adeno viurs

8/14/2019 Adeno viurs

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Introduction:

Adenoviruses are the group of viruses infecting adenoid tissues and the cause of upper

respiratory tract infections and cold. They have been isolated from every species of animals

such as birds, mammals and amphibians. They can also cause diseases in gastrointestinal and

urinary tracks and the eye.

The adenoviruses were first isolated by Rowe et al in 1953 from the adenoidal tissues

of the tonsils of the children. In 1954 Hillema isolated a related virus from throat washing of

a military recruit with acute respiratory track illness.

The recent evidence of adenovirus causing obesity in mammals and animals was

reported by Leaho Whigham published in American journal of physiology regulatory,

integral and comparative physiology published by the American physiology society. Ad 37b

causes obesity in chicken, Ad36 and Ad 5 causes obesity in animals and Ad 36 has been

responsible for human obesity.

There are nearly 51 distinct antigenic types have been isolated from humans

responsible for infection. A few types serve as model for cancer inducing in animals.

Classification:

Adenovirus has been classified under the family Adenoviride. The main genera are

Mastadenovirus related to humans, Adviadenoviruses related to birds, Ataadenoviruses

related to reptiles, ruminants, birds, brush-tail possum, Siadenovirus related to frogs and birds

and Ichtadenovirus related to fish. Human adenoviruses are divided into 6 groups from A to

F based on their physical, chemical and biological properties. Adenoviruses have given group

have fibres of characteristic length display considerable DNA homology. The G+C content of

DNA potentially can produce tumors in new born rodents.


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Morphology:

Adenoviruses are 60-90 mm in diameter, composed of 252 capsomers consisting 240

hexons and 12 pentons at vertices of icosohedron. The hexon consists of trimmer polypeptide

II with a central pore VI and VIII and IX are minor polypeptides associated with hexons

involved in stabilization or assembling. The penton base consists of pentarmers of peptide III,

5 molecules of 3A or also associated with it. The pentons have toxin like activity in the

absence of other virus components. A Trimmeric fibre protein extends from each 12 vertices

presented at the base responsible for binding cellular proteins. The genome is linear double

stranded 24-45 Kbp, having 30-40 genes. The terminal sequence of each strands are inverted

repeats. Hence denatured structures can form Panhandle structure (100-140 bp). This one of

the criterion to classify the group; where if the homology is 70-95% it is with in the group

and if the homology is 5-20% it is between the group.

Replication:

The virus attaches to the cell via fibre structure. The receptors of host cell are called

Coxsackie Adeno Receptor (CAR) molecule, belonging to the immunoglobulin gene family

and MHC-1. The virus interacts with cellular integrins followed by attachment. There are two

steps in this process; adsorption and internalization.

The adsorbed virus is internalized into endosome from which majority of particles

enter into cytosol by a process triggered by acidic pH of the endosome. Uncoating takes place

with the release of pentons. The pentons release the spherical uncoated particles which

contain the viral DNA into the cytoplasm. The core migrates into the nucleus through the

nuclearpore, where it is converted into a virus DNA cell histone complex.

The replication consists of early and late events. The goal of early event is to induce

host cell to enter S phase of cell cycle, to create condition favourable for viral replication

and to protect viral cell from host defense mechanism. This process is also required to

synthesize viral gene product needed for DNA replication. There are four important genes

involved in the whole process. They are E1, E2, E3 & E4.

The E1A gene is necessary for the transcription of early regions of the virus.

Modulation of early cell cycle is accomplished by the gene product. The E1B gene blocks a

protein that causes cell death (apoptosis) that occur due to E1A function. Since the pre mature

death of the cell can affect the virus yield.E2A and E2B genes provide machinery for thereplication of DNA of the virus. The E3gene produces Adenovirus Death Protein (ADP)

which helps in cytolysis, which releases the viral progeny efficiently. The E4 gene mainlyfacilitates viruses mRNA metabolism and provides functions to promote virus DNA

replication there by switching off the host protein synthesis


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Latent event recognizes with the viral DNA synthesis. The late (L) promoters control

expression of gens coding for viral structure protein. There are 18 different mRNA are

produced on splicing the primary trancript which are grouped under L1 to L5 based on their

function. The processed transcripts are transported to the cytoplasm where viral proteins are

synthesized. Along with these a few genetic sequences are also transported to the cytoplasm.The complexes, E1B 55kDa polypeptide and E4 34-kDa polypeptide inhibits cytoplasmic

accumulation of cellular mRNA and induces viral mRNA synthesis. Large amount of viral

structures are produced in the cell.

