Adenovirus

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 keratoconjunctivitis, 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 symmentry measuring with 80nm in diameter ( 70 to 100nm ). Its capsid consist of252 capso  meres ( 240 hexons, 12 pentons ). Pentons make up the apices and possess projecting fibers. The fibres enable them to be involved in hemagglutination  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 shedded 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 endsome 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 ir 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 pentoses 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:

Laryngotracheobronchitis : 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.