crimean-Congo hemorrhagic fever patients may be highly infectious.

80. Signs of Crimean-Congo Hemorrhagic Fever