Viral assembly and Maturation:

A late L4 encoded scaffold protein assists the aggregation of hexon polypeptides.

Capsomers get assembled into empty shell capsid in nucleus. The DNA enters preformed

capsids. Cis acting DNA element near the left hand end of the viral chromosome serves as a

packing signal necessary for encapsidation. The L1 protein facilitates DNA encapsidation. It

takes 20- 24 hours for the infectious lifecycle. About 100000 virus particles are produced per

cell, yet 90% viral DNA and 80% of hexons capsomers are not used.

Effect on host defense Mechanism:

The virus incorporates several anti viral components from the cell to defend it self

against the host. The VA RNAs the non translated RNA transcribed by the virus, prevent the

activation of the eukaryotic initiation factor 2 there by combating cellular defense. The E3

exhibits cytolysis of infected cell there by releasing the virus. E3 groupp19-kDa blocks

movement of MHC class I antigen to cell surface protecting virus from cytotoxic T-

Lymphocytes mediated lysis.

Effect on cell:

The virus is cytopathic for human cells specially kidney and continuous epithelial

cells. It causes rounding or enlargement and aggregation of affected cells into grape like

clusters without being lysed. They exhibit crystalline arrangements in the cell.

Pathogenicity:

The Adenoviruses are mainly responsible for the respiratory tract, the gastrointestinal

tract and eye infection. They replicate in epithelial cells of the respiratory tract the

gastrointestinal tract, eye, urinary bladder and liver. They are restricted to the lymph nodes

and do not spread to the other parts of the body. Most of them replicate in the intestinal

epithelium.


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Clinical findings:

About one third of the known human serotypes are associated with human illness. A

single serotype may exhibit different clinical symptoms. Adenoviruses 1-7 are most

commonly type found world wide. They are responsible for the major adenovirus associated

illness.Adenoviruses associated clinical syndromes and the serotypes are listed below.

1. Pharyngitis 1, 2, 3, 5, 7

2. Pharyngoconjunctival fever 3, 7

3. Acute respiratory disease of recruits 4, 7, 14, 21

4. Pneumonia 1, 2, 3, 7

5. Follicular conjunctivitis 3, 4, 11

6. Epidemic keratoconjunctivitis 8, 19, 37

7. Petussis-like syndrome 5

8. Acute haemorrhaghic cystitis 11, 21

9. Acute infantile gastroenteritis 40, 41

10. Intussusception 1, 2, 5

11. Severe disease in AIDS and other immunocompromized patients 5, 34, 35

12. Meningitis 3, 7

Respiratory disease:

The symptoms include cough, nasal congestion, fever and sore throat. This is mostly

caused by group C virus in children and infants. The types 1,2,5,6 are responsible for 10-2%

of childhood pneumonia. The mortality rate is found to be around 8-10%.

Acute respiratory disease in military recruits belong to the serotype 4,7,21,14 and 3

occasionally cause sore throat, fever nasal congestion, cough, malaise leading to pneumonia.

This usually happens among the newly enlisted troops.

Eye infection:

Acute follicular conjunctivitis or mild ocular involvement is part of the respiratory

pharyngeal. Pharyngoconjunctival fever occurs in out breaks such as children in summer

camps. The type associated is 3and7. It may last for 1-2 weeks.

Epidemic keratoconjunctivitis is a serious disease which is contagious in adults.

Adenovirus causing this disease remains viable in towel and sinks for many days. This is the

main source of transmission. The disease is characterized by conjunctivitis followed by

keartitis. It is usually resolved in 2 weeks. It may cause sub epithelial opacities in the corona

up to 2 years. The types involved are 8, 19 & 37


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Gastrointestinal disease:

The Adenovirus replicate in intestinal cells is a sign of systemic infection. They may

cause both respiratory illness and diarrhea in children with high fever. The types are 40 & 41

abundantly present in diarrheal stools. They are very difficult to cultivate.Pharyngoconjunctival fever:

The disease is characterized by conjunctivitis, fever, pharyngnitis and adenoidal

enlargement. This is frequently associated with swimming pools. Adequate level of chlorine

can inhibit its out break.

Diseases in Immunocompromised patients:

In transplant patients it causes respiratory disease that may progress to pneumonia and

may be fatal. Children receiving liver transplants may develop adenovirus hepatitis in the

allograft. Children receiving heart transplants may develop myocardial infections at increased

risk of graft losses. Patients with Acquired Immunodeficiency Syndrome suffer from

adenovirus infection of the intestinal tract. Bone marrow transplant recipients are vulnerable

for all DNA viruses.

