Adenovirus

introduction image

Adenovirus is a type of DNA virus, which are medium-sized, non-enveloped and double-stranded. Adenovirus named after its isolation from the human adenoid tissue. It was first introduced by a scientist named Rowe who cultured and isolated adenovirus by the plasma tissue culturing. This group of virus can infect human, animals and birds. Adenovirus can cause various diseases like respiratory tract infection, lung infections, common-cold, conjunctivitis etc.

Adenovirus is ubiquitous, which can spread worldwide. The life cycle of adenovirus is a very complex process which first infects the cell, replicates and multiply within the host cell and finally release to produce various types of infections. The infections of adenovirus are most likely to occur in the late winter, spring and early summer months. It is most prevalent in children between the age group of 6 months to 2 years than adults.

Content: Adenovirus

  1. Definition of Adenovirus
  2. Structure
  3. Genome Organisation
  4. Classification
  5. Epidemiology
  6. Pathogenicity
  7. Diagnosis
  8. Adeno-Associated Virus

Definition of Adenovirus

Adenovirus can define as the virus which belongs to the group-1, ds-DNA human virus, which can usually cause acute respiratory infections and occasionally cause conjunctivitis, cystitis and gastroenteritis. It was first isolated after culturing the human adenoid tissue in the plasma tissue culture, and hence it is named as “Adenovirus”. It belongs to the family of “Adenoviridae” and subdivides into two genera namely:

  • Mastadenovirus: It is the mammalian adenovirus, i.e. cause infections in mammals.
  • Aviadenovirus: It is the avian adenovirus, i.e. cause infections in aves.

Resistance: Adenovirus is relatively stable virus particles which can survive at a temperature of 37degrees Celsius for about a week. It gets inactivated at a temperature of 50degrees Celsius or above. It also shows resistance towards chemical agents like ether and bile salts.

Host range: Adenovirus can infect mammals and birds and are “Host-specific”. It can attack rapidly to the human embryonic kidney, HeLa/HEp-2 cells.

Structure

The size of adenovirus is larger than the other viruses, but its structure is quite simple, and it shows the following structural properties:

structure of adenovirus

Size: It is medium-sized.

Shape: Shows “Icosahedral symmetry” and resembles to the shape of the space vehicle.

Capsid: The adenovirus has an icosahedral, naked and non-enveloped capsid. The diameter of the capsid ranges from 90-100 nm. There are 252 protein subunits of a capsid, which refers as “Capsomeres”.

The capsomeres consist of 240 hexon subunits and 12 penton subunits. The 240 hexon occupies the faces, and 12 pentons occupy the vertices of the capsid or shell.

Pentons consists of penton base and penton fibre. A long penton fibre attaches to the penton base acts as “Hemagglutinin” and carry specific antigens, which are toxic to the cells. Knob like structure is present to the terminal ends of the penton fibres which helps in attachment of the virus to the host cell.

Core: The core of adenovirus consists of a linear, ds-DNA genome and composed of protein V, VII and arginine-rich protein (µ). Inside the core of adenovirus, a protein of 55KDa attaches to the 5’end of the ds-DNA.

Genome Organisation

The genome organisation of adenovirus consists of linear, non-segmented and ds-DNA with a size of 30-38 Kb. Its genome produces four types of gene products during the gene expression.

genome organization

E1A is a gene product of the immediate-early phase of gene expression. Gene products, namely E1B, E2A, E2B, E3 and E4, produces during the early stage of gene expression. VA is an intermediate gene product which encodes small RNAs (VA1 and VA2 RNAs) and produces during the intermediate stage of gene expression. Gene products, namely L1, L2, L3, L4 and L5, MLP and Ψ gene produces during the late phase of gene expression.

  • Immediate early genes help in the replication of viral DNA.
  • The early genes modulate the immune response of the infected cells and help in the viral DNA replication and transcription of late genes.
  • An intermediate gene helps in the regulation of translating mRNAs.
  • The late genes help in the synthesis of structural components at the time of virus biosynthesis and assembly.

The genome of adenovirus also encodes tripartite RNA leader or TPL sequences. Later, the TPL sequences are spliced up by the viral genome, onto all the late viral mRNAs. Both the strands of DNA codes the specific genes, which perform distinct functions. Its genome also carries inverted terminal repeat sequences due to which the denatured single strands transform into circular or panhandle DNA molecule. To each 5’ end of viral DNA, a protein of molecular weight 55KD is covalently attached.

Phase of gene expressionGene products of AdenovirusFunctional role
Immediate early phaseE1ABinds with the human pRb and prevents from the cell cycle arrest
Early phaseE1BBinds with the human polypeptide-53 and prevents apoptosis mediated by p-53
E2AHelps in adenovirus replication
E2BHelps in viral polymerization
E3Removes CD95 from the from the cell surface and prevents TNF (Tumor Necrosis Factor) dependent apoptosis
E4Helps in replication of adenovirus
Intermediate phaseVA (VA1 and VA2 RNAs)Helps in regulation of translating mRNAs
Late phaseL3Cleaves viral precursor proteins
L4Helps in the viral replication
L1Encodes capsid protein (p3a) which helps in the biosynthesis of capsid
L2Helps in DNA packaging and DNA condensation
L5It is also a capsid protein which encodes p-7 gene
ΨIt is a sequence which give signals at the time of viral packaging
Major late promoter (MLP)Controls or promotes all the late phase genes
-LITR and RITRLeft inverted terminal repeat and Right inverted terminal repeat sequences contains origin of replication

Classification

There are about 100 antigenic types of mammals and birds adenovirus. From the 100 antigenic types, about 50 serotypes of adenovirus have been identified from the human sources.

