Microbiota depletion promotes human rotavirus replication in an adult mouse model
Summary The study of human rotavirus (RV) infectivityin vivohas been limited by the lack of small animal models able to efficiently replicate the principal human RV genotypes. In recent years, intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of developing an adult mouse infection model for RV we performed faecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. Contrarily to control mice, in the FMT group, but also in antibiotic-treated mice without FMT, challenge with the human RV G1P[8] genotype, Wa strain (RVwa), resulted in viral shedding in the faeces for 6 days. RV titres in faeces were also significantly higher in antibiotic-treated animals with or without FMT. This excluded the hypothesis that donor’s microbiota promoted infection. Antibiotic treatment followed by self-FMT resulted in incomplete re-establishment of mouse microbiota which partially restored suppression of RVwainfection. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members ofLactobacillus, Bilophila, MucispirillumandOscillospira, reappeared after self-FMT. In antibiotic-treated and FMT animals, differences were observed in gene expression of immune mediators such as IL10, TNF-α and IFNγ and the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human RV infectivity in mice. Viral permissiveness could involve changes in the innate immune system at the small intestine and alterations in the bacteria population that potentially interact with RV, creating a favourable environment for human RV replication in mice..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 24. Dez. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gozalbo-Rovira, Roberto [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2021.04.15.439998 |
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| PPN (Katalog-ID): |
XBI02035469X |
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| 245 | 1 | 0 | |a Microbiota depletion promotes human rotavirus replication in an adult mouse model |
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| 520 | |a Summary The study of human rotavirus (RV) infectivityin vivohas been limited by the lack of small animal models able to efficiently replicate the principal human RV genotypes. In recent years, intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of developing an adult mouse infection model for RV we performed faecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. Contrarily to control mice, in the FMT group, but also in antibiotic-treated mice without FMT, challenge with the human RV G1P[8] genotype, Wa strain (RVwa), resulted in viral shedding in the faeces for 6 days. RV titres in faeces were also significantly higher in antibiotic-treated animals with or without FMT. This excluded the hypothesis that donor’s microbiota promoted infection. Antibiotic treatment followed by self-FMT resulted in incomplete re-establishment of mouse microbiota which partially restored suppression of RVwainfection. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members ofLactobacillus, Bilophila, MucispirillumandOscillospira, reappeared after self-FMT. In antibiotic-treated and FMT animals, differences were observed in gene expression of immune mediators such as IL10, TNF-α and IFNγ and the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human RV infectivity in mice. Viral permissiveness could involve changes in the innate immune system at the small intestine and alterations in the bacteria population that potentially interact with RV, creating a favourable environment for human RV replication in mice. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Santiso-Bellón, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Buesa, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a del Campo, Antonio Rubio |e verfasserin |4 aut | |
| 700 | 1 | |a Vila-Vicent, Susana |e verfasserin |4 aut | |
| 700 | 1 | |a Muñoz, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Yebra, María J. |e verfasserin |4 aut | |
| 700 | 1 | |a Monedero, Vicente |e verfasserin |4 aut | |
| 700 | 1 | |a Rodríguez-Díaz, Jesús |e verfasserin |4 aut | |
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