Replication of Human Norovirus in Mice after Antibiotic-Mediated Intestinal Bacteria Depletion.
Por:
Santiso-Bellon C, Gozalbo-Rovira R, Buesa J, Rubio-Del-Campo A, Pena-Gil N, Navarro-Lleo N, Carcamo-Calvo R, Yebra M, Monedero V, Rodriguez-Diaz J
Publicada:
13 sep 2022
Ahead of Print:
13 sep 2022
Resumen:
Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1-3 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNFa and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators.
Filiaciones:
Santiso-Bellon C:
Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain
Instituto de Investigación INCLIVA, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
Gozalbo-Rovira R:
Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain
Instituto de Investigación INCLIVA, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
Buesa J:
Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain
Instituto de Investigación INCLIVA, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
Rubio-Del-Campo A:
Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Av. Agustín Escardino 7, 46980 Paterna, Spain
Pena-Gil N:
Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain
Instituto de Investigación INCLIVA, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
Navarro-Lleo N:
Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain
Carcamo-Calvo R:
Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Av. Agustín Escardino 7, 46980 Paterna, Spain
Yebra M:
Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Av. Agustín Escardino 7, 46980 Paterna, Spain
Monedero V:
Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Av. Agustín Escardino 7, 46980 Paterna, Spain
Rodriguez-Diaz J:
Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain
Instituto de Investigación INCLIVA, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
Department of Microbiology, School of Medicine, University of Valencia, Av. Blasco Ibanez 17, 46010 Valencia, Spain. Instituto de Investigacion INCLIVA, Hospital Clinico Universitario de Valencia, 46010 Valencia, Spain.
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