ADENOVIRUS

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ADENOVIRUS
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ADENOVIRUS

• DNA viruses first isolated from adenoidal tissue
  in 1953

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ADENOVIRUS

• Family Adenoviridae
• Genus Mastadenovirus

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Transmission electron micrograph of adenovirus
Source- PHIL, CDC
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ADENOVIRUS - Classification

• Subdivided into 6 subgroups based on
• hemagglutination (A-F)
• Human pathogens belong to 49 serotypes
• Common serotypes- 1-8, 11, 21, 35, 37, 40
• Enteric Adenoviruses belong to subgroup F

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ADENOVIRUS - Structure

• Non-enveloped DNA virus
• 70-90 nm in size
• Linear ds DNA genome with core proteins

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ADENOVIRUS EM APPEARANCE
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ADENOVIRUS - Ultrastructure

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

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Adenovirus- 3 D structure
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Adenovirus - EM appearanceNote- projecting
fibers and terminal knob
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ADENOVIRUS-Ultrastructure
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ADENOVIRUS STRUCTURE
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Structure
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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

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Pathogenesis and Replication (contd.)

• Fiber protein determines target cell specificity
  and attachment
• Viral DNA enters host cell nucleus
• Virus replicates in cytoplasm

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Adenovirus- replication
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Replication (contd.)

• Early and late phases of replication
• Errror-prone process
• Inclusion bodies in nucleus

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ADENOVIRAL INCLUSION BODIES
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Types of infection

• Lytic
• Latent/occult
• Oncogenic Transformation

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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

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Adenovirus

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

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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

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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

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Timecourse - Respiratory infectionSource-
Medical Microbiology- Murray, Rosenthal, Kobayshi
and Pfaller
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EPIDEMIOLOGY

• Endemic, epidemic and sporadic infections
• Many infections are subclinical

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EPIDEMIOLOGY-contd.Tip of the iceberg
phenomenon

• Classical disease presentation
• Mild clinical disease
• Asymptomatic infection
• but infectivity ()

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Epidemiology of Adenoviral Infections(source-cent
ers for disease control and prevention)
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EPIDEMIOLOGY

• Outbreaks noted in military recruits,
• swimming pool users, hospitals,
• residential institutions, day care settings

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EPIDEMIOLOGY-transmission

• Prolonged infective period (weeks)
• Intermittent and prolonged rectal shedding
• Stable in the environment

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TRANSMISSION

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

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CLINICAL SYNDROMES

• Respiratory
• Eye
• Genitourinary
• Gastrointestinal
• Others

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Acute Respiratory Disease (LRI)

• Fever
• Tracheobronchitis
• Pneumonia
• Children and adults
• Epidemics in military recruits
• Types 4 and 7 most frequently

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Acute Respiratory Disease
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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

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Adenoviral Infections of the eye

• Epidemic Keratoconjunctivitis (EKC)
• Acute follicular conjunctivitis
• Pharyngoconjunctival fever

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Adenoviral Infections of the eye
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Epidemic Keratoconjunctivitis

• Incidence in summer
• Conjunctivitis usually followed by keratitis
• Headache
• Pre-auricular lymphadenopathy
• Types 8, 19, 37
• Nosocomial spread by fomites, hands,
  ophthalmologic equipment, medications

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Gastrointestinal Infections

• Types 40, 41
• Age lt4 years
• Spread via fecal-oral route
• Year round

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Gastrointestinal Infections- (contd.)

• Incubation period 3-10 days
• Diarrhea lasts for 10-14 days
• Fever
• Also, intussusception, mesenteric adenitis,
  appendicitis

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INTUSSUSCEPTION
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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
• Types 2, 19, 37

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Other Infections due to Adenovirus

• Myocarditis
• Pericarditis
• Meningitis
• Rash
• Arthritis

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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, DIC, CNS
  involvement

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Adenovirus infection in the immunocompromised
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DIAGNOSIS

• 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

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Methods for diagnosis

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

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Diagnosis-Enteric adenoviruses

• Isolation requires special media-Graham 293
• ELISA for rapid detection is available

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Prevention

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

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Autumn is here.