Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Adenoviruses

  • Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Burke A Cunha, MD  more...
 
Updated: Mar 04, 2016
 

Background

Adenovirus, a DNA virus, was first isolated in the 1950s in adenoid tissue–derived cell cultures, hence the name. These primary cell cultures were often noted to spontaneously degenerate over time, and adenoviruses are now known to be a common cause of asymptomatic respiratory tract infection that produces in vitro cytolysis in these tissues.

A virus image from the International Committee on A virus image from the International Committee on Taxonomy of Viruses, in The Big Picture Book of Viruses, available at http://www.virology.net/Big_Virology/BVDNAadeno.html.

An extremely hardy virus, adenovirus is ubiquitous in human and animal populations, survives long periods outside a host, and is endemic throughout the year. Possessing 52 serotypes, adenovirus is recognized as the etiologic agent of various diverse syndromes. It is transmitted via direct inoculation to the conjunctiva, a fecal-oral route, aerosolized droplets, or exposure to infected tissue or blood.

The virus is capable of infecting multiple organ systems; however, most infections are asymptomatic. Adenovirus is often cultured from the pharynx and stool of asymptomatic children, and most adults have measurable titers of anti-adenovirus antibodies, implying prior infection. Adenovirus is known to be oncogenic in rodents but not in humans.

Adenovirus has been associated with both sporadic and epidemic disease and, with regard to infections among military recruits, who were routinely immunized against types 4 and 7 from 1971 until the cessation of vaccine production in 1996. Adenovirus became a significant cause of economic cost and morbidity in this setting. A live oral vaccine against adenovirus types 4 and 7 was approved for use in this population by the US Food and Drug Administration (FDA) in 2011, and subsequent incidence of acute respiratory disease declined.

Of interest is the role of adenoviruses as vectors in vaccination and in gene therapy.[1, 2, 3] Adenoviruses can infect various cells, both proliferating and quiescent, and thus hold the promise of targeting many different tissues and diseased cell lines.

The genome of adenovirus is well known and can be modified with relative ease to induce lysis or cytotoxicity of a specified cell line without affecting others.

The virus itself can be engineered to remove its replicative capacity by removing essential genes. Additionally, specific genes can be inserted into the virus that then can repair defective metabolic, enzymatic, or synthetic pathways in the host. Suicide gene systems that convert nontoxic systemically delivered prodrugs to active chemotherapeutic agents have been delivered via adenoviral vectors directly into cancer cells. However, the greatest challenge in viral gene therapy, as might be expected, is the immune response to the viral vector itself.

The complex mechanisms by which viral vectors may be incorporated into gene therapy and the rapid growth in this field put further discussion beyond the scope of this text.

Next

Pathophysiology

Adenovirus is a double-stranded DNA virus that measures 70-90 nm and that has an icosahedral capsid.

The site of entry generally determines the site of infection; respiratory tract infection infections result from droplet inhalation, while gastrointestinal tract involvement results from fecal-oral transmission. Upon infection with adenovirus, one of three different interactions with the cells may occur.

The first is lytic infection, which occurs when an adenovirus enters human epithelial cells and continues through an entire replication cycle, which results in cytolysis, cytokine production, and induction of host inflammatory response.

The second is chronic or latent infection, the exact mechanism of which is unknown, which frequently involves asymptomatic infection of lymphoid tissue.

Lastly, oncogenic transformation has been observed in rats. During oncogenesis, the replication cycle is truncated, and adenoviral DNA is then integrated into the host cell’s DNA. Thereafter, adenovirus produces potent E1A proteins that immortalize primary rodent cells by altering cellular transcription, ultimately leading to deregulation of apoptosis and malignant transformation.

Previous
Next

Epidemiology

Frequency

United States

Adenovirus is isolated most commonly in infants and children. An increased incidence of infection was found in military recruits until the introduction of an effective vaccine against serotype 4 (Ad4) and serotype 7 (Ad7) in 1971. The economy-driven cessation of vaccine production by its sole producer in 1996 resulted in re-emergence of outbreaks, with Ad4 predominating in 98% of cases. The reservoirs exist within the crowded training environment itself, and Ad4 has been detected on lockers, rifles, and bedding. Ad4 seropositivity of new recruits has been demonstrated to rise from 30% to almost 100%. Prolonged pharyngeal shedding and communal quarters contribute to outbreaks, with illness most commonly arising in weeks 3 to 5.

