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-oUK ~ peer wens anogenital HPV infect _ ng ADENOVIRIDAE ssed : Adenoviridae family consists of we organ * Aviadenovirus: Infects birds * Mastadenovirus: Infects mammals inc Human adenoviruses are further serotyp re assay antigenic types which are divided into g specific based on the following Properties: and E7 * Ability to agglutinate RBCs rats sof + Oncogenic potential in animals (rats) or cell lines (they are non-malignant to humans) } + Guanine-plus-cytosine (G+C) content of DNA. lor anal Group I adenoviruses include Serotypes 12, 18 and 31. They have Maximum oncogenic potential, but are lowest in G+C Content. It is also the only group that does not agglutinate monkey or rat RBCs, two 8enera: luding humans ed into 51 distinc ix groups (Ito vy from either Monkeys or CHapy; US. 43 6 4 vow a ip oP uses have the following properties gente non-enveloped, 70-90 nm in sing @ * Posse, es 25° Hey eres 7 ca pedral symmetry with ber proteing Project a «+ Kg vertex (unique Property) This gives yniensiiom , Y sft shaped appearance Fig. 3.) alspace ' we in a linear dsDNA. a yeyeontain al : thogenesis and Clinical Manifestations a jnovruses infect and eeplicate in the gpiay } por the repo TAL YC, eastoinegsetei | etait and liver, Though onecqyene esc | uniypes can cause human diseases, type 4 oF the seenon wore Single serotype may gage Me Sal mfestations and conversely, more than ome stHerem, 5 « mise the same clinical illness, pemay *! caespiratory diseases ; * 4 Upper respiratory tract infection in ¢ . hildren caused by serotypes 1, 2, 3.and5 mainly 1 Pneumonia: Adenoviruses particutar| and 21 are responsible for about 10-20% of ees 2 niin childhood heumo, = Acute respiratory disease syndrome o a among military reeruit—are commonly snttonks with type 4, 7 and occasionally type 3, a Ocular infections: 2 Pharyngoconjunctival fever: It tends to creas at res summer cape qc swimming pool conjunctivitis), and ig san with types 3 and 7 is associated Fig. 43.3: Adenovirus schematic diagram) ® Epidemic keratoconjunctivitls or shipyard eye: Woveurs mainly in adults and is highly contagious, caused by types B, 19. and 37. Infantile gastroenteritis: Serotype 40 and 41 may account for §-15% of cases of viral gastroenteritis in young children Acute hemorrhagic cystitis in children, especially in boys-caused by serotypes 1] and 21 Immunocompromized patients are at higher risk of developing serious pneumonia Transplant recipients may develop pneumonia, hepatitis, nephritis, colitis, encephalitis and hemorrhagic cystitis. Types $4 and 35 are isolated commonly from transplant recipients, Laboratory Diagnosis + Specimen collection: Depending on the manifestations, various specimens such as throat swab, conjunctival swab, stool or urine may be collected * Virus isolation: Primary human embryonic kidney cell line and A 549 cell line are the most susceptible cell lines. Others such as HEp-2, HeLa, and KB cell lines can also beused ® Viral growth can be detected by: Characteristic cytopathic effect: Rounding and grape-like clustering of swollen cells Antigen detection by direct-IF test. ® Reporting: Reporting should be done cautiously when adenovirus is recovered from throat or stool as they can persist for long duration in the gut and in adenoids and shed intermittently in the setting of other infections 2 Shell vial technique can be performed prior to cell culture to enhance viral replication so that detection time can be reduced = Explant culture: Adenoviruses (especially group-C) can grow on adenoid explants, however, it is no longer in use now. 4 Serotyping: Type specific antigens (viral capsid proteins) can be identified by hemagglutination test (targeting HA antigens) and neutralization test (targeting capsid proteins) | & Direct IF test: It can be employed to detect adenoviral antigens from clinical