Dr.T.V.

Rao MD

Dr.T.V.Rao MD 1
Adenovirus Infections

 Adenoviruses most commonly cause respiratory illness;
however, depending on the infecting serotype, they may also
cause various other illnesses, such as gastroenteritis,
conjunctivitis, cystitis (bladder infection), and rash illness.
Symptoms of respiratory illness caused by adenovirus infection
range from the common cold syndrome to pneumonia, croup,
and bronchitis. Young infants and especially patients with
compromised immune systems are more susceptible to severe
complications of adenovirus infection. Acute respiratory
disease (ARD), which was first recognized among military
recruits during World War II, can be caused by adenovirus
infections.

Dr.T.V.Rao MD 2
 What are Adenoviruses
• Adenoviruses are a
group of medium
sized, nonenvelopedd,
double stranded DNA
viruses that share a
common complement
fixing antigen
• They infect humans
and animals

Dr.T.V.Rao MD 3
 Adenoviruses
 Adenoviruses are medium- 
sized (90-100 nm),
nonenvelopedd icosahedral
viruses containing double-
stranded DNA. There are at
least 52 immunologically
distinct types that can cause
human infections.
Adenoviruses are unusually
stable to chemical and
physical agents and to
adverse pH conditions, thus
allowing for prolonged
survival outside of the body.
Dr.T.V.Rao MD 4
 Morphology of Adenovirus
• The capsid contains
252 capsomers
arranged as
icosahedrons with
20 triangular facets
and 12 vertices
• 240 are called as
hexons
• 12 are called as
pentons.
Dr.T.V.Rao MD 5
Isolation of Adenovirus

 Adenoviruses were first
isolated in human
adenoids (tonsils), from
which the name is
derived. Adenoviruses
represent the largest
nonenvelopedd viruses,
because they are the
maximum size able to
be transported through
the endosome
Dr.T.V.Rao MD 6
 Classification
 Contain two genera
 Mastaadenovirus.

 Infects the mammals
 Aviaadenovirus
 Infects birds
 They infect only the homologues species with the
exception of oncogenic human adenovirus
 Type 12, 18,and 31 cause sarcoma when injected into
new born hamsters.
 Doctorrao'sslideshare

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 PROPERTIES

Composition:
• DNA (13%), protein (87%)

Genome:
• Linear, double stranded DNA, 26 – 45
kbp, protein-bound to termini,
infectious
Dr.T.V.Rao MD 8
 PROPERTIES
Proteins:
• 11 virion proteins
• Hexon & penton capsomeres are the
major components on the surface of
the virus particle
• Penton base with toxin-like activity
• Fibers – with type-specific antigens;
associated with hemagglutinating
activity Dr.T.V.Rao MD 9
 PROPERTIES
Replication: Early Events
• Induce the host cell to enter the S phase of the cell
cycle  create conditions conducive to viral
replication

Interaction of
Virus attachment
penton base with
(adsorption)
cellular integrins

NUCLEUS
Virus
Uncoating CYTOSOL internalization
into endosomes

Dr.T.V.Rao MD 10
 PROPERTIES
Virus Effects on Host Defense Mechanisms
• VA RNAs: prevent activation of an interferon-inducible
kinase that inactivates eukaryotic initiation factor 2
• E3 region proteins: inhibit cytolysis of infected cells by
host responses
 E3 gp19-kDa protein: blocks movement of MHC
class I antigen to the cell surface  protect from
CTL-mediated lysis
 Other E3-encoded proteins: block TNF-

Dr.T.V.Rao MD 11
 PROPERTIES
Virus Effects on Cells
• Oncogenes: E1A (pRB) and E1B (p53) –
animals such as hamsters
• Cytopathic for human cell cultures,
particularly primary kidney and continuous
epithelial cells
• CPE: marked rounding, enlargement, and
aggregation of affected cells into grape-like
clusters without lysis of infected cells

