ADENOVIRUS

DNA viruses first isolated from adenoidal tissue in 1953

ADENOVIRUS Family Adenoviridae Genus Mastadenovirus

Transmission electron micrograph of adenovirus Source- PUBLIC Health Image Library, CDC

ADENOVIRUS - Classification Subgroups- 6 subgroups (A-F), based on hemagglutination Serotypes (human) Common serotypes:- 1-8, 11, 21, 35, 37, 40 Enteric Adenoviruses belong to subgroup F

ADENOVIRUS – Classification Adapted from Fields Virology SUBGROUPSEROTYPES A12, 18, 31 B3, 7, 11, 14, 34, 35 C1, 2, 5, 6 D8-10, 19, 20, 22-30, 36-39, E4 F40, 41

ADENOVIRUS - Structure Non-enveloped DNA virus nm in size Linear ds DNA genome with core proteins

ADENOVIRUS EM APPEARANCE

ADENOVIRUS - Ultra structure Icosahedral capsid with 252 capsomeres (12 pentons at vertices and 240 hexons) Each penton has a fibers with terminal knob projecting from it

Adenovirus- 3 D structure

ADENOVIRUS STRUCTURE

Adenovirus - EM appearance

ADENOVIRUS-Ultrastructure

Structure

Pathogenesis and Replication Infects mucoepithelial cells of respiratory, GI and GU tracts Enter via epithelium, replicate and spread to lymphoid tissue Viremia occurs Secondary involvement of viscera

Pathogenesis and Replication (contd.) Fiber protein determines target cell specificity and attachment Viral DNA enters host cell nucleus Virus replicates in cytoplasm

Adenovirus- replication

Replication (contd.) Early and late phases of replication Error-prone process Inclusion bodies in nucleus

ADENOVIRAL INCLUSION BODIES

Types of infection Lytic Latent/occult Oncogenic Transformation

Types of infection Lytic Results in cell death; seen in mucoepithelical cells Latent/occult Virus remains in host cell; seen in lymphoid tissue, Groups B and C Oncogenic Transformation Uncontrolled cell growth and replication occur; seen with Group A viruses in hamsters

Adenovirus Used as VECTORS to transfer desired genetic material into cells Viral genome is relatively easily manipulated in vitro Efficient expression of inserted DNA in recipient cell

Adenovirus- Properties Stable in the environment Relatively resistant to disinfection (Alcohol, chlorhexidine, detergents) Stable in GI tract- can withstand low pH, bile acids and proteolytic enzymes

Time-course of infection Incubation period days Infective period continues for weeks Intermittent and prolonged rectal shedding Secondary attack rate within families up to 50%

Timecourse - Respiratory infection Source- Medical Microbiology, 5 th Edition (Murray, Rosenthal, and Pfaller)

EPIDEMIOLOGY Endemic, epidemic and sporadic infections Many infections are sub-clinical

EPIDEMIOLOGY-contd. ’Tip of the iceberg phenomenon’ Classical disease presentation Mild clinical disease Asymptomatic infection but +infectivity

EPIDEMIOLOGY- Outbreaks Military recruits, swimming pool users, hospitals, residential institutions, day care settings

EPIDEMIOLOGY-transmission Prolonged infective period (weeks) Intermittent and prolonged rectal shedding Stable in the environment

TRANSMISSION Droplets Fecal-oral route Direct and through poorly chlorinated water Fomites

CLINICAL SYNDROMES Respiratory Eye Genitourinary Gastrointestinal Others

Acute Respiratory Disease (LRI) Fever Tracheobronchitis Pneumonia Children and adults Epidemics in military recruits Types 4 and 7 most frequently

Acute Respiratory Disease

Pharyngoconjunctival fever Headache, fever, malaise Conjunctivitis and Pharyngitis Cervical adenopathy, rash and diarrhea also Main adenovirus types: 3, 4, 7, 14 Epidemics in summer months Contaminated water in swimming pools, fomites

Adenoviral Infections of the eye Epidemic Keratoconjunctivitis (EKC) Acute follicular conjunctivitis Pharyngoconjunctival fever

Adenoviral conjunctivitis Early conjunctivitis (top) and Bilateral conjunctivitis (lower)

Epidemic Keratoconjunctivitis Incidence in summer Types 8, 19, 37 Outbreaks- in situations of close contact (e.g., schools, hospitals, camps, nursing homes, workplaces) Spread via droplets and contaminated water (ophthalmologic solutions and equipment, swimming pools), fomites, hands

EKC-Clinical features SYMPTOMS Pink/red eye Irritation, tearing, foreign- body sensation Ocular pain Photophobia Fever, malaise Respiratory symptoms SIGNS Conjunctival injection, ecchymosis Corneal injection (limbus) Diffuse→focal epithelial keratitis ↓Visual acuity (subepithelial corneal opacities) Ipsilateral pre-auricular lymphadenopathy

Gastrointestinal Infections Types 40, 41 Age <4 years Spread via fecal-oral route Year round

Gastrointestinal Infections- (contd.) Incubation period 3-10 days Diarrhea lasts for days Fever Also, intussusception, mesenteric adenitis, appendicitis

INTUSSUSCEPTION

ADENOVIRAL INFECTIONS- Genitourinary system Acute hemorrhagic cystitis fever, dysuria, hematuria Types 11, 7, 4, 21, 1 More common in boys Others Orchitis, nephritis, cervicitis with ulcerated vesicular lesions, urethritis Types 2, 8, 19, 37

Other Infections due to Adenovirus Myocarditis Pericarditis Meningitis Rash Arthritis

Adenovirus infections in Immunocompromised hosts Disseminated, severe and often fatal infections Due to new infection or reactivation of latent virus Prolonged infections with prolonged viremia and viral shedding Necrotizing pneumonia, hepatitis, rash, disseminated intravascular coagulation (DIC), CNS involvement

Adenovirus infection in the immunocompromised

DIAGNOSIS OF ADENOVIRAL INFECTIONS Variety of clinical specimens depending on clinical syndrome-NP, conjunctival, stool, urine, tissue, etc. Transport in viral transport media Isolation from pharyngeal site correlates better with current clinical infection

Methods for diagnosis Culture in HeLa, HEK cell lines Shell vial cell culture DFA PCR, nucleic acid probes EM and Immune EM

Diagnosis- Enteric adenoviruses Isolation requires special media-Graham 293 ELISA for rapid detection is available

Prevention Good handwashing Contact precautions Chlorination of water Disinfection or sterilization of ophthalmologic equipment Use of single dose vials Oral vaccine- restricted use

ADENOVIRUS VACCINE Oral live attenuated vaccine Strains 4, 7 Used in military recruits Manufacture of vaccine was halted in 1996 Lapse in immunization was associated with outbreaks in military recruits