Adenoviruses are medium-sized (90-100 nm), nonenveloped icosahedral viruses containing double-stranded DNA. There are more than 49 immunologically distinct types (6 subgenera: A through F) that can cause human infections. Adenoviruses are unusually stable to chemical or physical agents and adverse pH conditions, allowing for prolonged survival outside of the body.
The adenovirus infection cycle can be clearly divided into two phases, which are separated by viral DNA replication. The first or “early” phase covers the entry of the virus into the host cell and the entry of the virus genome to the nucleus. The late genes are transcribed from the major late promoter. The “late” phase is involved in making gene products that are related to production and assembly of capsid proteins.
Adenoviral genes Function
Early genes (E): E1A, E1B, E2, E3, E4 Adenoviral gene transcription, replication, host immune suppression, inhibition of host cell apoptosis
Delayed early genes: IX, IVa2 Packaging
Major late Unit (L) Assembly
Virus packaged by transfecting HEK 293 cells with adenoviral-based vectors is capable of infecting human cells. These viral supernatants could, depending on the gene insert, contain potentially hazardous recombinant virus. Similar vectors have been approved for human gene therapy trials, attesting to their potential ability to express genes in vivo. For these reasons, due caution must be exercised in the production and handling of any recombinant adenovirus.
The probability of producing replication competent adenovirus (RCA), although low, increases with each successive amplification. RCA is produced when adenoviral DNA recombines with E1- containing genomic DNA in HEK 293 cells. It is suggested to use early amplification stocks when needed to produce additional quantities of adenovirus.
What are the hazards?
Adenoviruses most commonly cause respiratory illness; however, depending on the infecting serotype, they may also cause various other illnesses, such as gastroenteritis, conjunctivitis, cystitis, and rash-associated illnesses. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis. Patients with compromised immune systems are especially susceptible to severe complications of adenovirus infection that can cause more systemic diseases (e.g. hepatitis).
Although epidemiologic characteristics of the adenoviruses vary by type, all are transmitted by direct contact, fecal-oral transmission, and occasionally waterborne transmission. Some types are capable of establishing persistent asymptomatic infections in tonsils, adenoids, and intestines of infected hosts, and shedding can occur for months or years. Some adenoviruses (e.g., serotypes 1, 2, 5, and 6) have been shown to be endemic in parts of the world where they have been studied, and infection is usually acquired during childhood. Other types cause sporadic infection and occasional outbreaks; for example, epidemic keratoconjunctivitis is associated with adenovirus serotypes 8, 19, and 37. Epidemics of febrile disease with conjunctivitis are associated with waterborne transmission of some adenovirus types. ARD is most often associated with adenovirus types 4 and 7 in the United States. Enteric adenoviruses 40 and 41 cause gastroenteritis, usually in children. For some adenovirus serotypes, the clinical spectrum of disease associated with infection varies depending on the site of infection; for example, infection with adenovirus 7 acquired by inhalation is associated with severe lower respiratory tract disease, whereas oral transmission of the virus typically causes no or mild disease.
Ingestion; droplet exposure of the mucous membrane.
|Exposure of mucus membrane (eyes, nose, mouth)||Use of safety goggles or full face shields. Use of appropriate face mask|
|Injection||Use of safety needles; NEVER re-cap needle or remove needle from syringe|
|Aerosol inhalation||Use of appropriate respiratory protection|
|Direct contact with skin||Gloves, lab coat, closed shoes|
The above PPE are often required IN ADDITION to working in a certified Biosafety Cabinet.
Susceptibility to disinfectants: Susceptible to 1% sodium hypochlorite, 2% glutaraldehyde, 0.25% sodium dodecyl sulfate
Use in Lab: BSL-2
Use with Animals: ABSL-2 housing post injection/exposure of animals. In rodents in the absence of human cells, ABSL-2 for 48h then ABSL-1.
Most infections are mild and require no therapy or only symptomatic treatment. Because there is no virus-specific therapy, serious adenovirus illness can be managed only by treating symptoms and complications of the infection.