Adenoviridae
Adenoviruses | |
---|---|
Transmission electron micrograph of two adenovirus particles | |
Virus classification | |
(unranked): | Virus |
Realm: | Varidnaviria |
Kingdom: | Bamfordvirae |
Phylum: | Preplasmiviricota |
Class: | Tectiliviricetes |
Order: | Rowavirales |
Family: | Adenoviridae |
Genera | |
|
Adenoviruses (members of the
They have a broad range of vertebrate hosts; in humans, more than 50 distinct adenoviral serotypes have been found to cause a wide range of illnesses, from mild respiratory infections in young children (known as the common cold) to life-threatening multi-organ disease in people with a weakened immune system.[2]
Virology
Classification
This family contains the following genera:[4]
- Atadenovirus
- Aviadenovirus
- Ichtadenovirus
- Mastadenovirus (including all human adenoviruses)
- Siadenovirus
- Testadenovirus
Diversity
In humans, currently there are 88 human adenoviruses (HAdVs) in seven species (Human adenovirus A to G):[5]
- A: 12, 18, 31
- B: 3, 7, 11, 14, 16, 21, 34, 35, 50, 55
- C: 1, 2, 5, 6, 57[6]
- D: 8, 9, 10, 13, 15, 17, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 33, 36, 37, 38, 39, 42, 43, 44, 45, 46, 47, 48, 49, 51, 53, 54, 56,[7] 58, 59, 60, 62, 63,[8] 64, 65, 67, 69,[9] 70, 71, 72, 73, 74, 75
- E: 4
- F: 40, 41[10]
- G: 52[11]
Different types/serotypes are associated with different conditions:[12]
- respiratory disease (mainly species HAdV-B and C)
- conjunctivitis (HAdV-B and D)
- gastroenteritis (HAdV-F types 40, 41, HAdV-G type 52)
- obesity or adipogenesis (HAdV-A type 31, HAdV-C type 5, HAdV-D types 9, 36, 37) [13]
All these types are called Human mastadenovirus A–G by the ICTV, because all are members of the genus Mastadenovirus.
Structure
Adenoviruses are medium-sized (90–100 nm).
In 2010, the structure of the human adenovirus was solved at the atomic level, making it the largest high-resolution model ever. The virus is composed of around 1 million
Genome
The adenovirus genome is linear, non-segmented double-stranded (ds) DNA that is between 26 and 48
Replication
Adenoviruses possess a linear dsDNA
Once the virus has successfully gained entry into the host cell, the endosome acidifies, which alters virus topology by causing capsid components to disband. The capsid is destabilized and protein VI, which is one of the capsid constituents (see
The adenovirus
The early genes are responsible for expressing mainly non-structural, regulatory
Some adenoviruses under specialized conditions can transform cells using their early gene products.
DNA replication separates the early and late phases. Once the early genes have liberated adequate virus proteins, replication machinery, and replication substrates, replication of the adenovirus genome can occur. A terminal protein that is covalently bound to the 5' end of the adenovirus genome acts as a primer for replication. The viral DNA polymerase then uses a strand displacement mechanism, as opposed to the conventional Okazaki fragments used in mammalian DNA replication, to replicate the genome.
The late phase of the adenovirus lifecycle is focused on producing sufficient quantities of structural protein to pack all the genetic material produced by DNA replication.[2] Once the viral components have successfully been replicated, the virus is assembled into its protein shells and released from the cell as a result of virally induced cell lysis.[2]
Multiplicity reactivation
Adenovirus is capable of multiplicity reactivation (MR)[25] (Yamamoto and Shimojo, 1971). MR is the process by which two, or more, virus genomes containing lethal damage interact within the infected cell to form a viable virus genome. Such MR was demonstrated for adenovirus 12 after virions were irradiated with UV light and allowed to undergo multiple infection of host cells.[25] In a review, numerous examples of MR in different viruses were described, and it was suggested that MR is a common form of sexual interaction that provides the survival advantage of recombinational repair of genome damages.[26]
Epidemiology
Transmission
Adenoviruses are unusually stable to
Humans
Humans infected with adenoviruses display a wide range of responses, from no symptoms at all to the severe infections typical of Adenovirus serotype 14.
Animals
Two types of canine adenoviruses are well known, type 1 and 2. Type 1 (CAdV-1) causes infectious canine hepatitis, a potentially fatal disease involving vasculitis and hepatitis. Type 1 infection can also cause respiratory and eye infections. CAdV-1 also affects foxes (Vulpes vulpes and Vulpes lagopus) and may cause hepatitis and encephalitis. Canine adenovirus 2 (CAdV-2) is one of the potential causes of kennel cough. Core vaccines for dogs include attenuated live CAdV-2, which produces immunity to CAdV-1 and CAdV-2. CAdV-1 was initially used in a vaccine for dogs, but corneal edema was a common complication.[31]
Squirrel adenovirus (SqAdV) is reported to cause enteritis in red squirrels in Europe, while gray squirrels seem to be resistant. SqAdV is most closely related to the adenovirus of guinea pigs (GpAdV).
