VI Rulence and Tropism in the Pathogenesis of Adenoviral Respiratory Tract Infection

Human adenoviruses belong to the Adenoviridae family and the Mastadenovirus genus. They are divided into seven species, from A through G. Adenoviruses are medium-sized, nonenveloped, icosahedral viruses of 70 to 90 nm in diameter. Each particle contains a single linear, double-stranded DNA. Adenovirus infections were traditionally associated with respiratory, ocular, or gastrointestinal disease, occurring mainly in children. Over the last years, adenoviruses have increasingly been recognized as significant viral pathogens, with high morbidity and mortality among immunocompromised patients. Different adenovirus serotypes are associated with different disease syndromes. Although most infections are self-limiting in immunocompetent patients, disseminated adenovirus can cause severe or lethal infections in neonates and bone marrow and renal and liver transplant recipients. Serotype identification is critical for epidemiological surveillance, the detection of new strains, assessment of treatment efficacy, and understanding the pathogenesis of adenovirus that often have quite different geographical distributions and associated virulence. In addition, the infection pathway of adenovirus is different based on adenovirus serotypes and target cell type being infected. Most adenovirus, except species B uses coxsackie- adenovirus receptor (CAR) as the first step of intracellular trafficking. Other cellular receptors identified include CD46, CD80, CD86 and integrin. The tissue tropism of different genotype adenovirus may influence the clinical manifestations and infections. Molecular determination of viral component and its interaction between target cells could help to resolve the association of tissue tropism and viral virulence. Once adenovirus internalized within host cells, series of inflammatory cascade will be activated, which include inflammasome formation and MAPK pathway. Although immune reaction in response to adenovirus infection is crucial for viral clearance, robust inflammatory cytokine production may also lead to tissue damage and clinical diseases. Insight into disease based inflammatory response is warranted. Here, in present study, we aim to evaluate the adenoviral virulence and its associated cell tropism and subsequent immune response from clinical based disease model. Also, we will establish the adenovirus respiratory tract infectious animal model and exam the immunopathogenesis in vivo.