” ADENOVIRUS
1. what is Adenovirus?
Adenovirus is found to
be naked with an icosahedral appearance. It was first discovered in 1953 by
Rowe and his colleagues. As it is isolated from adenoids cell culture it is
termed as adenovirus. It is known to be the cause of acute respiratory tract
infections, pneumonia it is also reported in case with acute follicular
conjunctivitis epidemic kerato conjunctivitis, cystitis, and gastroenteritis (
occasionally ). Not only it affects adults but also it is normally seen in
children. Adenovirus UTI is common in males. In infants , pharyngitis and
pharyngeal – conjunctiva fever are the common infections. More than 100
antigenic types of adenovirus have been identified that infect mammals ( mast
adenoviruses ) and birds ( avid
adenoviruses ); 47 human adenovirus types are classified , 5 more viral types
are presently studied. Moreover, 70% of mortality is found to be reported in
immunocompromised cases.
Structure:
Adenovirus
is a double stranded DNA virus. It is icosahedral symmetry measuring with 80nm
in diameter ( 70 to 100nm ). Its capsid consist of 252 capsomeres ( 240 hexons, 12 pentons ). Pentons
make up the apices and possess projecting fibers. The fibres enable them to be
involved in hem agglutination process
and mediate the attachment of the virus to cellular receptors at least 47
serotypes of human adenovirus are known and they are classified into 6
subgenera ( A to F ) on the basics of oncogenicity on newborn hamsters and
nucleotide sequence homology. The hexon contains family – reactive
determinates; type – specific determinants are present on the pentons and
hexons.
Genome:
The
Adenovirus genome is linear, non-segmented double-stranded ( ds ) DNA that is
between 26 and 48Kbp.
Adenoviral genome
encoded with 22 to 40 genes.
The 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.
Pathogenesis:
Source
Infected aerosol
Healthy carrier
–adenoids
Tonsils
containing virus can be shaded and spread the infections.
Mode of
transmission – Direct inoculation in to
conjunctiva-conjunctivitis.
Faeco oral route –
gastrointestinal complication.
Inhalation of airborne
droplets for respiratory illness.
Life cycle of
virus :
Adenoviruses possess a
linear dsDNA genome and are able to replicate in the nucleus of vertebrate
cells using the host’s replication machinery.
In viral
multiplication, there is an interaction takes place in between the virus and
the host and cell.
At first virus gets
attached on host and its entry is favored by CAR (coxackie adenovirus
receptor).
Moreover integrin (av
integrin) molecule helps to medicate the entry of the adenovirus by
clathrin-coated endocytosis (endosomes). During endocytosis a vesicle like
structure is formed inside the host in which viral particles is seen this is
called endosome.
Once the virus has
successfully entered into the host cell, the endosome is getting acidified,
which alters the capsid of virus these changes would favors to facilitate the
endosome to be destroyed thereby virion is released, this virion is moved
towards the cytoplasm with the help of cellular microtubules, then
virion releases the adenovirus particle.
Then viral DNA with 55
KD proteins enter the host nucleus via the nuclear pore. Then start to
synthesis early mRNA which results in synthesis of protein E1. E1 and then
induces to produce E4/E3 which are important in replication. However in this
replication, upper strand acts as template for synthesis new strand with this
regard DNA polymerase bind along with 80 kd
protein thereby new strands can be generated and followed by pan
handle DNA formed. After, second stage of replication is started using E4
proteins to have been made DNA with 55kd proteins once it is formed then start
to synthesis late m RNA
The late phase of the
adenovirus lifecycle is focused on producing sufficient quantities of
structural proteins like pentose hexose to be packed in nucleus thus capsid
developed using these proteins and passed into ER and Golgi apparatus.
Once the viral
components have successfully been replicated, progeny virus is developed and
released from the cell as a result of virally induced cell lysis.
Respiratory
Disease in children:
Laryngo tracheobronchitis
: it
is the most important Adenovirus infected seen in 5%of children under
the age of 4 years; also it occurs in 10%of hospitalized respiratory infection
cases in this age group. Pneumonia in young children is the most serious
manifestation.
Pharyngoconjunctival
Fever: This disease is characterized by conjunctivitis,
fever, pharyngitis and adenoidal enlargements.
Acute
Respiratory Disease ( ARD )in Military Recruits : It
develops with Characteristic symptoms of fever, malaise, sore throat,
hoarseness and cough. Pneumonia develops in around 10% of cases.
Pertussis: Adenoviruses
can be isolated frequently ( 39%)of patients infected with B. Pertussis.
Acute following
conjunctivitis : this is part of the syndrome of
pharyngoconjunctival fever. This syndrome is characterized by an aggressive
conjunctivitis, pain, photophobia and lymphadenopathy followed by the
development of superficial punctate keratitis.
Acute Hemorrhagic
Cystitis: This syndrome occurs predominantly in 6 to 15 year
old boys. The syndrome consists of acute dysuria with hematuria and is mainly
associated with Ad 11. It is causing serious diseases in the kidney such as
glomerulonephritis.
Meningitis : Adenoviruses
Ad3 and Ad7 may be infrequent cause of meningitis.
Host Defenses :
Most adolescents and adults have circulating neutralizing antibodies; immunity
is wide spread. Cytotoxic T lymphocytes destroy adenovirus-infected cells.
Epidemiology : Adenovirus infections are widely distributed in human populations.
The highest susceptibility is found among children from 6 months to 2 years of
age and extends to the group of 5 to 9 year old children. Types 2, 1,3,5,7, and
6 (in that order ) are most frequently isolated from adenovirus-infected
children. Adenovirus infections are responsible for only 2 to 5 percent of
acute respiratory infections in children. However, Adenovirus types 4, 7, and 3
can cause acute respiratory diseases, including pneumonia, in this age group.
Adenoviruses ( type 42
to 47 ) have been isolated from severely
immune compromised patients, such as those with acquired immune
deficiency syndrome( AIDS).
Diagnosis: infection
with an adenovirus may be suspected on the basis of a characteristic clinical
presentation e.g., respiratory disease, conjunctivitis the diagnosis can be
confirmed by demonstrating a rise in antibody titer between acute-phase and
convalescent- phase sera or by virus detection or isolation. In serology,
complement fixation, ELISAs serum neutralization and HAI methods are employed.
Control : treatment is not properly available to
control this viral infection. Nevertheless vaccines, including recombinant
vaccines, are being employed. Whole - virus cannot be used as vaccines since it
has been the potential risk of oncogenesis.
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