Adenovirus as an emerging pathogen in immunocompromised patients

Abstract

Summary Adenoviruses are non‐enveloped, lytic, DNA viruses capable of infecting most animal species. There are 51 different human adenovirus serotypes, which are grouped from A to F on the basis of genome size, composition, homology and organization. Pathogenicity varies according to group and type, but infections are generally well controlled by the host immune system in immunocompetent individuals. However, in the immunosuppressed, adenoviral infections are a frequent cause of morbidity and mortality. To date there is no effective therapy. Adoptive transfer of immune T cells offers a therapeutic option, but this strategy has been hindered by the lack of information on targets of protective cellular immunity, and by the immunological heterogeneity of the 51 human adenoviruses. Nevertheless, until such an approach is implemented, or an effective antiviral agent becomes commercially available, it is likely that adenovirus infections will continue to be responsible for a significant number of virus‐associated deaths each year.

Safe adoptive transfer of virus‐specific T‐cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation

“…The effect of immunosuppression and the successful treatment of severe adenovirus infection with DLI therefore support the rationale for adoptive transfer of adenovirus-specific T cells. Based on these observations, an urgent clinical demand for donor lymphocyte preparations with enriched adenovirusspecific T cells and reduced alloreactivity has been expressed (Leen & Rooney, 2005;Moss & Rickinson, 2005). We have previously described a protocol using the antigen-specific c-interferon (IFN-c) secretion of T cells to isolate adenovirus-reactive T cells (Feuchtinger et al, 2004).…”

The Role of Capsid Maturation on Adenovirus Priming for Sequential Uncoating

“…Adenovirus is a mild pathogen for humans but can become clinically relevant in immunocompromised patients, and it is widely examined as a therapeutic vector (1,2). The large (ϳ950 Å) nonenveloped, pseudo T ϭ 25 icosahedral capsid is assembled from at least 11 different types of proteins.…”

Adenovirus infections in immuncompromised patients

“…E gének termékei a gazdasejt átprogramozásában és a szervezet immunreakcióinak elkerülésében is szerepet játszanak. Ezzel a perzisztens és latens fertőzések is lehetővé válnak [3,4]. A virion szerkezeti fehérjéit a késői gének (late genes, L1-L5) kódolják.…”

“…Fertőzést követően a hexonnal szemben csoportspecifi kus, nem neutralizáló antitestek képződnek, míg a fi ber szerotípus-specifi kus, neutralizáló ellenanyagok képződését váltja ki [2]. Az intracelluláris vírusok eradikációja a celluláris immunreakció közreműködésével történik, és a fertőzött sejtek elpusztítását eredményezi CD4+ és CD8+ T-sejtek által [4]. A fertőzött lymphocytákban episomalis formában fennmaradó vírusgenom latens vagy perzisztens fertő-zést eredményezhet.…”