Mechanisms of pathogenesis of emerging adenoviruses

Abstract

Periodic outbreaks of human adenovirus infections can cause severe illness in people with no known predisposing conditions. The reasons for this increased viral pathogenicity are uncertain. Adenoviruses are constantly undergoing mutation during circulation in the human population, but related phenotypic changes of the viruses are rarely detected because of the infrequency of such outbreaks and the limited biological studies of the emergent strains. Mutations and genetic recombinations have been identified in these new strains. However, the linkage between these genetic changes and increased pathogenicity is poorly understood. It has been observed recently that differences in virus-induced immunopathogenesis can be associated with altered expression of non-mutant viral genes associated with changes in viral modulation of the host innate immune response. Initial small animal studies indicate that these changes in viral gene expression can be associated with enhanced immunopathogenesis in vivo. Available evidence suggests the hypothesis that there is a critical threshold of expression of certain viral genes that determines both the sustainability of viral transmission in the human population and the enhancement of immunopathogenesis. Studies of this possibility will require extension of the analysis of outbreak viral strains from a sequencing-based focus to biological studies of relationships between viral gene expression and pathogenic responses. Advances in this area will require increased coordination among public health organizations, diagnostic microbiology laboratories, and research laboratories to identify, catalog, and systematically study differences between prototype and emergent viral strains that explain the increased pathogenicity that can occur during clinical outbreaks.

Human adenovirus infections: update and consideration of mechanisms of viral persistence

“…Severity of ARDS is scored based on the level of hypoxemia, and treatment of ARDS is mainly supportive care, with mortality rates of 27–45% [6]. Outbreaks of pneumonia and ARDS are usually caused by HAdV from groups B, C and E HAdV that have newly emerged in the population, as a result of viral mutations or recombination events [7 ▪ ].…”

Respiratory DNA viruses are undetectable in nasopharyngeal secretions from adenotonsillectomized children

“…However, it should be kept in mind that results of lower virus detection rates post-adenotonsillectomy could also have been affected by an overall state of better health and reduced rates of respiratory infections in general in children after tonsillectomy. In addition, in the follow-up HPIV-I 0 (0%) 0 (0%) 1 HPIV-III 0 (0%) 0 (0%) 1 analysis children have become older, and this may have affected age-related susceptibilities to such viruses as HAdV and HBoV, which are generally more common in smaller children and toddlers [5,6,7]. Detection of respiratory viruses in tonsillar tissue is significant, not only because it may complicate laboratory diagnosis of viral ARI, but especially because those tissues can be potential sources of infectious viruses in the community.…”

Introductory Chapter: Human Adenoviruses

“…Among the products of early adenoviral genes are factors that delay the development of apoptosis. In general, this reflects a strategy aimed at improving the survival of infected cells and creating conditions for viral persistence [22].…”