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Published on: November 12, 2015
Persistence and reactivation of human adenoviruses in the gastrointestinal tract
Insights
Persistent human adenoviruses (HAdVs) in the pediatric gastrointestinal tract, particularly the terminal ileum, can lead to dangerous infections in immunocompromised children undergoing stem cell transplants.
Area of Science:
- Virology
- Immunology
- Gastroenterology
Background:
- Persistent human adenoviruses (HAdVs) pose significant risks, including high morbidity and mortality, in pediatric hematopoietic stem cell transplant (HSCT) recipients.
- The gastrointestinal (GI) tract is a primary source of invasive HAdV infections, but the exact locations of HAdV persistence remain unclear.
Purpose of the Study:
- To investigate the sites of HAdV persistence within the pediatric GI tract.
- To determine the correlation between pre-transplant intestinal HAdV shedding and the risk of invasive infection post-transplant.
Main Methods:
- Prospective screening of GI biopsies from 143 non-HSCT pediatric patients.
- Monitoring of serial stool specimens from 148 pediatric HSCT recipients using real-time PCR.
- In situ hybridization and immunohistochemistry to identify HAdV presence in specific GI tissues.
Main Results:
- HAdV persistence in the GI tract was detected in 31% of pediatric patients, with the highest prevalence in the terminal ileum.
- HAdV was identified in lymphoid cells of the lamina propria, indicating persistence in these cells.
- High levels of replicating HAdV were found in intestinal epithelial cells of some transplant recipients.
- Pre-transplant intestinal HAdV shedding correlated with an increased risk of invasive HAdV infection post-transplant.
Conclusions:
- The pediatric GI tract serves as a reservoir for HAdV persistence and reactivation, particularly within intestinal lymphocytes.
- The intestinal epithelium is a key site for viral replication preceding dissemination and invasive infections.
- Findings are crucial for assessing the risk of life-threatening invasive HAdV infections in immunocompromised children.
Abstract:
Reactivation of persistent human adenoviruses (HAdVs) is associated with high morbidity and mortality in paediatric haematopoietic stem cell transplant (HSCT) recipients. Although invasive HAdV infections mainly arise from the gastrointestinal (GI) tract, the specific sites of HAdV persistence are not well characterised. We prospectively screened biopsies from 143 non-HSCT paediatric patients undergoing GI endoscopy and monitored serial stool specimens from 148 paediatric HSCT recipients for the presence of HAdV by real-time PCR. Persistence of HAdV in the GI tract was identified in 31% of children, with the highest prevalence in the terminal ileum. In situ hybridisation and immunohistochemistry identified HAdV persistence in lymphoid cells of the lamina propria, whereas biopsies from five transplant recipients revealed high numbers of replicating HAdV in intestinal epithelial cells. The prevalence of HAdV species, the frequencies of persistence in the GI tract and reactivations post transplant indicated a correlation of intestinal HAdV shedding pre-transplant with high risk of invasive infection. HAdV persistence in the GI tract is a likely origin of infectious complications in immunocompromised children. Intestinal lymphocytes represent a reservoir for HAdV persistence and reactivation, whereas the intestinal epithelium is the main site of viral proliferation preceding dissemination. The findings have important implications for assessing the risk of life-threatening invasive HAdV infections.
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