samples such as throat or conjunctival secretions by using fluorescent tagged anti- hexon antibody ‘ Fastidious enteric serotypes such as type 40 and 41 from stoolThey can be detected by electron microscopy or by i tection by ELISA * wolenlar methods: PCR has been available targeting group-specific conserved hexon or fiber genes, Multiples PCR followed by sequencing is done for detection o adenovirus types. PCRs rapid and more sensitive than fa Soe conventional culture. Real-time PCR is used to monitor viral load, which is useful for immunocompromised and transplant recipients . Serum antibody detection: It can be done by various tests such as CFT, neutralization test, ELISA, or rarely hemagglutination inhibition test (HAI) for few hemagglutinating serotypes. Treatment and Control There is no specific antiviral drug available. Only symptomatic treatment is given. General Preventive Measures +» Effective hand washing: Use of paper towels is better than cloth towels for hand drying ‘ “ Sodium hypochlorite to disinfect environmental surfaces * Chlorination of swimming pools and waste water should, , be followed to prevent waterborne conjunctivitis or i gastroenteritis “> Strict asepsis during eye examinations. Live Adenovirus Vaccine Live adenovirus vaccine containing types 4 and 7 has been used in military recruits. a + Itwas available as gelatin coated capsules and given orally It was highly effective, but not in use since 1999 due to manufacturer issues. There are plans to develop this : In vaccine again. % Adenoviruses used for Gene Therapy < Replication defective adenoviruses can also be used as live- . virus vectors for the delivery of vaccine antigens and for gene therapy; eg. trials on adenovirus vectored M. tuberculosis (using 85A antigen) and HIV vaccines. DA I. Adenoviruses Class Resistan Immunity G. Prophylaxis viruses were first detected from human adenoid Miaeqleno, from adenoid). They belong to family ss vidoe, These are non-enveloped, icosahedral, DNA ae tat replicate in the nucleus of infected eel ADENOVIRUSES A.Classification Adenoviruses are grouped into two genera, Aviadenovirus ‘ble $6.1 Classification of Human Adenoviruses ADENOVIRUS 2, Morphology D, Pathogen FB Laboratory Diagnosis . Adenovirus-Associated Viruses (AAV) and Mastadenovirus. They possess avian and mammalian adenoviruses respectively, Human adenoviruses are divided into 7 species (previously named as subgenera)— A to G. Species B has been divided into two subspecies BI and 2. These species contain about 52 human adenovirus serotypes (Table 56.1), All adenoviruses share a common. complement fixing antigen. Type specific antigenic determinants are present on the pentons and fibres. A 12, 18, 31. High a 3,7, 16, 21, 50 Monkey (complete) Weak R11, 14,34, 35 Monkey (complete) Weak 1256 Rat (partial) None of low $410, 13, 15, 17, 19, 20, 22-30, 32, 33, 3639, 42-49, Rat (complete) Nave be san ann it ee Rat (partial) None of low Fo toa Rat (partial) none ie Not determined Not known ‘Total serotypes | to 52 *2Maealaination is ither complete or partial. 465 466 Q_ Unit IV: Virology . Morpholo: r aecoine is ns nm in diameter with an ee capsid containing double stranded DNA. Eac! capsid s made of 252 capsomers, arranged as icosahedron oi triangular facets and 12 vertices. Of the 252. capsomers, 2 ‘d hhexons make up the 20 traingular facets of icosahedron and 12 pentons form the vertices. From each penton projects on apical fibre that serves to bind specifically to receptor sit on the host cell, Each penton unit consists of @ penton base anchored in the capsid and an apical fibre consisting of a rod like portion with a knob attached at the distal end. This makes the appearance of the virion as a space vehicle (Fig. 56.1). Fig. 56.1 Morphology of adenovirus C. Resistance Adenoviruses remain viable for about a week at 37°C but are readily inactivated at 