Adenoviruses were first isolated in 1935 from human tissues. They are double stranded DNA viruses that can cause respiratory, gastrointestinal, and eye infections in humans. While many infections are mild, adenoviruses can cause pneumonia, gastroenteritis, and keratoconjunctivitis. Diagnosis involves isolating the virus from samples using cell culture or molecular techniques. Treatment focuses on symptom relief as there are no specific antivirals, though some drugs like cidofovir are being studied. Prevention emphasizes handwashing, pool chlorination, and infection control practices.

1. ADENOVIRUS
BY- SANJU SAH
ST. XAVIER’S COLLEGE, MAITIGHAR,KATHMANDU
DEPARTMENT OF MICROBIOLOGY

2. Introduction:
• Adenoviruses were first isolated in 1935 from human adenoid
tissues.
• Adenoviruses can replicate and produce disease in respiratory,
gastrointestinal and urinary tract and in the eye.
• Many adenovirus infection are subclinical and virus persist in
hosts for months.
• One third of 52 serotypes are responsible for most cases of
human adenovirus disease.
• Whereas a few types serve as models for cancer induction in
animal models

4. What are Adenoviruses
• Adenoviruses are a group of
medium sized, nonenveloped,
double stranded DNA viruses
that share a common
complement fixing antigen
• They infect humans and
animals
Classification:
Family :
Genus :
Species:
Adenoviridae
Mastadenovirus
Human adenoviru

5. Classification:
• Family Adenoviridae is classified into two genera:
• Mastadenovirus, the adenovirus of mammals.
• Aviadenovirus; adenovirus of birds
• At least 52 distinct antigenic types have been isolated from humans
and many other types from various animals.
• Human adenovirus have been divided into seven groups (A-G) on
the basis of their genetic, physical, chemical and biological
properties.
• They are divided into serotypes on the basis of type specific antigens
on penton bases and fibers.
• Serotypes are identified by neutralization tests.
• Different serotypes may cause infection or distinct diseases in
different age groups or patient populations

6. Neutralization tests
• Neutralization of a virus is defined as the loss of infectivity through
reaction of the virus with specific antibody.
• Virus and serum are mixed under appropriate condition and then
inoculated into cell culture, eggs or animals.
• The presence of unneutralized virus may be detected by reactions
such as CPE, haemadsorption/haemagglutination, plaque formation,
disease in animals.
• The loss of infectivity is bought about by interference by the bound
Ab with any one of the steps leading to the release of the viral
genome into the host cells.

8. Classification:
Classification schemes for Human Adenovirus

9. CHATERISTICS OF
ADENOVIRUS
• Adenoviruses are medium-sized (80 nm, nonenveloped
(naked) icosahedral viruses composed of a nucleocapsid and
a double-stranded linear DNA genome.
• There are over 52 different serotypes in humans, which are
responsible for 5–10% of upper respiratory infections in
children, and many infections in adults as well.

10. ADENOVIRUS
GENOME
• The adenovirus genome is linear, nonsegmented double stranded
(ds) DNA which is 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
kDa protein associated with each of the 5' ends of the linear
dsDNA.
• These are used as primers in viral replication and ensure that the
ends of the virus‘ linear genome are adequately replicated

11. Morphology of Adenovirus
• Adenovirus are 80 nm in size
• No envelope
• 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
• Each penton unit consists of penton
base anchored in the capsid and projection
or fibre consists of a rode like portion with a
knob attached at the distal end
• The virus appears like a space vehicle.

15. Replication
• Adenoviruses possess a linear dsDNA genome and are able to replicate in
the nucleus of vertebrate cells using the host’s replication machinery.
Adsorption and entry intohost
• Entry of adenoviruses into the host cell involves two sets of interactions
between the virus and the host cell.
• Entry into the host cell is initiated by the knob domain of the fiber protein
binding to the receptor.
• The two currently established receptors are: CD46 for group B human
adenovirus serotypes and the coxsackievirus adenovirus receptor (CAR)
for all other serotypes.
• There are some reports suggesting major histocompatibility
complex (MHC) molecules and sialic acid residues functioning in binding
of virus.

17. • Once the virus has successfully gained entry into the host cell, the
endosome acidifies, which alters virus topology by causing capsid
components to disassociate.
• These changes as well as the toxic nature of the pentons result in the
release of the virion into the cytoplasm.
• With the help of cellular microtubules, the virus is transported to the
nuclear pore complex, whereby the adenovirus particle disassembles.
• Viral DNA is subsequently released, which can enter the nucleus via
the nuclear pore.
• After this the DNA associates with histone molecules.
• Thus, viral gene expression can occur and new virus particles can be
generated.

18. • The adenovirus life cycle is separated by the DNA replication process
into two phases: an early and a late phase.
• In both phases, a primary transcript that is alternatively spliced to
generate monocistronic mRNAs compatible with the host’s ribosome
is generated, allowing for the products to be translated.
• The early genes are responsible for expressing mainly non-structural
and regulatory proteins.
• The function of these proteins are:
• Toalter the expression of host proteins that is necessary for DNA
synthesis;
• Toactivate other virus genes; and
• Toavoid premature death of the infected cell by the host-immune
defenses.

19. • Some Adenoviruses under specialized conditions can transform cells
using their early gene products.
• E1A (binds Retinoblastoma tumor suppressor protein) has been found
to immortalize primary cells in vitro allowing E1B (binds p53 tumor
suppressor) to assist and stably transform the cells.
• Nevertheless, they are reliant upon each other to successfully
transform the host cell and form tumors.
• The DNA replication separates the early and late phases.
• Once the early genes have liberated adequate virus proteins,
replication machinery and replication substrates; the replication of
the adenovirus genome can occur

22. • A terminal protein that is covalently bound to the 5’ end of the
adenovirus genome acts as a primer for replication.
• The viral DNA polymerase then uses a strand displacement
mechanism as opposed to the conventional Okazaki fragments used
in mammaliam DNA replication to replicate the genome of human
Adenoviruses.
• The late phase of the adenovirus lifecycle is focused on producing
sufficient quantities of structural protein to pack all the genetic
material produced by DNA replication.
• Once the viral components have successfully been replicated, the
virus is assembled into its protein shells and released from the cell as
a result of virally induced cell lysis.

24. Pathogenesis
• The recognized diseases of Adenoviruses predominantly involve the
respiratory tract, Gastrointestinal tract and eye.
• Virus may be introduced through contact, respiratory droplets or
ingestion.
• The association of particular types with specific disease syndromes is
striking.
• After recovery of illness, adenoviruses may maintain latent persistent
infections in the tonsils, adenoids and other lymphoid tissues of n.

25. Pathogenesis: (contd…)
Adenoviruses infect and replicate in the epithelial cells of the:
pharynx,
conjunctiva,
urinary bladder
small intestine.
• Infect and replicate in epithelial cells of respiratory tract, gastrointestinal
tract, urinary tract and the eye.
• Do not spread beyond regional lymph nodes.
• Group C persists as latent infections for years in adenoids and tonsils and are
shed in feces for many months after initial infection.
• Most adenovirus replicate in intestinal epithelium after ingestion but usually
produce sub clinical infection than overt symptoms.

26. • About 1/3 of human serotypes are commonly associated with human
illnesses.
• Single serotype may cause different clinical diseases and conversely
more than one serotype can cause same clinical illness.
• Adenoviruses 1-7 are more common types worldwide and account for
most instances of adenovirus associated illness.
• Responsible for 5% of respiratory diseases in young children but account
for much less in adults.
• Most infections are mild and self limited.
• Occasionally case disease in other organs particularly eye and
gastrointestinal tract.
Following are the clinical manifestation and disease caused by Adenovirus

28. CLINICAL
SYNDROMES
A. Respiratory diseases:
B. Eye infections:
C. Gastrointestinal disease
D. Other diseases:
E. Adenoviral infections of the immune compromised host

29. Respiratory Diseases:
• Typical symptoms: cough, nasal congestion, fever and sore throat.
• Symptoms most commonly manifested in infants and children and
usually involves group C viruses.
• Adenoviruses particularly 3, 7 and 21 are thought to be responsible for
about 10-20% pneumonias in childhood.
• Mortality rate of pneumonia 8-10% in very young.
• Also are cause of acute respiratory disease syndrome among military
recruits.
• Characterised by fever, sorethroat, nasal congestion, cough and malaise;
sometimes leading to pneumonia.

30. • Occurs in epidemic form among young military recruits under
conditions of fatigue, stress, and crowding soon after induction.
• Disease is caused by serotype 4 and 7 and occasionally by type 3.
• Outbreak of severe respiratory disease in 2007 caused by adenovirus
14 affects all age groups.

31. EYE
INFECTIONS:
• Mild occular involvement may be part of respiratory pharyngeal syndrome.
• Pharyngoconjunctival fever occurs as outbreak such as in children’s
summer camps (swimming pool conjunctivitis) and caused by type 3 and
7.
• Duration 1-2 weeks and complete recovery with no lasting sequela is
common outcome.
• Epidemic keratoconjunctivitis more serious disease; occurs mainly in
adults and is highly contagious.
• Source of infection: sinks and hand towel.
• Disease is characterises by acute conjunctivitis followed by keratitis
(inflammation of the cornea) that usually resolves in two weeks but may
leave subepithelial opacities in the cornea for up to two years.
• Caused by serotypes 8, 19 and 37

32. Pharyngoconjunctival
KERATOCONJUNCTI
VITIS
• Keratoconjunctivitis is inflammation of the cornea and conjunctiva.
• When only the cornea is inflamed, it is called keratitis
• when only the conjunctiva is inflamed, it is called conjunctivitis
• Pharyngoconjunctival fever is a condition characterized by a fever, sore
throat, and follicular conjunctivitis.

33. Gastrointestinal disease:
• Can often been isolated from feces but their relation to intestinal
disease has not been conclusively established.
• However two serotypes (types 40 and 41) have been etiologically
associated with infantile gastroenteritis.
• May account for 5-15% cases of viral gastroenteritis in young children.
• Adenoviruses 40 and 41 are abundantly present in diarrhoeal stools.
• Enteric adenovirus are very difficult to cultivate.
• Stool ELISA is often used for detection of these types.

34. Other Diseases:
• Cause variety of casual and severe diseases in immune compromised
patients.
• Most common problem in transplant patients is respiratory diseases
that may progress to pneumonia and may be fatal (usually types 1-7).
• Adenovirus hepatitis in children having liver transplant.
• AIDS patients mainly suffer from gastroenteritis due to
adenovirus.
• Types 11 and 21 may cause acute hemorrhagic cystitis ( is an
inflammation of the bladder) in children esp. boys.

35. Laboratory Diagnosis:
• Specimen:
• May be isolated from body fluids, eye swabs, throat swabs, throat
washings, urine, faeces and CSF.
• Samples should be collected from affected sites as early as possible.
• Duration of excretion of the virus varies among various
clinical illness;
• 1-3 days from throat of adults with common cold,
• 3-5 days for throat, stool and eyes, for pharyngoconjunctival fever,
• 2 weeks eye for keratoconjunctivitis,
• 3-6 weeks, throat and stool of children with respiratory illness,
• 2-12 months in stool, throat, urine of immunocompromised patients.

36. Isolation
• Viral isolation in cell culture requires human cells.
• Human epithelial cell lines such as Hep-2, HeLa and BK are sensitive
but difficult to maintain.
• Primary monkey kidneV cells will permittee growth and isolation of
AdV 40 and AdV41 strains.
• Isolates grown in these cells are identified by noting cytopathic effects
or by immunofluorescence staining using anti hexon antibody ,
heamagglutination inhibition test and neutralization test.
• Shell vial techniques can also be employed for isolation of the virus.
• Can also be detected by electron microscopy, ELISA or by latex
agglutination tests.

37. Serology
• Paired sera should be used to detect rise in antibody titre.
• Antibodies in patients sera can be detected by ELISA,
complement fixatation test, heamagglutination inhibition and
neutralization test.
Molecular techniques:
• PCR, restriction endonuclease digestion, DNA hybridization.
Treatment: no specific treatment

38. ADENOVIRUS
TREATMENT
Antivirals againstAdV:
 Potential targets:
 AdV DNA polymerase
 AdV cysteine protease
 receptors for binding host cells
 Antivirals in use:
 Ribavirin
 Cidofovir
 Ganciclovir
 (Vidarabine)

39. PREVENTION AND
CONTROL
Careful hand washing is the easiest way to prevent infection.
Disinfection of Environmental surfaces with hypochlorite's.
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.

40. •PREVENTION OF ADENOVIRAL
INFECTIONS
• Prevention:
• Vaccines were developed for adenovirus serotypes 4 and 7, but were available only for
preventing among military
• recruits.
• Strict attention to good infection-control practices 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.

41. EPIDEMIOL
OGY
• Worldwide in humans as well as in a variety of animals.
• Human Adenovirus are generally not pathogenic to animals and animal
adenoviruses are pathogenic within the species .
• Infection varies from sporadic to epidemic
• Pattern often correlates with the viral serotypes and the age of the
susceptible population
• Fecal oral transmission accounts for infections in young children.
• Initial spread by respiratory route
• Prolonged carriage in the intestine makes the feces a more common source
• The reservoir for adenovirus is in humans.
• Adenoviruses have a worldwide distribution, and they are ubiquitous in the
environment where contamination of human feces or sewage has occurred.

42. • Infections can occur throughout the year.
• Outbreaks have been more common in late winter, spring, and early
summer.
• Though most adenovirus infections are mild, fatality and a number of
sequelae are associated with immunocompromised patients.
• Adenovirus is a very common infection, estimated to be responsible for
between 2% and 5% of all respiratory infections.
• All ages are susceptible to adenovirus infection, but infection usually
occurs during childhood.
• Acute lower respiratory tract infection in children is a major worldwide
health problem, and the virus is second only to rotavirus in terms of its
significance as a cause of childhood gastroenteritis.
• In the winter, adenovirus has caused many cases of illness in military
recruits, with about 25% requiring hospitalization for fever and lower
respiratory tract disease. Some cases result in death.