15/05/14371 Adenoviruses

2 Introduction: Name: adenoids, site of initial isolate from human. Site of infection & disease production: Eye. Respiratory tract. Gastrointestinal tract. Urinary tract & genital tract. Eye. Respiratory tract. Gastrointestinal tract. Urinary tract & genital tract. Types: 51 known human serotypes. One third of them are responsible for most cases of human infection. One third of them are responsible for most cases of human infection. Oncogenicity: Group A ( type 12,18,31), highly tumerogenic, & serve as models for cancer induction in animals.

15/05/14373 Properties of adenoviruses : Shape: Icosahedral. Size: medium size (70 -90) nm. Non-enveloped. Fibers are projected from each vertex. Viral genome:( Linear, double stranded DNA, size kbp). Capsid composed of 252 capsomeres,12 penton capsomeres at the vertices with fiber projection from each of the 12 vertices. The rest of capsid is composed of 240 hexon capsomeres. Site of their replication: nucleus of infected host cell. Electrone Microscope Schematic diagram

15/05/14374 Viral proteins include: 1- Hexon capsomeres. 1- Hexon capsomeres. 2- Penton capsomeres. 2- Penton capsomeres. 3- Fibers (projections). 3- Fibers (projections).Hexons: all human adenoviruses display this common hexon antigenicity. all human adenoviruses display this common hexon antigenicity.Pentons: Situated at the vertices of the capsid & have fibers protruding from them. Situated at the vertices of the capsid & have fibers protruding from them. Functions: 1- Toxin like activity that cause rapid appearance of CPE. 2- It carries the group specific antigen. Functions: 1- Toxin like activity that cause rapid appearance of CPE. 2- It carries the group specific antigen.Fibers: 1- Contain type specific antigen, used in serotyping. 2- have hemagglutinating activity. 1- Contain type specific antigen, used in serotyping. 2- have hemagglutinating activity.

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6 (Classification) Family, subfamilies, groups, serotypes Adenoviruses infect wide rang of animal species & grouped into two genera: 1- Aviadenoviruses (infect birds). 1- Aviadenoviruses (infect birds). 2- Mastoadenoviruses (infect mammals). 2- Mastoadenoviruses (infect mammals). There are 51 distinct antigenic serotypes isolated from humans. Human adenoviruses are divided into six group (A,B,C,D,E,F), on the basis of their physical, chemical & biological properties. Classification schemes for human adenoviruses: Group A (3 serotypes): 12, 18, 31. Group A (3 serotypes): 12, 18, 31. Group B (9 serotypes): 3, 7, 11, 14, 16, 21, 34, 35, 50. Group B (9 serotypes): 3, 7, 11, 14, 16, 21, 34, 35, 50. Group C (4 serotypes): 1, 2, 5, 6. Group C (4 serotypes): 1, 2, 5, 6. Group D (32 serotypes): 8- 10, 13, 15, 17, 19, 20, , 32, 33, , , 51. Group D (32 serotypes): 8- 10, 13, 15, 17, 19, 20, , 32, 33, , , 51. Group E (1 serotypes): 4. Group E (1 serotypes): 4. Group F ( 2 serotypes): 40, 41. Group F ( 2 serotypes): 40, 41.

15/05/14377 Group have the following shared characteristics: 1- Fibers length. 1- Fibers length. 2- DNA homology ( more than 90%). 2- DNA homology ( more than 90%). 3- Similar capacity to agglutinate erythrocytes. 3- Similar capacity to agglutinate erythrocytes. 4- Produce & behave similarly with respect to epidemiological spread & disease association. 4- Produce & behave similarly with respect to epidemiological spread & disease association.

15/05/14378 Pathogenesis Source: human ( patients, asymtomatic excreter). Transmission: Respiratory droplets, feco-oral route. Route of entry : Respiratory tract, GIT, Eye. Site of multiplication: The adenovirus infect & replicate locally in the epithelial cells of the eye, respiratory, GIT, & urinary bladder. Spread: virus usually do not spread beyond the regional lymph node. Latent: group C persist as latent infection in the adenoid & tonsil for years & shed in the feces for many months after initial infection. Single serotype may cause different clinical diseases & more than one type may cause the same clinical illness.