50°C. They resist ether and bile salts, D, Pathogenesis Adenoviruses cause infections of the respiratory tract, eye, gastrointestinal tract and urinary tract (Table 56.2), Infection occurs through conjunctiva or nasal mucosa. Faeco-oral spread, particularly among children can also Table 56.2 Diseases Associated with Various Serotypes of Adenoviruses ‘Acute respiratory disease Pneumonia Pharyngoconjunctival fever 3,4, 11 Acute follicular conjunctivitis 8, 19,37 Epidemic keratoconjunctivitis 40, 41 Diarrhoea and vomiting 1,25 Intussusception 1,21 Haemorthagic cystitis 19, 37 Genital infections 5, 34, 35, 43-47 Disseminated infection occur. Inc multiply i intestine @ to 8accou Acute fet C viruse: B viruse gastroent while I 3,4 and | ‘The obse in baby of thes: evidence: E. Imm Adenoy antiboc FRLab 1. Spe Throat conjur genita’ 2. Mir Viral micro tract, demo antib 3.181 Viru: by in as E The ‘swol seat period ranges from 5.7 ett TF cially in the conjunctiva, phar, My, lift pond drain mph nos ¢ ines mosis associated withage te 19 82000" ‘ile pharyngitis is mainly caused by ing acute FPR F acute respiratory diseases py Subp, “Serotype 40 and 4 may cause 3 : its, er0UrPe 8: 19 and 37 lead to eye int es nd 37 may also cause genital infections ¢, Me, jie! onsble for acute folcular cons 3,4and 11 af that some adenoviruses produce sesatohad led t stules on the posse in baby basics in malignancy. However, “hes al relating adenoviruses to human _ evidence a Immunity ‘Adenoviruses int ‘antibodies protec Laboratory Diagnosis 1, Specimens Throat swab, nasopharyngeal aspirate, bronchial lay, conjunctival swab, corneal scraping, urine, anal sgh senital secretions and biopsy. duce long-lasting immuni M, infants from adenoviruses! 2, Microscopy Viral particles may be seen directly in stool by electea icroscopy. Viral antigens in the cells from respiratory tract, eye, urine and infected cell cultures may be demonstrated by immunofluorescence using monoclonal antibodies. 3.[solation Virus may be isolated from the throat, eye, urine or Fass by inoculating the clinical specimen in tissue cultures sch as HeLa, Hep-2, KB and human embryo kidney cell ‘The cytopathic effects include rounding and clustering of swollen cells into grape-like clusters. Identification is dont by immunofluorescence, CFT and haemagelutination tests. Typing is done by neutralisation tests. 4 latex Agglutination Test Enteric adenoviruses may be detected by using lee Particles coated with specific antibody. 5. Polymerase Chain Reaction 1's the most sensitive technique for antigen det i“ apid method for detecting all the human serotypes 6.Setology Ri bine deat of antibodies should be demonstrated Sera. Examination of a single specimen of ©" «ve as adenovirus antibodies are so common sive clustv™ ation. 1 i popu! att? xis rope existence of several serotypes and s, vaccines are not oO! i iB . part of adenovirus infection: id nature grail 4 ApeNOVIRUS-ASSOCIATED VIRUSES GAY) ; ral viral particles (20-25 nm in diameter) Small icosahed! n-enveloped, icosahedral, D 1. Adenoviruses are no’ hicle. 2. The appearance of adenovirus is like a space vel ‘ They cause infections of the respiratory tract, eye A : enovirus-associated viruses (AAV) are unt gastrointestinal t able to multiply except in ce Ch 56: Adenoviruses J 67 have been found in several adenovirus preparat by electron microscopy. These particles are multiply except in cells simultaneously in adenoviruses. These are named as aden viruses (AAV) or adenosatellite viruses. They can be detected by electron microscopy and CFT or im fluorescence with specific antisera. Types 1,22 of human origin, while type 4 is of simian 01 pathogenic role is uncertain. They have been class in the Parvovirus family. ne NA viruses. ract and urinary tract. sly infected with adenoviruses. ls simultaneou

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