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Intestinal HAdV Infection: Tissue Specificity, Persistence, and Implications for Antiviral Therapy
1Molecular Microbiology, Children's Cancer Research Institute, Zimmermannplatz 10, 1090 Vienna, Austria. karin.kosulin@ccri.at.
Insights
Human adenovirus (HAdV) causes childhood infections. This review explores intestinal HAdV tropism, persistence, and recombination, crucial for understanding pediatric stem cell transplant infections and developing new therapies.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Human adenovirus (HAdV) causes diverse childhood infections, with tissue tropism dictating clinical outcomes.
- Intestinal HAdV infections are significant in pediatric stem cell transplant (SCT) recipients, often preceding clinical symptoms and linked to mortality.
- Antiviral strategies involving interferons may influence HAdV persistence, particularly the repression of the E1A gene.
Purpose of the Study:
- To review intestinal human adenovirus (HAdV) infections, focusing on tissue tropism, persistence, and recombination.
- To discuss the implications of persistent intestinal HAdV in pediatric SCT recipients and the need for further investigation into reactivation and therapy.
- To highlight the emergence of novel recombinant HAdV types in the gut and explore their origins.
Main Methods:
- Literature review of studies on human adenovirus (HAdV) tropism, persistence, and recombination in the intestinal tract.
- Analysis of existing data on HAdV infections in pediatric stem cell transplant recipients.
- Discussion of in-vitro models for studying HAdV-host interactions.
Main Results:
- Specific HAdV species exhibit distinct tissue tropisms, influencing disease presentation.
- Mechanisms of HAdV entry and resistance to immune factors in the intestine are being elucidated.
- Persistent intestinal HAdV infections, especially in immunocompromised children, pose significant clinical challenges.
Conclusions:
- Understanding intestinal HAdV tropism, persistence, and recombination is critical for managing pediatric infections.
- Further research into HAdV reactivation in pediatric SCT recipients is needed to identify effective therapeutic strategies.
- Novel in-vitro models are essential for advancing knowledge of HAdV-host interactions and developing new treatments.
Abstract:
Human adenovirus (HAdV) causes infections predominantly in early childhood and the tissue tropism of specific HAdV species determines the clinical manifestation, including infections of the gastrointestinal tract, respiratory tract, and keratoconjunctivitis. Why HAdV shows such a tropism has not yet been fully elucidated, but in the intestine different mechanisms for virus entry or resistence to immune modulatory factors have been described. Recently identified antiviral strategies by interferons provide evidence about the repression of E1A and maybe even promote HAdV persistence. The presence of HAdV in a persistent status in the gut is of importance in the setting of pediatric stem cell transplant recipients where HAdV detection in stool usually preceds clinical signs and severe infections are related to mortality. The reactivation of persistent intestinal HAdV infections in these patients needs further investigation also with regard to successful therapy options. In addition, several newly identified recombinant HAdV types have been isolated from stool samples, thus raising the question of possible recombination events in the gut. In this review, intestinal HAdV infections are discussed in relation to the tissue tropism, persistence, recombination, and new in-vitro models to enhance the knowledge about virus-host interactions and support the development of new treatment approaches.
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