Lost productivity and interrupted military training prompted reinvestigation of vaccine production. Live oral adenovirus types 4 and 7 vaccine was approved by the FDA in 2011, significantly decreasing and the incidence of febrile respiratory illness. Notably, co-infection with non-vaccine strains (B1 and E) have developed following vaccination,[4] and surveillance for emerging non-vaccine strains is still needed.

In 2007, media attention following adenovirus outbreaks in the United States focused on serotype 14. The CDC's Morbidity and Mortality Weekly Review published an article entitled " Acute Respiratory Disease Associated with Adenovirus Serotype 14—Four States, 2006-2007."

Mortality/Morbidity

Severe morbidity and mortality associated with adenovirus infections are rare in immunocompetent hosts. Uncommon complications that increase the risk of mortality include meningoencephalitis and pneumonitis.

Severe adenovirus infections have been reported in immunocompromised patients, such as transplant patients and those with inherited and acquired immunodeficiency states. Mortality rates associated with adenovirus infections among pediatric and adult transplant recipients have varied from 6%-70%.[5]

Morbidity and deaths due to pronounced host inflammatory responses have occurred in past gene vector trials.

As with polio vaccines, live adenovirus vaccines in the 1950s became contaminated with simian virus 40 (SV40), with resulting concern that this virus caused various cancers. After subsequent long-term follow-up, some studies have found a moderate association between SV40 and human cancers as a transforming virus, while some other studies have reported no such findings.[6, 7]

Race

No racial predilection has been described.

Sex

Adenovirus urinary tract infections are more common in males. The prevalence of other syndromes does not appear to be affected by the sex of the individual.

Age

Adenovirus infection typically affects children from infancy to school age, but children of any age may be affected, including neonates. Young adults in any setting of close quarters and stress may be affected, as in the case of military trainees.

Previous
Next

Prognosis

The prognosis of adenovirus infection is generally good in immunocompetent hosts, but mortality rates may be as high as 70% in immunocompromised individuals.

Previous
 
 
Contributor Information and Disclosures
Author

Sandra G Gompf, MD, FACP, FIDSA Associate Professor of Infectious Diseases and International Medicine, University of South Florida College of Medicine; Chief, Infectious Diseases Section, Director, Occupational Health and Infection Control Programs, James A Haley Veterans Hospital

Sandra G Gompf, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Richard Oehler, MD Associate Professor, Department of Internal Medicine, Division of Infectious Diseases and International Medicine, University of South Florida College of Medicine; Director of Clinical Education, Division of Infectious Diseases, Tampa Veterans Affairs Medical Center

Richard Oehler, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Dhanashree Kelkar, MD Lecturer, Department of Medicine, Dr Vasantrao Pawar Medical College, Maharashtra University of Health Sciences, India

Dhanashree Kelkar, MD is a member of the following medical societies: American Medical Association, American Association of Physicians of Indian Origin

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

David Hall Shepp, MD Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine

David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Received salary from Gilead Sciences for management position.

References
  1. Kopecky-Bromberg SA, Palese P. Recombinant vectors as influenza vaccines. Curr Top Microbiol Immunol. 2009. 333:243-67. [Medline].

  2. Harvey AR, Hellström M, Rodger J. Gene therapy and transplantation in the retinofugal pathway. Prog Brain Res. 2009. 175:151-61. [Medline].

  3. Limbach KJ, Richie TL. Viral vectors in malaria vaccine development. Parasite Immunol. 2009 Sep. 31(9):501-19. [Medline].

  4. Vora GJ, Lin B, Gratwick K et al. Co-infections of adenovirus species in previously vaccinated patients. Emerg Infect Dis. June 2006. 12:921-30. [Medline].

  5. Echavarría M. Adenoviruses in immunocompromised hosts. Clin Microbiol Rev. 2008 Oct. 21(4):704-15. [Medline]. [Full Text].