Dr.T.V.Rao MD 12
 Adenovirus Genome
The adenovirus genome is linear, non-
 (ds) DNA which is
segmented double stranded
around 30–38 Kbp. This allows the virus to
theoretically carry 30 to 40 genes Although this
is significantly larger than other viruses in its
Baltimore group it is still a very simple virus
and is heavily reliant on the host cell for survival
and replication. An interesting feature of this
viral genome is that it has a terminal 55
kDaprotein associated with each of the 5' ends of
the linear ds DNA, these are used as primers in
viral replication and ensure that the ends of the
virus' linear genomeDr.T.V.Rao
are adequately
MD replicated 13
Appear as Space Vehicle


Dr.T.V.Rao MD 14
 Adenoviruses are prevalent
all over the world
• Over 50 serotypes
are isolated
• Most of the recent
isolates are from
AIDS patients
• Infections are
common in children
and world wide
prevalence.
Dr.T.V.Rao MD 15
 Pathogenesis
Adenovirus cause

infections in
Respiratory tract
Eye, Urinary bladder,
and Intestines
More than one type
of virus may cause
clinically different
diseases
Dr.T.V.Rao MD 16
 Immunity

• Induce effective and long-lasting immunity against re-
infection
• Resistance to clinical disease directly related to presence
of circulating neutralizing antibodies – persist for life
• Type-specific neutralizing antibodies do not always prevent
re-infection
• Group-specific antibodies not protective and decline with
time
• Maternal antibodies protective for infants against severe
respiratory infections
Dr.T.V.Rao MD 17
 Clinical Features
• Clinical features: 
Adenoviruses most
commonly cause respiratory illness;
however, depending on the infecting
serotype, they may also cause various
other illnesses, such as gastroenteritis,
conjunctivitis, cystitis, and rash illness.
Symptoms of respiratory illness caused
by adenovirus infection range from the
common cold syndrome to pneumonia,
croup, and bronchitis.
Dr.T.V.Rao MD 18
 CLINICAL FINDINGS

RESPIRATORY DISEASES
• Cough, nasal congestion, fever, and sore throat 
most common in infants and children; usually
involving Group C viruses
• Types 3, 7, and 21: pneumonia (10-20%) in childhood
• Types 4 and 7 (and occ. Type 3): acute respiratory
disease among military recruits; occurs in epidemic
form

Dr.T.V.Rao MD 19
 Adenovirus infections are
important in Military Medicine

Adenoviruses are responsible for 3-5%
of acute respiratory infections in
children and 2% of respiratory illnesses
in civilian adults. They are more apt to
cause infection among military recruits
and other young people who live in
institutional environments. Outbreaks
among children are frequently reported
at boarding schools and summer
Dr.T.V.Rao MD 20
 Adenovirus - Pharyngitis
Major cause of
infections
associated with
nonbacterial
pharyngitis and
tonsillitis
Causes febrile
common cold
Types 1 – 7 are
common types Dr.T.V.Rao MD 21
Adenovirus Common cause
of Respiratory infections


Dr.T.V.Rao MD 22
Pneumonia - Adenovirus
Adenovirus types 3
and 7 are associated
with pneumonia
resembles like
atypical pneumonia
in adults.
Type 7 causes serious
and even fatal
pneumonia in infants
and young children
Dr.T.V.Rao MD 23
 ARD – Acute respiratory disease
with Adenovirus
Occurs usually
in military
recruits
Serotypes
4,7,and 21 are
agents
commonly
associated.
Dr.T.V.Rao MD 24
 Pharyngocongunctival
fever
• Occurs in civilian
population
manifest with
syndrome of febrile
Pharyngitis and
conjunctivitis
• Serotypes 3, 7, and
14 are associated.

Dr.T.V.Rao MD 25
 Epidemic
keratoconjunctivitis
Occurs with
serious
epidemic
Caused by
serotypes 8, and
less frequently
with 19, and 37.
Dr.T.V.Rao MD 26
 GASTROINTESTINAL DISEASE

GASTROINTESTINAL DISEASE

Types 40 and 41
• Associated with infantile gastroenteritis
• Account for 5-15% of viral gastroenteritis in
young children
• Abundantly present in diarrheal stools

