Adenovirus

In 1953, Rowe and his colleagues observed degeneration of adenoid tissue removed after surgery and retained for culture. A virus was later identified to be responsible for these degenerative changes. It was named adenovirus to signify the area from which it was isolated.

This virus was capable of causing latent infections, not only of the adenoid tissue, but also of the respiratory tract.

Current interest in Adenoviruses

Apart from causing acute clinical illness of the respiratory tract and the conjunctiva, renewed interest in this virus is related to its ability to produce tumors in animals. Other important biological characteristics of the virus that have attracted the attention of scientists are as follows:

  • Ability to transform tissue culture cells into malignant cells
  • Ability to cause latent infection in a variety of tissues belonging to different hosts
  • Induction or inhibition of apoptosis by expression or suppression of early viral proteins
  • Its capacity to act as a vector for the carriage of genetic material from other viruses. This property has been crucial in the development of live virus vaccines.
  • Attempts have also been made to utilize Adenoviruses as vectors for gene therapy for the regeneration of the central nervous system, treatment of inherited cardiomyopathies, hematopoetic malignancies, cystic fibrosis and colon cancers

Structure of Adenovirus

It is a non-enveloped double stranded DNA virus with an icosahedral symmetry. The family of adenoviruses has been classified into adenoviruses causing diseases in mammals (mastadenoviruses) and those causing disease in birds (aviadenovirus). The mastadenoviruses causing infections in humans has been further classified based on antigenecity into six subgenera (A through F). At least 51 different serotypes of human mastadenoviruses are known.  They are designated by the letter h for human and a type number e. g mastadenovirus h 3. 

Pathogenesis

Adenoviruses are capable of three types of interaction with host cells.

  • Lytic cycle: This occurs in human cells resulting in cell death and release of approximately 1 million progeny virions with only 1 % to 5% of them being infective.
  • Latent infection: Also known as chronic infection, latency is seen in the lymphoid tissues. A small number of viruses are released into the circulation during latency.
  • Oncogenic transformation: In this type of virus to host cell interaction, only the initial steps of viral replication take place and then the viral genome integrates with the host cell genome to bring about an oncogenic transformation. No infectious virions are produced in this type of interaction. 

Clinical syndromes

Adenoviruses affect humans across the lifespan. It has been observed that specific serotypes are causative agents in specific clinical syndromes in humans. In neonates, a disseminated infection is seen with serotypes 3, 7, 21 and 30. In infants, coryza and pharyngitis are caused by serotypes 1, 2 and 5. In children, adenovirus infections are common and cause upper respiratory disease (1,2,4-6), diarrhea (2,3,5,40,41), intussception (1,2,4,5), meningoencephalitis (2,6,7,12) and hemorrhagic cystitis (7,11,21). Adenoviruses causes acute respiratory disease and pneumonia in young adults (3,4,7). Serotypes 8, 19 and 37 have been implicated in epidemic keratoconjunctivitis in adults. In the immunocompromised group, adenoviruses are known to cause the following:

  • intestinal infections 
  • pneumonia with dissemination 
  • urinary tract infection
  • meningoencephalitis. 

Respiratory infections

Majority of the respiratory infections caused by adenovirus are asymptomatic. Adenovirus type 7 is known to cause a fulminant bronchiolitis and pneumonia. Cough, fever, sore throat and runny nose are common presenting symptoms of adenovirus infections. Physical findings are often correlated with the symptoms of the patient. Serotypes 4 & 7 are associated with features of atypical pneumonia where the physical findings may not match the findings of the roentgenogram. 

Pharyngoconjunctival fever

This is a characteristic syndrome in children which is attributed to adenoviruses. It is characterized by fever (38 ° C), pharyngitis, rhinitis, conjunctivitis and cervical adenitis. The symptoms persist for 3 to 5 days. Complications are rare and several studies have identified serotype 3 to be the most commonly involved organism. Contaminated swimming pools and ponds are known to be the source of infection.   

Epidemic keratoconjunctivitis

Jawetz et al pointed out the role of adenoviruses in epidemic keratoconjunctivitis in 1955. The incubation period is 4 to 24 days and conjunctivitis persists for 1 to 4 weeks. Involvement of the cornea produces visual disturbances. Type 8 is commonly involved in epidemics, however major epidemics have also been caused by types 19 and 37. 

Hemorrhagic cystitis

Adenovirus types 11 and 21 are frequently isolated from cases of hemorrhagic cystitis. Viral hemorrhagic cystitis shows a greater preponderance towards males than females. The average duration of gross hematuria is about 3 days. 

Diarrhea

Adenoviruses have been seen in patients having diarrhea, especially children. Types 40 and 41 have been associated with diarrhea. They have also been isolated from mesenteric adenitis and intussusception in children.
Laboratory diagnosis:

  • The diagnosis can be established by isolation of the virus from different human specimens such as feces, respiratory secretions or urine.
  • Polymerase chain reactions can also be used on suspected specimens.
  • Complement fixation tests and neutralizing antibody tests can be performed for serotyping.
  • Immunofluoresecence with targeted antibodies is another important diagnostic tool. 
  • Electron microscopy is a useful tool from the research point of view. 

Treatment and prevention

Most adenoviral infections are self-limiting and the incidence of complications and mortality are very rare. Therefore, treatment is only symptomatic. Killed and live vaccines have been developed against serotypes 4 and 7 to be administered to military recruits for the prevention of Adult Respiratory Disease (ARD). Vaccines are not available for general use due to the large number of serotypes capable of causing infection. Prevention and control are important in cases of outbreaks. Improving hygiene and hand washing practices are crucial in limiting the spread during outbreaks. Swimming pool associated outbreaks can be prevented by adequate chlorination. 

Adeno-Associated viruses (AAV)

They are small viral particles 20nm to 25nm in diameter. AAV are incapable of independent replication as they do not possess enough DNA. They multiply only in cells which are simultaneously infected by adenovirus. Hence they are also called Adeno- satellite viruses. Four serotypes have been identified of which type 1, 2 and 3 are of human origin while type 4 is of simian origin. Though their pathogenic role in humans is uncertain, AAV has gained heightened interest recently due to their potential to become vectors for carriage of genetic material e.g. AAV being used as a vector for the development of  HIV vaccine.