The human adenovirus divides into six groups, based on the properties like haemagglutination, fibre length, oncogenic potential etc.
Let us study the six serotypes of human, which also refers to as “Subgroup or Subgenus”.

Group (Subgenus)SerotypesHaemagglutinationOncogenic potential (Tumourogenicity)
A12, 18, 31+/- (Partial haemagglutination)High
B3, 7, 11, 14, 16, 21, 34, 35+ (Complete haemagglutination)Weak
C1, 2, 5, 6+/- (Partial haemagglutination)-
D8, 10, 13, 15, 17, 19, 20, 22, 30, 32,33, 36, 39, 42, 47+ (Complete haemagglutination)-
E4+/- (Partial haemagglutination)-
F40, 41+/- (Partial haemagglutination)Not known

Some of the human serotypes have been identified and isolated from the patients concurred with AIDs. In adenovirus, group-specific antigens are present on the hexon whereas type-specific antigens are present on penton base and fibres. An immunological neutralization test can help us to study the serotypes of adenovirus.

Epidemiology

Epidemiology of adenovirus can be studied by knowing all the factors that are related to the virus which can cause pathogenicity in the host cell.

Reservoir or carrier: Human and non-human primates (Monkeys) are the primary reservoirs.

Transmission: Adenovirus is commonly transmitted from person to person, through respiratory droplets and sometimes by sharing personal items and through contaminated water.

Clinical illness: It can cause fever, which can last for 3-5 days, atypical pneumonia, respiratory tract infection, tracheitis, bronchiolitis etc.

Risk factors: Children and infants are mainly get affected by adenovirus. Children are usually infected with mild pharyngitis or tracheitis.  Infants are usually infected with fulminant bronchiolitis and pneumonia.

Pathogenicity

Adenovirus can cause the following pathogenic diseases:

Pharyngitis

It is a type of upper respiratory tract infection which are caused by viral serotypes 1-7.  It is the clinical condition which causes inflammation of the pharynx. Pharyngitis includes symptoms like:

  • Sore throat
  • Runny nose
  • Fever
  • Cough
  • Headache

The symptoms of pharyngitis can last for 3-5 days and it includes complications like sinusitis and otitis.

 Pneumonia

Serotypes 3 and 7 are associated with causing pneumonia in adults. Type 7 of adenovirus can cause serious illness in infants and young children. It is the clinical condition which causes inflammation in the lungs and also affects alveoli. Pneumonia includes symptoms like:

  • Dry cough
  • Chest pain
  • Fever
  • Difficulty in breathing
  • Release of sputum
  • Blue tinged eye
  • Convulsions

Pneumonia can last for a few weeks to months and includes complications like Asthma, diabetes, heart failure etc. It is also a type of upper respiratory tract infection.

Acute respiratory diseases

Mostly occurs as outbreaks in military recruits and caused by the serotypes 4, 7 and 21. It is a clinical condition which infects the nose, trachea and lungs by causing tracheitis, bronchiolitis. Acute respiratory infections obstruct normal breathing functions. It includes symptoms like:

  • Congestion
  • Runny nose
  • Cough
  • Sore throat
  • Fatigue
  • Dizziness
  • Difficulty in breathing

Acute respiratory infections include complications like respiratory arrest, respiratory failure and congestive heart failure.

Pharyngoconjunctivital fever

Serotypes 3, 7 and 14 are likely to cause febrile pharyngitis and conjunctivitis in the civilian population. Pharyngoconjunctivital fever (PCF) is an acute and highly infectious viral disease of the conjunctiva which leads to cause fever, pharyngitis and an acute follicular conjunctivitis.

Epidemic keratoconjunctivitis

It is most usually caused by serotype 8 and types 19 and 37 are also involved sometimes. It is the clinical condition which causes inflammation of the cornea and conjunctiva. Epidemic keratoconjunctivitis is highly contagious which includes symptoms like:

  • Swollen lymph nodes
  • Fever
  • Headache
  • Fatigue
  • Redness in the eyes
  • Itchiness and irritation in the eyes
  • Conjunctivital edema
  • Excessive tearing
  • Release of yellow discharge from the eyes

Acute follicular conjunctivitis

For this, serotypes 3, 4 and 11 are mainly responsible, which cause inflammation of the conjunctiva, enlargement of submucous lymphoid follicles and preauricular lymph nodes.

Gastroenteritis

Serotypes 40 and 41 have been isolated from the faeces and designated as “Enteric type adenovirus”, can cause infantile gastroenteritis. Gastroenteritis occasionally occurs, which causes inflammation of the intestinal lining and can be identified by the stool ELISA test.

Diagnosis

Through the following methods, we can diagnose the pathogenicity of adenovirus:

Tissue culture: For this first, collect the adenovirus from the throat, eye, urine, faeces etc. of the infected person. Then, inoculate the sample in the tissue culture and incubate it for desired temperature and time period. The identification of an organism is possible by:

  • Observing the cytopathic effects
  • By performing the complement fixation test
  • By performing neutralization test

Electron microscopy also helps in the identification and diagnosis of enteric type adenoviruses. Immunoassay techniques like Fluorescent antibody test and ELISA also helps in the diagnosis. PCR based test also helps in the detection of viral DNA.

Adeno-Associated Virus

Adeno-associated viruses (AAVs) are another group, which also refers as Adeno-satellite virus. AAVs depends on the adenovirus for their replication and belongs to the family of Parpoviridae. AAVs are also classified as “Dependovirus”. These can be identified by the electron microscopy, complement fixation or immunofluorescence method. Its pathogenicity is still unknown.

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