  6. Shah KV. SV40 and human cancer: a review of recent data. Int J Cancer. 2007 Jan 15. 120(2):215-23. [Medline].

  7. Martini F, Corallini A, Balatti V, Sabbioni S, Pancaldi C, Tognon M. Simian virus 40 in humans. Infect Agent Cancer. 2007. 2:13. [Medline].

  8. Tabain I, Ljubin-Sternak S, Cepin-Bogovic J, Markovinovic L, Knezovic I, Mlinaric-Galinovic G. Adenovirus Respiratory Infections in Hospitalized Children: Clinical Findings in Relation to Species and Serotypes. Pediatr Infect Dis J. 2012 Apr 18. [Medline].

  9. Faden H, Wynn RJ, Campagna L, Ryan RM. Outbreak of adenovirus type 30 in a neonatal intensive care unit. J Pediatr. 2005 Apr. 146(4):523-7. [Medline].

  10. Kajon AE, Moseley JM, Metzgar D, Huong HS, Wadleigh A, Ryan MA. Molecular epidemiology of adenovirus type 4 infections in US military recruits in the postvaccination era (1997-2003). J Infect Dis. 2007 Jul 1. 196(1):67-75. [Medline].

  11. Russell KL, Hawksworth AW, Ryan MA et al. Vaccine-preventable adenoviral respiratory illness in US military recruits,1999-2004. Vaccine. April 2006. 15:2835-42. [Medline].

  12. Wirsing von König CH, Rott H, Bogaerts H, Schmitt HJ. A serologic study of organisms possibly associated with pertussis-like coughing. Pediatr Infect Dis J. 1998 Jul. 17(7):645-9. [Medline].

  13. Versteegh FG, Mooi-Kokenberg EA, Schellekens JF, Roord JJ. Bordetella pertussis and mixed infections. Minerva Pediatr. 2006 Apr. 58(2):131-7. [Medline].

  14. Dart JK, El-Amir AN, Maddison T, Desai P, Verma S, Hughes A, et al. Identification and control of nosocomial adenovirus keratoconjunctivitis in an ophthalmic department. Br J Ophthalmol. 2009 Jan. 93(1):18-20. [Medline].

  15. Bruno B, Zager RA, Boeckh MJ, et al. Adenovirus nephritis in hematopoietic stem-cell transplantation. Transplantation. 2004 Apr 15. 77(7):1049-57. [Medline].

  16. Nakamura Y, Ohashi K, Nakano N, Nemoto T, Funada N, Ando M. [Acute necrotizing tubulointerstitial nephritis due to adenoviral infection following hematopoietic stem cell transplantation: clinical findings obtained from 4 autopsy cases]. Nippon Jinzo Gakkai Shi. 2008. 50(8):1036-43. [Medline].

  17. Jalal H, Bibby DF, Tang JW, Bennett J, Kyriakou C, Peggs K. First reported outbreak of diarrhea due to adenovirus infection in a hematology unit for adults. J Clin Microbiol. 2005 Jun. 43(6):2575-80. [Medline].

  18. Ison MG. Adenovirus infections in transplant recipients. Clin Infect Dis. 2006 Aug 1. 43(3):331-9. [Medline].

  19. Hedderwick SA, Greenson JK, McGaughy VR, Clark NM. Adenovirus cholecystitis in a patient with AIDS. Clin Infect Dis. 1998 Apr. 26(4):997-9. [Medline].

  20. Liu M, Worley S, Arrigain S, Aurora P, Ballmann M, Boyer D, et al. Respiratory viral infections within one year after pediatric lung transplant. Transpl Infect Dis. 2009 Aug. 11(4):304-12. [Medline].

  21. Echavarria M, Sanchez JL, Kolavic-Gray SA, Polyak CS, Mitchell-Raymundo F, Innis BL, et al. Rapid detection of adenovirus in throat swab specimens by PCR during respiratory disease outbreaks among military recruits. J Clin Microbiol. 2003 Feb. 41(2):810-2. [Medline].

  22. Marchiori E, Escuissato DL, Gasparetto TD, Considera DP, Franquet T. "Crazy-paving" patterns on high-resolution CT scans in patients with pulmonary complications after hematopoietic stem cell transplantation. Korean J Radiol. 2009 Jan-Feb. 10(1):21-4. [Medline]. [Full Text].