LAB diagnosis:

Depending on the clinical disease virus may be recovered from stool, urine, throat

conjunctival and rectal swabs. 1-3 days for adults with cold, 3-5 days forpharyngoconjunctival rever, 2 weeks for keratoconjunctivitis, 3-6 weeks for children with

respiratory track illness and 2-12 months urine, throat and stool for immune compromised

patients.

Viral isolation in cell culture requires primary human embryonic kidneys, established

human epithelial cell lines. Since the above materials are unavailable or difficult to maintain

we need to adapt to novel techniques. Isolates can be identified by immunofluorescence tests

using an anti hexon antibody and infected cells. HI and Nt tests measure type specific

antigens and can be used to identify specific serotypes.

The disease can be rapidly detected using shell vial technique. The viral specimens

are centrifuged directly into tissue cell culture. Cells incubated for 1-2 days and then tested

with monoclonal antibodies directed against the group reactive epitope on the hexanantigen.

Polymerase chain reaction assays can be used for diagnosis of adenoviral infection in

tissue samples or body fluids. Using primers form conserved viral sequence we can detect all

sero types. This method uses single primer pair that attacks conserved segments that bracket a

hyper viable region in the gene. The assay can detect all known serotypes of human

Adenovirus. This method is rapid. Fastidious enteric adenovirus can be detected through

electron microscopy, ELISA or latex agglutination.


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Epidemiology:

Adenoviruses are present in all parts of the world. The most common serotypes in

clinical samples are low numbered respiratory type (1,2,3,5,7) of which 1, 2, 5, 6 occur in the

early stages of life 3 and 7 during school and 4,8 and 19 are not related with adult hood, and

gastrointestinal types( 40, 41). They are spread through direct contact, fecal-oral route,

respiratory droplets and contaminated fomites.

Prevention and control:

Careful hand washing is the best way to prevent infection. To prevent the spread

disinfection of the environmental surface with sodium hypochlorite is advisable. The risk of

water borne infection can be minimized by chlorinating it. Strict aseptic condition should be

observed to control the spread keratoconjunctivitis.

Treatment for respiratory infection may include: intake of fluids either intravenous or

through electrolyte because of dehydration due to fluid loss, Bronchodilator medications may

be used to open your child's airways. These medications are often administered in an aerosol

mist by a mask or through an inhaler. The adenovirus vaccines were used to control the

spread of the disease. The manufacture of vaccine was stopped in 1999 is no longer available.

Adenoviruses responsible for obesity:

The research on "Adipogenic potential of multiple human adenoviruses in vivo and in

vitro in animals," in the January issue of the American Journal of Physiology-Regulatory,

Integrative and Comparative Physiology published by the American Physiological Society.

The study, by Whigham et al, of the University of Wisconsin, found that the human

adenovirus Ad-37 causes obesity in chickens. This finding builds on studies that two related

viruses, Ad-36 and Ad-5, also cause obesity in animals. The finding of AD-36 in obese

humans gives a reason to study the cause of the viruses in obesity. The scientists inoculated

AD-37, AD-5 and a control in the chickens. They studied the serum lipid, visceral fat, total

body fat and viral antibodies and found that the AD-37 infected group weighed heavier than

that of other group. The authors concluded that the adenovirus may be responsible for obesity

in humans.

Conclusion:

Adenoviruses are group of DNA viruses which are responsible for some of the

common sickness. These viruses are now genetically engineered and are under laboratory

test. They can be used in the treatment of cancer causing genes, tumor cells etc. since they

can interact with the host DNA. 30% of the diseases such as obesity are attributed to them.

Path breaking researches are on to find out the percentage of the virus causing obesity.


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Name: Location: Known Functions:

II Hexon monomer Structural

III Penton base Penetration

IIIa Associated with penton base Penetration

IV Fibre Receptor binding; haemagglutination

V Core: associated with DNA & penton base Histone-like; packaging?

VI Hexon minor polypeptide Stabilization/assembly of particle?

VII Core Histone-like

VIII Hexon minor polypeptide Stabilization/assembly of particle?

IX Hexon minor polypeptide Stabilization/assembly of particle?

TP Genome - Terminal Protein Genome replication

Mu Nucleoprotein Genome replication?

IV2a Nucleoprotein Genome packaging

Protease Associated with pentons? Maturation


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