15/05/14379 Clinical infections: Adenoviruses of serotypes (1 – 7) most common types associated with illness. Adenoviruses of serotypes (1 – 7) most common types associated with illness. I- Respiratory diseases: Adenoviruses responsible for about 5% of acute respiratory disease in children < 5 years, but less in adults. Adenoviruses responsible for about 5% of acute respiratory disease in children < 5 years, but less in adults. 1- Acute febrile pharyngitis: Infants & children. group C viruses. Symptoms: sore throat, fever, & cough. Infants & children. group C viruses. Symptoms: sore throat, fever, & cough. 2- Pharyngeoconjunctival fever: Occur among children as outbreaks in swimming pool. Group B viruses types 3, 7, & 14. Occur among children as outbreaks in swimming pool. Group B viruses types 3, 7, & 14. Symptoms: acute febrile pharyngitis with conjunctivitis. Symptoms: acute febrile pharyngitis with conjunctivitis. 3- Acute respiratory disease: Epidemic form among military recruits under condition of fatigue, stress & crowding. types 4, 7, & occasionally type 3. Symptoms: fever, pharyngitis, sore throat, nasal congestion, cough, sometime pneumonia. Symptoms: fever, pharyngitis, sore throat, nasal congestion, cough, sometime pneumonia. 4- Adenoviral pneumonia: Adenoviruses particularly types 3, 7, & 21 are responsible for about 10-20% of pneumonias in childhood. Adenoviruses particularly types 3, 7, & 21 are responsible for about 10-20% of pneumonias in childhood.

15/05/ II. Eye infection: 1- Acute follicular conjunctivitis: Sometime associated with respiratory infection or as separate entity. Sometime associated with respiratory infection or as separate entity. 2- Epidemic keratoconjunctivitis: Serious disease & highly contagious. Serious disease & highly contagious. Serotypes: 8,19 & 37 group D. Serotypes: 8,19 & 37 group D. Clinically: follicular conjunctivitis & edema of the eyelid; pain lacrimation,& photophobia,subepithelial opacities in cornea can remain for up to 2 years. Clinically: follicular conjunctivitis & edema of the eyelid; pain lacrimation,& photophobia,subepithelial opacities in cornea can remain for up to 2 years. Vision loss is not typical. Vision loss is not typical. 3- Swimming pool conjunctivitis: Mild infection, summer outbreak, water borne, serotypes 3 & 7.

15/05/ III. Gastrointestinal disease Most human adenoviruses grow in the intestinal epithelium after ingestion but usually produce subclinical infections. Adenoviruses associated with gastrointestinal infection serotypes 40, 41. Types of Gastrointestinal diseases: 1- Infantile gastroenteritis: caused by enteric or fecal adenoviruses( type 40, 41). Enteric adenoviruses are difficult to be cultivated & are detected by EM & antigen based assay. Enteric adenoviruses are difficult to be cultivated & are detected by EM & antigen based assay. 2- Intussusceptions: Intussusceptions of infancy are associated to group C adenoviruses. 3- Coeliac disease: Structural homology between type 12 E1B protein & component of alpha gliadine (protein present in wheat) known to activate celiac disease.

15/05/ IV. Other diseases 1- Acute hemorrhagic cystitis: almost exclusively in male children. symptoms: gross hematuria & dysuria, serotype 11. symptoms: gross hematuria & dysuria, serotype Male urethritis & cervical lesion: associated with type 37 (group D), sexual transmitted disease. associated with type 37 (group D), sexual transmitted disease. 3- Meningoencephalitis: Rare, adenovirus 3, 5, 6, 7 & 12. Rare, adenovirus 3, 5, 6, 7 & Adenovirus infection among immunocompromised patients: Clinically infection occur as: I- Sever adenoviral pneumonia: common problem among transplant patients. Clinically infection occur as: I- Sever adenoviral pneumonia: common problem among transplant patients. II - Adenovirus hepatitis: caused by type 5 in group C, among patients with liver transplants. II - Adenovirus hepatitis: caused by type 5 in group C, among patients with liver transplants.

