1590 Adenovirus
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Transcript of 1590 Adenovirus
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