Adenovirus Case File

Adenovirus Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 24

A 5-year-old girl is brought to the physician’s office because of “pink eye.” She was sent home from kindergarten yesterday by the school nurse because her left eye was red. When she awakened this morning, the right eye was red as well. She has had watery drainage but no purulent discharge. She’s had a mild head cold with a runny nose and a mild sore throat but no fever. When her mother called the school this morning, she was told that five of her daughter’s classmates were out with pink eye today. On examination, the child has injected conjunctiva bilaterally with clear drainage. No crusting of the lashes is noted, and the corneas are clear. She has mildly tender preauricular adenopathy. The remainder of her examination is unremarkable.

◆ What organism is the most likely cause of this infection?

◆ How does this organism gain entry into host cells?

ANSWERS TO CASE 24: ADENOVIRUS

Summary: A 5-year-old girl with conjunctivitis of both eyes, with nonpurulent drainage associated with an upper respiratory infection.

◆ Most likely organism causing the infection: Adenovirus.

◆ Method that the organism gains entry into host cells: Adenoviruses gain entry into host cells by binding to the coxsackie adenovirus receptor (CAR) followed by receptor-mediated endocytosis.

CLINICAL CORRELATION

Conjunctivitis is a normal feature of many childhood infections. However, the most common cause of conjunctivitis is related to infection with adenoviruses. In addition to being the most common cause of viral conjunctivitis, adenoviruses also commonly cause upper respiratory infections and gastrointestinal infections. Most adenoviral diseases are mild and self-limiting in immunecompetent persons. Children are infected more frequently than adults.

APPROACH TO SUSPECTED ADENOVIRAL INFECTION

Objectives

1. Be able to describe the characteristics of adenovirus.
2. Understand how adenovirus causes infection.
3. Know the strategies of prevention.

Definitions

Conjunctivitis: Inflammation of the eye tissue.

Lymphadenopathy: Enlargement of a lymph node occurring singly or in multiple nodes.

Preauricular adenopathy: Enlargement of a lymph node occurring singly or in multiple nodes anterior to the ear.

DISCUSSION

Characteristics of Adenoviruses That Impact Transmission

Adenoviruses are nonenveloped viruses that contain linear, doublestranded DNA with a terminal protein attached to both 5′ ends of the genome. The viral capsid is composed of an icosadeltahedral structure that contains a penton base and fiber at each vertex. The fibers contain viral attachment proteins that determine the target cell specificity among viral serotypes. The fiber also serves as a hemagglutinin. Over 100 different serotypes have been recognized, more than 49 of which are known to infect humans.

To gain entry into the host cell, the viral fiber proteins bind to the coxsackie adenovirus receptor on host cell surfaces and become internalized by receptor-mediated endocytosis. The virus then lyses the endosome, and the viral DNA is delivered to the host nucleus still within the viral capsid. Viral DNA replication occurs in the nucleus, via a virally encoded DNA polymerase, and the viral capsid proteins are made in the cytoplasm and then transported to the nucleus for viral assembly. Adenoviral genes are transcribed from both strands of the DNA genome in either direction at different times during viral replication. A single viral replication cycle takes approximately 32–36 hours and produces around 10,000 new virions. Figure 24-1 shows the replication cycle. However, errors in assembly and replication are common, resulting in a much lower number of infectious viral particles.

Adenoviruses infect epithelial cells of the respiratory tract, conjunctiva, and enteric organs. Infections are spread from person to person by aerosolized respiratory droplets, close contact, or a fecal-oral route. Fomite transmission is also common because adenoviruses are nonenveloped, making them more resistant to detergents and desiccation. They can cause lytic infections in epithelial cells and tend to cause latent infections in lymphoid tissue. Persistence in lymphoid tissues involves integration of viral DNA into the host genome. Reactivation of virus can occur with stress. Viremia may occur and cause spread to distant organs such as the kidney, bladder, liver, and lymphoid tissue. Viremia is especially common in immunosuppressed patients.

Diagnosis

Adenoviruses primarily infect children under 3 years and appear clinically with a variety of symptoms including fever, cough, nonstreptococcal exudative pharyngitis, cervical adenitis, conjunctivitis, or gastroenteritis. Symptoms can last from 3 to 5 days. More severe respiratory diseases include laryngitis, bronchiolitis, and pneumonia. Reactivated viral disease occurs primarily in immune compromised individuals. Adenoviral follicular conjunctivitis, or “pink eye,” outbreaks in children often involve swimming pools as a common source of infection. Gastroenteritis is also a major clinical manifestation of adenoviral infection. Adenoviral types 40, 41, and 42 have been shown to be associated with gastrointestinal disease in infants and hospitalized patients.

