Viral Structure and Function
Adenoviruses are double-stranded DNA viruses. They have icosahedral
capsids with twelve vertices and seven surface proteins. The virion is
non-enveloped, spherical and about seventy to ninety nm in size. The
genome encodes about thirty proteins. Both strands of adenovirus DNA
encode genes. Transcription occurs in three stages -- immediate early,
early and late.
Adenovirus-Associated Human Disease
Pharyngitis
Acute Respiratory Disease
Pneumonia
Pharyngoconjunctival Fever
Epidemic Keratoconjuntivitis
Genitourinary Infections (cervicitis, urethritis, hemorrhagic cystitis)
Gasteroenteritis
Some asymptomatic and persistent infection
Adenovirus oncogenically tranforms rodent cells but not human cells.
Transmission
Ingestion/Fecal-Oral Route
Respiration (through respiratory droplets)
Contact/Hand-to-eye transfer
Venereal
Clinical Course and Diagnosis
Incubation Period: 5 to 8 days
Adenovirus usually causes a localized infection, but generalized infection
can occur in immuno-compromised patients.
Some adenovirus subtypes cause cellular cytopathic effect -- rounded,
swollen cells and basophilic intranuclear inclusions.
Adenovirus is responsible for five percent of acute respiratory childhood
illness and ten percent of infantile gasteroenteritis.
Meningoencephalatis is a complication of respiratory adenovirus infection.
Deaths may occur from adenovirus especially from infection by human
adenovirus type 7.
Diagnosis occurs through enzyme immunoassay, immunofluorescence
techniques and virus isolation in cell cultures.
Treatment and Therapy
Antivirals have generally been ineffective against
adenovirus infection. Intravenous ribavirin is a potential treatment.
Adenovirus infection results in long-lasting immunity against the specific
serotype. Maternal antibody is protective.
Prevention
Chlorination of swimming pools, drinking water, wastewater
High hygiene standards in opthamology practice
Hand-washing
Measures to prevent nosocomial transmission
Vaccination
The vaccine against adenovirus is live, oral and attenuated in the
intestine. Mucosal and intestinal immunity result. Vaccines are
administered to the military but not available for general use because of
concern about the live vaccine's oncogenic potential and the level of
attenuation achieved in children.
A Successful Vector for Vaccination and Gene Therapy
Adenoviruses have immense potential as vectors for vaccination and
for gene therapy because adenoviruses can be genetically altered in vitro
to:
(1) code for specific proteins
(2) not produce infectious, pathogenic viral offspring.
Vaccination:
A DNA segment that codes for an antigen that stimulates
an immune response in humans can be inserted into the genome of adenovirus
and then inserted into a host. Hepatitis B, HIV, herpes simplex, rabies
and respiratory synctial virus regions can be inserted into adenovirus DNA.
Gene Therapy:
A DNA segment that codes for an enzyme or protein product that corrects a
human genetic defect can be delivered to the host by an adenovirus
vector. For example, a normal copy of the defective gene in cystic
fibrosis patients can be inserted into patients through an adenovirus
vector.
Cystic Fibrosis Gene Therapy Trial Based on Adenovirus Vector
Professor Robert Siegel's Home Page
White and Fenner. Medical Virology, 4th edition. Academic Press: San Diego, 1994. pp.306-315.
Yang, Yiping, et. al. "Inactivation of E2a in Recombinant Adenoviruses Improves the Prospect for Gene Therapy in Cystic Fibrosis." Nature Genetics. Vol.7. July, 1994. pp. 362-369.
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Last modified: March 7, 1998