Dr.T.V.Rao MD 27
A severe Adenoviral Infection


Dr.T.V.Rao MD 28
 Other manifestations

Acute follicular conjunctivitis, types 3,4
and 11 are responsible
Adenoviral and chlamydial conjunctivitis
are clinically similar
Diarrhoea – not conclusively established
Acute haemorrhagic cystitis in children
and types 11 and 21 are responsible
Mesenteric adenitis and intussusceptions
in children. Dr.T.V.Rao MD 29
 Adenovirus in
Immunocompromised

• Patients with
compromised immune
systems are especially
susceptible to severe
complications of
adenovirus infection.
Acute respiratory disease
(ARD), first recognized
among military recruits
during World War II, can
be caused by adenovirus
infections during
conditions of crowding
and stress.
Dr.T.V.Rao MD 30
 Immunity in Children
 Most children have

been infected by at
least one adenovirus
by the time they reach
school age. Most
adults have acquired
immunity to multiple
adenovirus types due
to infections they had
as children.
Dr.T.V.Rao MD 31
 Diagnosis of Adenoviral
Infections

Diagnosis: Antigen detection, polymerase
chain reaction assay, virus isolation, and
serology can be used to identify adenovirus
infections. Adenovirus typing is usually
accomplished by haemagglutination-
inhibition and/or neutralization with type-
specific antiserum. Since adenovirus can be
excreted for prolonged periods, the presence
Dr.T.V.Rao MD 32
 LABORATORY DIAGNOSIS
• SAMPLES should be collected from affected sites early
in the illness
• Duration of virus excretion varies among different
illnesses
 Throat of adults with common cold: 1 – 3 days
 Throat, stool, and eye for Pharyngocongunctival
fever: 3 – 5 days
 Eye for keratoconjunctivitis: 2 weeks
 Throat and stool of children with respiratory
illnesses: 3 – 6 weeks
 Urine, throat and stool of immunocompromised
patients: 2 – 12 months
Dr.T.V.Rao MD 33
 LABORATORY DIAGNOSIS

1. Virus isolation in cell culture

2. DNA hybridization or restriction endonuclease digestion
3. PCR
4. Electron microscopy
5. ELISA
6. Latex agglutination
7. Serology

Dr.T.V.Rao MD 34
 EPIDEMIOLOGY
• Usually do not cause outbreaks of disease
• Most common serotypes in clinical samples: low
numbered respiratory types (1, 2, 3, 5, 7) and the
gastroenteritis types (40 and 41)
• MOT: direct contact, fecal-oral route, respiratory
droplets, or contaminated fomites
• Infections with types 1,2,5, and 6 – chiefly during first
year of life
• Infection with types 3 and 7 – school years
• Infection with types 4,8 and 19 – adulthood
• Types 34 and 35 – bone marrow and renal transplant
recipients
Dr.T.V.Rao MD 35
 Treatment ?

No evidence-based guidelines for or against
specific antiviral therapies in this setting are
available, and treatment decisions should be
individualized; current evidence somewhat
favors treatment
Several case reports have described success
with cidofovir/ribavirin therapy for serious
adenoviral disease in immunocompromised
patients; however, the number of failed
treatments that have not been reported
Dr.T.V.Rao MD 36

remains uncertain.
 Prevention:

 Vaccines were developed for adenovirus serotypes 4
and 7, but were available only for preventing ARD
among military recruits, however, vaccine
production was stopped in 1999. Strict attention to
good infection-control practices, including contact
and droplet precautions, is effective for stopping
nosocomial outbreaks of adenovirus-associated
disease, such as epidemic keratoconjunctivitis.
Maintaining adequate levels of chlorination is
necessary for preventing swimming pool-associated
outbreaks of adenovirus conjunctivitis, and frequent
hand hygiene is recommended in group child care
settings. Dr.T.V.Rao MD 37
 Adenovirus as Vector in
Gene therapy
 Gene therapy using an

Adenovirus vector. A
new gene is inserted
into an adenovirus
vector, which is used to
introduce the modified
DNA into a human cell.
If the treatment is
successful, the new
gene will make a
functional protein.
Dr.T.V.Rao MD 38
 
Created by Dr.T.V.Rao MD for ‘e’
learning resources for Medical
professionals in Developing
World
Email
doctortvrao@gmail.com
Dr.T.V.Rao MD 39