ADENOVIRUSES

Human Adenoviruses

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 DNA VIRUSES
All are DS except Parvoviridae
All replicate in the nucleus except Poxviridae

Icosahedral Complex
1- Poxviridae

Naked Enveloped
non-enveloped ether-sensitive
ether-resistant
1- Parvoviridae 1- Herpesviridae
2- Papillomaviridae 2- Hepadnaviridae
3- Polyomaviridae

4- Adenoviridae
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 Human Adenoviruses
• Adenoviruses were first isolated in 1935 from
human adenoid tissues.

• Since then, at least 49 distinct antigenic types

have been isolated from humans and many other
types from animals.

• All human serotypes are included in a single

genus within the family Adenoviridae.

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Adenovirus structure

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 Morphology

– ds-DNA viruses,
– medium sized in diameter 70-90nm ,
– icosahedral
– Nonenveloped

Antigenic structure
• All human Adenoviruses share a common group-specific
antigen.

• Type specific antigens are important in serotyping.

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 Morphology cont…

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 Classification
Adenoviruses are divided into six groups (A to F) based on:

– physical,
– chemical
– biological properties

Antigenic structure divides adenoviruses into:

- 49 serotypes:

- About 1/3 of the 49 known human serotypes are responsible

for most cases of Adenovirus disease.

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 Pathogenesis:

• Adenoviruses spread by:

– direct contact,
– respiratory droplets
– feco-oral route.

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 Pathogenesis:

• Adenoviruses infect and replicate in the epithelial

cells of the:
– pharynx,
– conjunctiva,
– urinary bladder
– small intestine.

They usually do not spread beyond the regional

lymph nodes EXCEPT IN THE IMMUNE
COMPROMIZED HOST.

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• The first is lytic infection, which
occurs in human epithelial cells
through an entire replication cycle.
• Results in cytolysis, cytokine
production, and induction of host
inflammatory response.
• Second is chronic or latent
infection, the exact mechanism of
which is unknown, which frequently
involves asymptomatic infection of
lymphoid tissue.
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 Pathogenesis:

• The virus has a tendency to become

latent in lymphoid tissue,

• The virus can be reactivated by

immunosuppression.

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 Pathogenesis cont…

From Medical Microbiology,

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5th ed., PG-MCB-
Ssuuna Charles
Murray, Rosenthal & Pfaller,
12
Mosby Inc., 2005,, Fig. 50-4. MLSO-MDLC
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 Replication Cycle
1) Absorption and Penetration
 Bind to cell surface receptor
 Enters cell by endocytosis
2) Transcription
 Early transcription- Codes for non-structural,
regulatory proteins
 Late transcription- Codes for replication
substrates and machinery
3) Assembly
4) Exit- Cell lysis

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Replication cycle cont…

(From Fields Virology, 4th

02/25/23 ed,Charles
Ssuuna Knipe &PG-MCB-
Howley, eds, Lippincott Williams
14
& Wilkins, 2001, Fig. 67-5.)
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 Clinical Syndromes:

• Adenoviruses cause primary infection in:

– children
– less commonly adults.

• Several distinct clinical syndromes are

associated with Adenovirus infection.

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CLINICAL SYNDROMES
A. Respiratory diseases:

B. Eye infections:

C. Gastrointestinal disease

D. Other diseases:

E. Adenoviral infections of the immune compromised

host

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A. Respiratory diseases:
• The most important etiological association of
adenoviruses is with the respiratory diseases.

• They are responsible for 5% of acute respiratory

diseases in:
– young children
– and much less in adults.

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A. Respiratory diseases:
Four different syndromes of respiratory infection have been
linked to Adenoviruses.

• Acute febrile pharyngitis:

– most commonly seen in infants and young children,
– symptoms include cough, stuffy nose, fever and sore throat.

• Pharyngo conjunctival fever:types3,4&7

– symptoms are similar to those of acute febrile pharyngitis but
conjunctivitis is also present.
– It tends to occur in outbreaks such as at children's summer camps
(swimming pool conjunctivitis).

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A. Respiratory diseases:
• Acute respiratory disease:
– is characterized by pharyngitis, fever, cough
and malaise.
– It occurs in an epidemic form among young
recruits under conditions of fatigue and
overcrowding

• Pneumonia: a complication of acute

respiratory disease in both children and
adults.