  23. Carter BA, Karpen SJ, Quiros-Tejeira RE, et al. Intravenous Cidofovir therapy for disseminated adenovirus in a pediatric liver transplant recipient. Transplantation. 2002 Oct 15. 74(7):1050-2. [Medline].

  24. Hayashi M, Lee C, de Magalhaes-Silverman M. Adenovirus infections in BMT patients successfully treated with cidofovir. Blood. 2000. 96 (suppl 1):189a.

  25. Muller WJ, Levin MJ, Shin YK, Robinson C, Quinones R, Malcolm J. Clinical and in vitro evaluation of cidofovir for treatment of adenovirus infection in pediatric hematopoietic stem cell transplant recipients. Clin Infect Dis. 2005 Dec 15. 41(12):1812-6. [Medline].

  26. Neofytos D, Ojha A, Mookerjee B, Wagner J, Filicko J, Ferber A, et al. Treatment of adenovirus disease in stem cell transplant recipients with cidofovir. Biol Blood Marrow Transplant. 2007 Jan. 13(1):74-81. [Medline].

  27. Yusuf U, Hale GA, Carr J, Gu Z, Benaim E, Woodard P. Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation. 2006 May 27. 81(10):1398-404. [Medline].

  28. Wy Ip W, Qasim W. Management of adenovirus in children after allogeneic hematopoietic stem cell transplantation. Adv Hematol. 2013. 2013:176418. [Medline]. [Full Text].

  29. Saquib R, Melton LB, Chandrakantan A, Rice KM, Spak CW, Saad RD, et al. Disseminated adenovirus infection in renal transplant recipients: the role of cidofovir and intravenous immunoglobulin. Transpl Infect Dis. 2009 Sep 15. [Medline].

  30. Feuchtinger T, Lücke J, Hamprecht K, Richard C, Handgretinger R, Schumm M. Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation. Br J Haematol. 2005 Feb. 128(4):503-9. [Medline].

  31. Fanourgiakis P, Georgala A, Vekemans M, Triffet A, De Bruyn JM, Duchateau V. Intravesical instillation of cidofovir in the treatment of hemorrhagic cystitis caused by adenovirus type 11 in a bone marrow transplant recipient. Clin Infect Dis. 2005 Jan 1. 40(1):199-201. [Medline].

  32. Barraza EM, Ludwig SL, Gaydos JC et al. Reemergence of adenovirus type 4 acute respiratory disease in military trainees:report of an outbreak during a lapse in vaccination. J Infect Dis. June 1999. 179:1531-3. [Medline].

  33. Ryan MA, Gray GC, Smith B, et al. Large epidemic of respiratory illness due to adenovirus types 7 and 3 in healthy young adults. Clin Infect Dis. 2002 Mar 1. 34(5):577-82. [Medline].

  34. Vora GJ, Lin B, Gratwick K et al. o-infections of adenovirus species in previously vaccinated patients. Emerg Infect Dis. June 2006. 12:921-30. [Medline].

  35. Rutala WA, Peacock JE, Gergen MF, Sobsey MD, Weber DJ. Efficacy of hospital germicides against adenovirus 8, a common cause of epidemic keratoconjunctivitis in health care facilities. Antimicrob Agents Chemother. 2006 Apr. 50 (4):1419-24. [Medline].

  36. CDC. Acute Respiratory Disease Associated with Adenovirus Serotype 14 --- Four States, 2006--2007. MMWR Weekly. November 16, 2007. 56:[Full Text].

  37. Sander DM. The Big Picture Book of Viruses: Adenoviridae. 1995. Available at: http://www.tulane.edu/~dmsander/Big_Virology/BVDNAadeno.html. [Full Text].

 
Previous
Next
 
A virus image from the International Committee on Taxonomy of Viruses, in The Big Picture Book of Viruses, available at http://www.virology.net/Big_Virology/BVDNAadeno.html.
Transmission electron micrograph of adenovirus. Image courtesy of the US Centers for Disease Control and Prevention.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.