In addition to clinical presentation of infection, laboratory diagnostic tests, including cell culture, ELISA (enzyme-linked immunosorbent assay), PCR, and DNA-probe analysis are available and can be used to detect the viral type in clinical samples and tissue culture. However, their primary use is for epidemiological studies, and they are not used widely in clinical practice for diagnostic purposes. Typically, diagnosis is made by clinical presentation and patient history.

Figure 24-1. Adenovirus replication cycle.

Treatment and Prevention

Currently, there is no treatment for adenoviral infection. Live oral vaccines have been developed for adenovirus types 4 and 7, which cause acute respiratory tract infections, and have been used primarily in military settings. However, because some adenoviruses are oncogenic, such vaccines have not been made available to the general population. Thus, prevention is the most important aspect involving careful hygiene, handwashing, and isolation of infected individuals.

COMPREHENSION QUESTIONS

[24.1] An 11-year-old boy attending summer Boy Scout camp develops symptoms of sore throat, headache, fatigue, and conjunctivitis. He is seen by the camp medical staff and on examination is found to have a slight fever of 39.8°C (103.6°F), but no rash. Within the next 1–2 days, several of the other campers develop similar symptoms, which last for 5–7 days. The larger number of campers with similar symptoms indicates that a common source of infection is causing the outbreak. Which of the following activities is the most likely source of the campers’ infection?

A. Hiking in wooded areas with tall grass

B. Sharing water canteens with other campers

C. Sleeping outdoors without protective netting

D. Swimming in the camp pond

E. Walking barefoot in the bath house

[24.2] The causative agent in the question above was determined to be an adenoviral infection. Which of the following best describes this viral agent?

A. Nonenveloped, double-stranded DNA virus with fibers at its vertices

B. Nonenveloped, double-stranded, circular DNA virus

C. Enveloped, single-stranded, negative-sense RNA virus

D. Enveloped, double-stranded, linear DNA virus with glycoprotein spikes

E. Enveloped, double-stranded, circular DNA virus

[24.3] A 2-year-old child attending day care develops diarrhea and gastroenteritis as a result of an adenoviral infection. Which of the following adenoviral serotypes would most likely be responsible for this girl’s illness?

A. Type 4

B. Type 7

C. Type 19

D. Type 37

E. Type 41

Answers

[24.1] D. The campers’ symptoms are consistent with adenoviral conjunctivitis, which is commonly spread through contaminated swimming pools or ponds; answers A, B, C, and E are incorrect.

[24.2] A. Adenoviruses are nonenveloped, double-stranded linear DNA viruses with fiber structures projecting from their vertices or penton bases; answers B, C, D, and E are incorrect: (B) describes polyoma viruses such as human papillomavirus; (C) describes viruses such as rhabdoviruses, orthomyxoviruses, paramyxoviruses, and the like; (D) describes herpesviruses; (E) describes hepatitis B virus.

[24.3] E. Adenoviral types 40, 41, and 42 have been shown to be associated with gastrointestinal disease in infants; answers A, B, C, and D are incorrect: Adenoviral types 4 and 7, commonly cause upper respiratory infections in military recruits; adenoviral types 19 and 37 have been implicated in causing epidemic keratoconjunctivitis.

MICROBIOLOGY PEARLS ❖ Adenoviruses commonly cause conjunctivitis, in combination with pharyngitis, and upper respiratory infections. ❖ Children under 3 years and immunocompromised adults are at particular risk. ❖ Clinical manifestations are fever, cough, nonstreptococcal exudative pharyngitis, cervical adenitis, conjunctivitis, or gastroenteritis. ❖ No treatment or vaccination is available for the general public.

REFERENCES

Brooks GF, Butel JS, Morse SA. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 23rd ed. New York: McGraw-Hill, 2004:420–8. 

Ryan JR, Ray CG. Sherris Medical Microbiology, 4th ed. New York: McGraw-Hill, 2004:507–10. 

Shenk TE. Adenoviridae: the viruses and their replication. Fields Virology, 4th ed. Philadelphia, PA:Lippincott Williams & Wilkins, 2001:2111–35.

HomeMicrobiology Case FileAdenovirus Case File