ADENOVIRUS

ADENOVIRUS
DNA viruses first isolated from adenoidal tissue in 1953

ADENOVIRUS
Family Genus
Adenoviridae Mastadenovirus

Transmission electron micrograph of adenovirus

Source- PUBLIC Health Image Library, CDC

ADENOVIRUS - Classification
Subgroups- 6 subgroups (A-F), based on hemagglutination
Serotypes- 1-49 (human) Common serotypes:- 1-8, 11, 21, 35, 37, 40 Enteric Adenoviruses belong to subgroup F

ADENOVIRUS Classification Adapted from

Fields Virology

SUBGROUP
A

SEROTYPES
12, 18, 31

B
C

3, 7, 11, 14, 34, 35

1, 2, 5, 6

D
E F

8-10, 19, 20, 22-30, 36-39, 42-49 4

40, 41

ADENOVIRUS - Structure
Non-enveloped DNA virus 70-90 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- 2-14 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, 5th 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, foreignbody sensation Ocular pain Photophobia Fever, malaise Respiratory symptoms

SIGNS Conjunctival injection, ecchymosis Corneal injection (limbus) Diffusefocal 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 10-14 days

Fever
Also, intussusception, mesenteric adenitis, appendicitis

INTUSSUSCEPTION

ADENOVIRAL INFECTIONSGenitourinary 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

DiagnosisEnteric 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