Persistence and reactivation of human adenoviruses in the gastrointestinal tract  K. Kosulin, E. Geiger, A. Vécsei, W.-D. Huber, M. Rauch, E. Brenner, F. Wrba, K. Hammer, A. Innerhofer, U. Pötschger, A. Lawitschka, S. Matthes-Leodolter, G. Fritsch, T. Lion  Clinical Microbiology and Infection  Volume 22, Issue 4, Pages 381.e1-381.e8 (April 2016) DOI: 10.1016/j.cmi.2015.12.013 Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 1 Distribution of human adenovirus (HAdV) persistence within the gastrointestinal (GI) tract. A total of 576 biopsies from the GI tract were analysed for the presence of HAdV DNA in 143 non- haematopoietic stem cell transplant control patients. Frequency of HAdV detection within individual sections of the GI tract is shown, highlighting the ileum as the most prevalent site. Clinical Microbiology and Infection 2016 22, 381.e1-381.e8DOI: (10.1016/j.cmi.2015.12.013) Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 2 In situ hybridisation for human adenovirus (HAdV) DNA on biopsy specimens from the gastrointestinal (GI) tract. The top panels (a–c) show representative findings in biopsies from the terminal ileum obtained from non-haematopoietic stem cell transplant (non-HSCT) control individuals with HAdV persistence displaying scattered signals in lymphoid cells of the lamina propria. A signal in an epithelial cell, rarely observed in patients with persistent virus, is shown in (a) (arrow). The central panels (d–f) represent biopsies derived from HAdV-positive transplant recipients showing dense hybridisation signals within epithelial cells and scattered signals in restricted areas of the lamina propria (f). The bottom panels represents positive (g) and negative (h) hybridisation controls, respectively. (c, f: 100× magnification, all others: 400×.) Clinical Microbiology and Infection 2016 22, 381.e1-381.e8DOI: (10.1016/j.cmi.2015.12.013) Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 3 Immunohistochemical detection of human adenovirus (HAdV) protein expression. (a, b) Ileum biopsies from HAdV-positive non-haematopoietic stem cell transplant (non-HSCT) individuals revealing positive signals in interstitial lymphoid cells in one patient (a) and absence of any detectable viral protein expression in another patient (b). (c, d) Representative biopsies from two HAdV-positive transplant recipients with strong signals of viral protein expression in epithelial cells. (All panels: 400× magnification.) Clinical Microbiology and Infection 2016 22, 381.e1-381.e8DOI: (10.1016/j.cmi.2015.12.013) Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 4 Distribution of human adenovirus (HAdV) species in the gastrointestinal (GI) tract. (a–c) Relative prevalence of persistent HAdV species detected in biopsies from the jejunum (a), ileum (b) and colon (c), which displayed the highest frequency of virus positivity among the sections of the gastrointestinal (GI) tract analysed. (d) Similar overall occurrence of different HAdV species in tissue biopsies from the GI tract in non-haematopoietic stem cell transplant (non-HSCT) paediatric patients with viral persistence (black columns) in comparison with stool specimens in children after allogeneic HSCT (grey columns). Clinical Microbiology and Infection 2016 22, 381.e1-381.e8DOI: (10.1016/j.cmi.2015.12.013) Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. S1 Correlation between human adenovirus frequency and patient age in the non-haematopoietic stem cell transplant control group. Copy numbers of different human adenovirus species in biopsies from the gastrointestinal tract.2 Clinical Microbiology and Infection 2016 22, 381.e1-381.e8DOI: (10.1016/j.cmi.2015.12.013) Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions