ADENOVIRUS

INTRO/HX

These viruses were named "adenovirus" because they were first isolated in 1953, by Wallace Rowe, from tissue
cultures of human adenoidal tissue.
After co-culturing the infected tonsilar and adenoid tissue with other cells, there was a characteristic cytopathic
effect [CPE] and isolation of a virus, later called Adenovirus

These viruses are clinically impt becos of their capacity to [i] cause acute infections of the R.S. and conjunctiva,
[ii] cause tumor in animals and [iii] interact with other animal viruses such as Siman virus 40 to form hybrid
viruses with unique biologic properties

Adenovirus is ubiquitous in human and animal populations, survives long periods outside a host, and is endemic
throughout the year.

HUMAN ADENOVIRUS VS ANIMAL ADENOVIRUS

They all:

Share cross-reacting, group-specific Antigens except the avian adenovirus

Have Similar morphology
Have Nucleic acid composition
Have Xteristic CPE (cytopathic effect) in susceptible cells

However, animal adenoviruses have not yet been isolated as the causative agents of human diseases.

CLASSIFICATION

Adenoviruses belong to family Adenoviridae, genus Mastadenovirus [mainly]

They are further classified into 6 subgroups (A through F), based on hemagglutinating properties and
DNA homology.

About 47 serotypes have been isolated from humans.

Common serotypes are 1-8, 11, 21, 35, 37, and 40.

SUBGROUPS SEROTYPES COMMENTS

A 12, 18, 31 Sarcoma in rodents
B 3, 7, 11, 14, 16, 21, 34, 35, 50, 55 Resp dx = HAdV B and C
C 1, 2, 5, 6,
D 8, 9, 10, 13, 15, 17, 19, 20, 22, 23, 24, 25, 26, 27, Conjunctivitis = HAdV-B and D
28, 29, 30, 32, 33, 36, 37, 38, 39, 42, 43, 44, 45,
46, 47,
E 4
F 40, 41 Gastroenteritis

PROPERTIES
Adenoviruses are stable in the environment and to low pH, bile, and proteolytic enzymes - These properties
make it possible for them to replicate to high titers in the GI tract.
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STRUCTURE OF ADENOVIRUSES

Genome = linear [non-helical] dsDNA that replicates asymmetrically

Capsid = 252 capsomeres arranged in an icosahedral symmetry of 20 sides & 12 vertices.
o 240 of the capsomere are HEXONS
These have group-specific and type-specific antigenicity
o 12 are PENTONS @ the 12 vertices from which FIRBRES project with their terminal
knob domain
The penton based antigens is common to the entire adenovirus family
The Fibre antigens are Primarily type-specific with some group-specificity
They are the organ of attachment and is a hemagglutinin
They also determine target cell specificity
o These 3 components are morphologically and immunologically different, and they are
toxic to cells - causing rounding and death of cells through inhibition of DNA, mRNA
and protein synthesis.

Group-specific (gs) antigen = common to a certain group of organisms e.g. streptococci,

oncornaviruses
Type-specific (ts) antigen = specific for a particular species of an organism

Neutralizing antibodies produced against the hAdV are hexon type-specific and lifelong

Core proteins: Major, Minor & Hexon-associated proteins

NO envelop = Naked

TRANSMISSION:

[1] Aerosol droplet, [2] Fecal-oral route and [3] direct inoculation of conjunctiva by tonometers or fingers.
The fecal-oral route is the most common among young children and their families

EPIDEMIOLOGY

Endemic, epidemic and sporadic infections occur. Its endemic worldwide

Outbreaks occur among military recruits (apparently as a result of close living conditions that
facilitate transmission), swimming pool users, residential institutions, hospitals, day care centers etc.
Infections are most communicable in the first few days of illness, however infective period continues
since clinical infection may be followed by intermittent and prolonged rectal shedding of the AdV (for
months to years)
o Approximately 50% of infants have faecal shedding of adenoviruses.
Adenovrius outbreaks are seasonal: Respiratory disease mainly occurs in late winter through early
summer. Pharyngoconjunctival and EKC infections occur in the summer months while GI disease
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does not seem to be seasonal

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PATHOGENESIS AND REPLICATION

The Primary hAdV infection usu. take place in the first few years of life & by the end of the first decade of life,
most of the populations have experienced infection with one or more serotypes.

The Virus primarily attacks mucoepithelial cells of the conjunctiva, respiratory tract, gastrointestinal and
genitourinary tracts, causing desquamation
They also attack & replicate in associated lymphoid tissues (i.e. those in close proximity to the desquamated
tissue), making the lymphoid tissue hypertrophic with an active germinal centre; and subsequent viremia can
cause secondary infection in visceral organs.

Attachment & Entry of the virus into the host cell:

PRIMARY INTERACTION of knob domain of the fibre protein with 2 established receptors on the
host cell: CD46 (for all hAdV-B, Except 3 and 7 serotypes) and coxsackievirus adenovirus receptor
CAR (for all Other serotypes)
o CD46, which is expressed virtually in all cells of the host, acts as a co-factor for inactivation
of the complement C3b
o CAR is present in tight jxns of polarized cells where it mediates cell to cell adhesion
SECONDARY INTERACTION of pentose protein with v Integrin (v3 and v5) of host cell,
a co-receptor interaction that stimulates entry of the adenovirus via endocytosis

In the host cell, the life-cycle of the AdV begin consisting of DNA replication process that separates 2 phases:
an early and a late phase. The late phase is followed by assembly and release of virions.
The viral DNA replicates in the nucleus but the rest of the virus replicates in the cytoplasm

In Early phase, early mRNAs are produced for translation into Regulatory Proteins for the
following fxns:
o to alter the expression of host proteins that are necessary for DNA synthesis
o to activate other virus genes (such as the virus-encoded DNA polymerase,)
o to avoid premature death of the infected cell by the host-immune defenses (blockage
of apoptosis, blockage of interferon activity, and blockage of MHC class I translocation and
expression).
All these fxns are focused on ensuring unhindered viral DNA replication in the nucleus
In the late phase, structural proteins, to pack all the genetic material produced by DNA replication,
are produced (from late mRNA)
Next, assembly and release of virus from the host cell as a result of virally induced cell lysis

Three types of infections occur in target cells:

Lytic infection - cell death occurs as a result of virus infection of the mucoepithelial cells with the
release of abt 104 to 106 progeny particles per cell of which 1-5% are infectious.
Latent / persistent / occult infection - In this regard the AdV resemble Herpes viruses. Virus
remains in the host cell, which is not killed (lymphoid tissues such as tonsils, adenoids, Peyers patches),
During this infection, only a small no. of viruses may be release and, usually, cell death outstrips cell
multiplication thereby resulting in apparent infection.
Oncogenic transformation host cell growth and replication (as well as viral DNA replication)
continue without death of the host cell. As a result, no infectious virion is released. This is seen in
hamsters, most often with group A viruses.

Inefficient (error-prone) replication of the virus results in many excess antigenic components. These are liberated
into the culture fluid in vitro as soluble antigens and lead to formation of basophilic staining intra-nuclear inclusion
bodies in cells.

ORGANS AFFECTED BY ADENOVIRUS INFECTION

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MAJOR ORGANS: R.S, eye, G.U.T and GIT (including liver)

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MINOR ORGANS: Pancreas, myocardium, CNS

CLINICAL SYNDROMES see table below

THINGS TO NOTE:

Approximately of all adenovirus infections are asymptomatic or subclinical.

Most of the symptomatic infections resolve spontaneously (i.e. most are self-limiting)
Also, most infections induce type-specific immunity
The incubation period is 12-14 days; for conjunctivitis usu. 6-9 days; for gastroenteritis, 3-10 days.
Serotypes 1, 2, 5, 6 are seen commonly in young children
Serotypes 3 & 7 are more freq. isolated from young adults with acute URI and acute LRI. They are also
found in military recruits
Serotypes 8 & 19 freq. isolated from ocular infection in adults
For Acute haemorrhagic cystitis: boys are more affected than girls. However, the reverse is true of
bacterial cystitis. To differentiate it from Glomerulonephritis (GN): GN has hypertension as a feature
which is not seen in A.H. Cystitis. Also, test for excretory and concentrating fxns of the kidney are
normal for AHC but not for GN
Coeliac dxs is a common autoimmune dx thought to be caused by ingestion of protein of Wheat,
Bailey or Rye. This proteins include gliadin A, horderin and Secalin
There is a structural homology btw gliadin A and E13-55-1a protein of AdV (esp type 12)
o T-lymphocytes from pxs with coeliac dx recognize a synthetic decapeptide that is shared by
AdV-12 protein and gliadin A
AdV infection in pregnancy causes persistence/latency
o Replication competent adenovirus genome remain tonsils, adenoid and intestine of infants

ORGANS CLINICAL FEATURES SEROTYPES

SYNDROME
Resp. tract 5% of URI Coryza, pharyngitis, tonsillitis, fever 1, 2, 3, 5, 6, 7
10% of LRI Bronchitis, atypical pneumonia, fever, 3, 4, 7, 21
cough
Pertussis like Fever, paroxysmal cough, post- 5
syndrome tussive vomiting
Eye Pharyngo-conjuctival Fever, conjunctivits, pharyngitis, 3, 4, 7, 14
fever headache, rash, lymphadenopathy
Acute Bulbar and palpebral conjunctivitis, 11, 21
follicular/Hemorrhagic Chemosis, follicles, subconjunctival
conjunctivitis hemorrhage, preauricular
lymphadenopathy
Epidemic conjunctivitis Headache, conjunctivitis followed by 8, 19, 37
keratitis, preauricular
lymphadenopathy
Genitourinary Acute Hemorrhagic Macroscopic hematuria of 3 days 4, 7, 11, (1,
cystitis duration), fever, 21)
Microscopic hematuria, dysuria and
urinary freq. may persist much longer
than 3 days
OTHERS: orchitis,
nephritis, oculogenital
syndrome
Gastro- Gastroenteritis Infantile non-bloody diarrhea (< 40 & 41 (42,
intestinal 4yrs), low-grade fever 31, 25-28)
Intussusception 1, 2, 5 6
Some hyper-irritability But NO INFECTION
that may cause
intussuscept.
Coeliac dx Alternating constipation and 12
diarrhoea
Hepatitis, Appendicitis

Pancreas Pancreatitis
heart Myocarditis, Pericarditis
4

CNS Meningitis, encephalitis

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