Adenoviruses are also known to cause respiratory infections in horses, cattle, pigs, sheep, and goats. Equine adenovirus 1 can also cause fatal disease in immunocompromised Arabian foals, involving pneumonia and destruction of pancreatic and salivary gland tissue.[31] Tupaia adenovirus (TAV) (tree shrew adenovirus 1) has been isolated from tree shrews.
Otarine adenovirus 1 has been isolated from sea lions (Zalophus californianus).[32]
The fowl adenoviruses are associated with many disease conditions in domestic fowl like inclusion body hepatitis, hydropericardium syndrome,[33] Egg drop syndrome, Quail bronchitis, Gizzard erosions and many respiratory conditions. They have also been isolated from wild black kites (Milvus migrans).[34]
Titi monkey adenovirus was isolated from a colony of monkeys.[35]
Prevention
Currently there is a vaccine for adenovirus type 4 and 7 for US military personnel only. US military personnel are the recipients of this vaccine because they may be at a higher risk of infection.[citation needed] The vaccine contains a live virus, which may be shed in stool and lead to transmission. The vaccine is not approved for use outside of the military, as it has not been tested in studied in the general population or on people with weakened immune systems.[36]
In the past, US military recruits were vaccinated against two serotypes of adenovirus, with a corresponding decrease in illnesses caused by those serotypes. That vaccine is no longer manufactured. The U.S. Army Medical Research and Materiel Command announced on 31 October 2011 that a new adenovirus vaccine, which replaces the older version that has been out of production for over a decade, was shipped to basic training sites on 18 October 2011. More information is available here.[37]
Prevention of adenovirus, as well as other respiratory illnesses, involves frequent hand washing for more than 20 seconds, avoiding touching the eyes, face, and nose with unwashed hands, and avoiding close contact with people with symptomatic adenovirus infection. Those with symptomatic adenovirus infection are additionally advised to cough or sneeze into the arm or elbow instead of the hand, to avoid sharing cups and eating utensils, and to refrain from kissing others. Chlorination of swimming pools can prevent outbreaks of conjunctivitis caused by adenovirus.[36]
Diagnosis
Diagnosis is from symptoms and history. Tests are only necessary in very serious cases. Tests include blood tests, eyes, nose or throat swabs, stool sample tests, and chest x-rays.[38] In the laboratory, adenovirus can be identified with antigen detection, polymerase chain reaction (PCR), virus isolation and serology. Even if adenovirus is found to be present, it may not be the cause of any symptoms. Some immunocompromised individuals can shed the virus for weeks and show no symptoms.[39]
Infections
Most infections with adenovirus result in infections of the upper respiratory tract. Adenovirus infections often present as
Some children (especially the youngest) can develop adenovirus bronchiolitis or pneumonia, both of which can be severe. In babies, adenoviruses can also cause coughing fits that look almost exactly like whooping cough. Adenoviruses can also cause viral meningitis or encephalitis. Rarely, adenovirus can cause hemorrhagic cystitis (inflammation of the urinary bladder—a form of urinary tract infection—with blood in the urine).
Most people recover from adenovirus infections by themselves, but people with immunodeficiency sometimes die of adenovirus infections, and—rarely—even previously healthy people can die of these infections.[42] This may be because sometimes adenoviral infection can lead to cardiac disorders. For example, in one study, some cardiac samples of patients with dilated cardiomyopathy were positive for presence of adenovirus type 8.[43]
Adenoviruses are often transmitted by expectoration (e.g. aerosols), but they can also be transmitted by contact with an infected person, or by virus particles left on objects such as towels and faucet handles. Some people with adenovirus gastroenteritis may shed the virus in their stools for months after getting over the symptoms. The virus can be passed through water in swimming pools that are not sufficiently chlorinated.
As with many other illnesses, good handwashing practice is one way to inhibit the person-to-person transmission of adenoviruses. Heat and bleach will kill adenoviruses on objects.[citation needed]
Treatment
There are no proven antiviral drugs to treat adenoviral infections, so treatment is largely directed at the symptoms (such as
Use in gene therapy and vaccination
Gene therapy
Adenoviruses have long been a popular
A safety issue with adenoviruses is that they can cause an immune response with a related inflammatory response as occurred in the death
Adenovirus has been used for delivery of CRISPR/Cas9 gene editing systems, but high immune reactivity to viral infection has posed challenges in use for patients.
Vaccines
Modified (recombinant) adenovirus vectors, including replication incompetent types, can deliver DNA coding for specific antigens.[50]
Adenovirus have been used to produce
Possible issues with using Adenovirus as vaccine vectors include: the human body develops immunity to the vector itself, making subsequent booster shots difficult or impossible.[58] In some cases, people have pre-existing immunity to Adenoviruses, making vector delivery ineffective.[59]
HIV infection concerns
This section needs more primary sources. (April 2021) |
The use of Ad5 vaccines for COVID-19 worried researchers who had experience with two failed trials of an Ad5 vaccine, Phambili and STEP, due to the increased risk for uncircumcised male patients of contracting
By comparison, a
See also
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