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 NOTE
Outbreaks & epidemic
adenovirus infections
• Pharyngo conjunctival fever:
– outbreaks
– in children's summer camps (swimming pool conjunctivitis).

• Acute respiratory disease:

– occurs in an epidemic form
– among young recruits

• Epidemic keratoconjunctivitis:

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 B. Eye infections:
• Mild conjunctivitis:
– can occur as a part of respiratory pharyngeal syndromes.
– Complete recovery with no lasting sequelae is the
common outcome.
– Can occur sporadically or in outbreaks.

• Epidemic keratoconjunctivitis: types 8,19 &37

• a highly contagious and a more serious disease occurring
mainly in adults.
• Corneal involvement may be followed by
various
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 C. Gastrointestinal
disease:
1. No disease association
1. Many Adenoviruses replicate in intestinal cells and are
present in the stools without being associated with
GIT disease.

2. Infantile gastroenteritis
1. Two serotypes (40, 41) have been etiologically
associated with infantile gastroenteritis.

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NOTE:

1. The enteric Adenoviruses are very difficult

to cultivate.
2. Lab diagnosis depend on direct detection

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 D. Other diseases:

• Acute haemorrhagic cystitis:

– types 11, 21 may cause acute haemorrhagic
cystitis in children especially boys.

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 E. Adenoviral infections of
the immune compromised host

(Multiple serotypes)

• The most common clinical manifestations are:

• pneumonia,

• hepatitis

• gastroenteritis.

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 Laboratory Diagnosis
• Direct detection:

• Isolation

• Serology

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 Laboratory Diagnosis
Direct detection:
• Virus particle by EM can be detected by direct
examination of fecal extracts

• Detection of adenoviral antigens by ELISA.

Enteric Adenoviruses

• Detection of adenoviral DNA by Polymerase chain

reaction: can be used for diagnosis of Adenovirus infections
in tissue samples or body fluids.

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Laboratory
Diagnosis
Isolation
• Isolation depending on the
clinical disease, the virus may
be recovered from throat, or
conjunctival swabs or and
urine.
• Isolation is much more
difficult from the stool or
rectal swabs

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 Laboratory Diagnosis
Serology
• Haemagglutination inhibition
&
• Neutralization tests can be used to
detect specific antibodies following
Adenovirus infection.

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 Prevention and control
• Careful hand washing is the easiest way to prevent
infection.

• Disinfection of Environmental surfaces with

hypochlorites.

• The risk of water borne outbreaks of conjunctivitis can

be minimized by chlorination of swimming pools.

• Epidemic keratoconjunctivitis can be controlled by strict

asepsis during eye examination.

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 Treatment
• Medical therapy is not indicated in
healthy hosts. However, adenoviral
keratitis has been treated with early
topical steroids to avoid loss of sight.
• Currently, specific therapy for adenovirus
infection, other than supportive and
symptomatic treatment, remains a matter
of Debate.

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 Treatment
Antivirals
• These agents inhibit viral DNA and
protein synthesis.
• Several drugs, such as cidofovir,
ribavirin, ganciclovir, and
vidarabine, have been used to treat
adenovirus infections, especially in
immunocompromised patients.
• The use of these medications has
been based on case reports and
clinical
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 Treatment
• Most infections are self-limiting in
the setting of a normal immune
response and do not warrant specific
therapy.
• IV Ribavirin 30 mg/kg IV (not to
exceed 2 g) loading dose, followed by
16 mg/kg IV (not to exceed 1 g) q 6h
for 4 days, followed by 8 mg/kg IV
(not to exceed 500 mg) for 3-6 days

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 Treatment
• Cidofovir (Vistide) 1 mg/kg IV over
1 h qd, 3 times/wk for minimum of 3
wk

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 Adenovirus vaccine
• Live non-attenuated adenoviruses, administered as
an enteric-coated tablet, which bypass the
respiratory epithelium and only replicate once they
reach the intestine. This causes an asymptomatic
infection of the gastrointestinal tract, and results
in a good neutralizing antibody response
• The risk of spread of vaccine virus in immunized
children has limited the large-scale testing of
vaccines against the common endemic serotypes 1, 2,
and 5 which are associated with acute respiratory
diseases.
• Live, wild type enteric coated vaccine for military
recruits
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Adenovirus use as a vector in
vaccines

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