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Adenovirus pathogenesis and vector applications

Authors
Phyllis Flomenberg, MD
Tsoline Kojaoghlanian, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Anna R Thorner, MD

INTRODUCTION

Adenoviruses are lytic, nonenveloped DNA viruses that generally cause a self-limited febrile illness but occasionally can disseminate in immunocompromised hosts and neonates, causing significant morbidity and mortality. Adenoviruses cause pathology during the process of viral replication and lysis of susceptible cells, but these viruses can also cause inflammation in animal models in the absence of viral replication. Thus, the clinical manifestations of adenoviral disease in humans appear to result from both the direct effects of infection and host inflammatory responses.

The pathogenesis of adenovirus infection and the use of this virus as a vector for research applications will be reviewed here. The epidemiology, clinical manifestations, diagnosis, and treatment of adenovirus infection are discussed separately. (See "Epidemiology and clinical manifestations of adenovirus infection" and "Diagnosis, treatment, and prevention of adenovirus infection".)

PATHOGENESIS

Serotype differences — Certain adenovirus serotypes are associated with distinct clinical manifestations, but the basis for these differences is not well understood. As an example, the group C types 1, 2, and 5 are associated with respiratory tract infections; the group B types 11, 34, and 35 cause hemorrhagic cystitis; and the group D types 8, 19, and 37 are the major causes of epidemic keratoconjunctivitis. Serotype-specific clinical manifestations may be partially determined by differences in cell tropism. Some serotypes, for example, display different cell receptor preferences, which are mediated by the viral attachment protein fiber. Although most adenoviruses from groups A, C, D, E, and F bind to the coxsackievirus-adenovirus receptor (CAR), the group B adenoviruses do not bind to this receptor [1]. Group B adenoviruses have been shown to bind to the complement-related protein CD46 as well as CD80 and CD86 (activation markers on hematopoietic cells) [2-4]. After attachment, adenoviruses enter cells via receptor-mediated endocytosis. This internalization process requires interaction of the viral protein penton base with alpha v integrins [5]. Thus, differences in the fiber and penton likely contribute to serotype-specific clinical manifestations. The epidemiology and clinical manifestations of adenovirus infection are discussed separately. (See "Epidemiology and clinical manifestations of adenovirus infection".)

Immune response to adenoviruses — Adenoviruses elicit both innate and adaptive immune responses. Recovery from adenovirus infection is associated with the development of serotype-specific neutralizing antibodies directed mainly at the major capsid protein hexon. Neutralizing antibodies protect against infection with the same serotype of the virus but not against other serotypes. The commercial assays for adenovirus antibodies, such as complement fixation (CF) and enzyme immunoassay (EIA), detect other adenovirus-specific antibodies that cross react with all serotypes. Nearly all adults have serologic evidence of past infection with one or more adenoviruses.

The most important host defense against many viruses, including adenoviruses, is cell-mediated immunity. Fatal adenovirus infections occur most commonly in immunocompromised patients, especially those with defects in cell-mediated immunity [6-8]. Adenovirus-specific memory CD4+ T cells can be detected in most healthy adults and can exhibit cross-reactivity against different serotypes [9]. As an example, a specific CD4+ T cell epitope on the hexon is highly conserved among different serotypes and is recognized by 75 percent of healthy individuals [10]. Adenovirus-specific CD8+ cytotoxic T lymphocytes (CTLs) are detected at lower frequencies, some of which also target conserved epitopes [11,12].

             

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Literature review current through: Nov 2016. | This topic last updated: Mon Sep 28 00:00:00 GMT 2015.
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