ADENOVIRUS

ADENOVIRUSDNA viruses first isolated from adenoidal tissue in 1953

ADENOVIRUSFamily 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- 1-49 (human)

Common serotypes:- 1-8, 11, 21, 35, 37, 40

Enteric Adenoviruses belong to subgroup F

ADENOVIRUS – Classification Adapted from

Fields Virology

SUBGROUPSUBGROUP SEROTYPESSEROTYPES

A 12, 18, 31

B 3, 7, 11, 14, 34, 35

C 1, 2, 5, 6

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

E 4

F 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 infectionSource- 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)

FeverTracheobronchitisPneumoniaChildren and adultsEpidemics in military recruitsTypes 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 10-14 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