15/05/ Laboratory diagnosis Nature of samples taken depend on the clinical disease & the affected sites. The virus may be recovered from throat, sputum, stool, rectal swab, conjunctival swab, & urine. I. Direct examination: I. Direct examination: a - EM : a - EM : to visualize the virus particles, to visualize the virus particles, b- ELISA: b- ELISA: to detect specific viral antigen. used in detection of enteric adenoviruses in fecal extract. to detect specific viral antigen. used in detection of enteric adenoviruses in fecal extract. C- Immunoflouresent test: C- Immunoflouresent test: to detect adenovirus antigen in respiratory secretion, by using anti serum to hexon antigen of adenovirus labeled with fluorescence. to detect adenovirus antigen in respiratory secretion, by using anti serum to hexon antigen of adenovirus labeled with fluorescence.

15/05/ II. Culture: Types of cell cultures: for the virus isolation require human cells like: a- Primary human embyonic kidney (HEK) are most susceptible. B- Human epithelial cell lines like HEP-2 & HELLA. Types of cell cultures: for the virus isolation require human cells like: a- Primary human embyonic kidney (HEK) are most susceptible. B- Human epithelial cell lines like HEP-2 & HELLA. Cytopathic effects of adenoviruses consist : Cytopathic effects of adenoviruses consist : 1- Marked rounding & enlargement of the infected cells. 1- Marked rounding & enlargement of the infected cells. 2- Aggregation of the infected cells in grape like clusters. 2- Aggregation of the infected cells in grape like clusters. 3- Infected cells develop round intranuclear inclusions body containing DNA. 3- Infected cells develop round intranuclear inclusions body containing DNA.  The isolate can be further identified by Immunoflouroscent test to detect group specific antigen using antibodies & culture fluid from infected cells.

15/05/ III. Nucleic acid techniques: PCR used for diagnosis of adenovirus infections in tissue sample or body fluids usually by using primers for conserved viral sequence which detect all serotypes. PCR used for diagnosis of adenovirus infections in tissue sample or body fluids usually by using primers for conserved viral sequence which detect all serotypes. IV. Serology: Infection of human with any adenoviruses stimulate a rise in complement fixing antibodies to adenovirus group antigens shared by all types. Infection of human with any adenoviruses stimulate a rise in complement fixing antibodies to adenovirus group antigens shared by all types. CF test is an easily applied method for detecting infection by any member of the adenovirus group. A fourfold rise or greater in antibodies titer between acute & convalescent phase sera indicate current infection with adenovirus.

15/05/143716Epidemiology 1- Adenoviruses exist in all part of the world, it present year - round. 1- Adenoviruses exist in all part of the world, it present year - round. 2- Spread by fecal oral route, respiratory droplets or contaminated fomites. 2- Spread by fecal oral route, respiratory droplets or contaminated fomites. 3- Contributes to 3-5% of all infectious illness in children, & 2-5% of all respiratory illness in general population. 3- Contributes to 3-5% of all infectious illness in children, & 2-5% of all respiratory illness in general population. 4- Respiratory disease due to types 4, 7, & 3 is common among military recruits, & cause great morbidity. 4- Respiratory disease due to types 4, 7, & 3 is common among military recruits, & cause great morbidity. Prevention & control: Attempt to prevent & control adenovirus infection in the military have focused on vaccine. Attempt to prevent & control adenovirus infection in the military have focused on vaccine.Vaccine: A live attenuated virus vaccine contain types 4 & 7 grown in human diploid cell, recommended only for immunization of military population. A live attenuated virus vaccine contain types 4 & 7 grown in human diploid cell, recommended only for immunization of military population. Encased in gelatin coated capsules & given orally, to bypass the respiratory tract where it cause disease & released in intestine to produce subclinical infection that confirm a high degree of immunity against virus. Encased in gelatin coated capsules & given orally, to bypass the respiratory tract where it cause disease & released in intestine to produce subclinical infection that confirm a high degree of immunity against virus. Vaccinated persons respond with production of neutralizing antibodies. Vaccinated persons respond with production of neutralizing antibodies.