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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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BIBLIOGRAPHY
Andersson, Carina. Classification of Adenoviruses -Serological and Genetic Typing.
Projekt mikrobiell bioteknik TVMB04 Teknisk Biologi, vt 2006.
Catalysis of Adenovirus DNA Synthesis in vitro by DNA Polymerase. Journal of General
Virology (I98O), 48, 231-236
Jaturong Sewatanon Sirawat Srichatrapimuk Prasert Auewarakul. Compositional Bias and
Size of Genomes of Human DNA viruses. Inter Virology 2007;50:123132
Jawetz., Melnick., &Adelbergs. Medical Microbiology, 24th edition. Colombus: The
McGraw-Hill companies, Inc., 2007. 419-427.
Lober, Christian. Lenz-Sto ppler, Claudia. Dobbelstein, Matthias. Adenovirus
E1-transformed cells grow despite the continuouspresence of transcriptionally active
p53. Journal of General Virology (2002), 83, 20472057
Lodish et al. Molecular Cell Biology fifth edition. New York: W. H. Freeman, 2003.
Mark K. Kenny and Jerardh Urwitz. Initiation of Adenovirus DNA Replication, II.Structural
Requirements Using Synthetic Oligonucleotide Adenovirus Templates The Journal
of Biochemistry 1988. Vol. 263, No. 20, Issue Of July 15, Pp. 9809-9817
Prescott, Lancing M, Harley , Klein's. Microbiology 5th edition. Colombus: The
McGrawHill Companies, 2002.
Russell, W. C. Adenoviruses: update on structure and function Journal of General Virology
2009, 90, 120.
Russel, W.C. Update on adenovirus and its vectors. Journal of General Virology.2000, 81,
25732604.
Strauss, Ellen G. Viruses and Human Disease 2ndedition. California: Academic Press
Elsevier, 2007
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Vangipuram, Sharada D., Sheele, Jonathan., Atkinson, Richard L., Holland,Thomas C., and
Dhurandha, Nikhil V. A Human Adenovirus Enhances Preadipocyte
Differentiation. OBESITY RESEARCH Vol. 12 No. 5 May 2004
Torotora, Gerard J., Funke, Berdell R., Case, Christine L. Microbiology 9th edition.
Delhi: Pearson Education Inc., 2008,401-404.
1 Jan 2008. Les Laboratories Servier. 25 July 2009.
1 Jan 2009. Microbiology Bytes. 30 July 2009.
1 Jan 2005. Drek Wrong. 15 July 2009.
1 May 1995.D. Sander, 1995-2007. 8 Aug 2009.
American Physiological Society. "Contagious Obesity? Identifying The Human Adenoviruses
That May Make Us Fat." ScienceDaily 30 January 2006. 14 August 2009
.
28January 2008. Rector and Visitors of the University of Virginia.14 July 2009
14 Aug 2009. Semmelweis University 1 Jan 2006. Dna Viruses Adenoviruses Parvoviruses
Poxviruses. Adam, Eva.< http://mikrobiologia.sote.hu>
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