关键词: diarrhea glycans histo-blood group antigens probiotics rotavirus infection shedding

Mesh : Animals Antibodies, Viral / immunology blood Bacteria / immunology Blood Group Antigens / immunology Cytokines / metabolism Diarrhea / prevention & control virology Germ-Free Life Immunoglobulin A / immunology Rotavirus / immunology Rotavirus Infections / immunology virology Swine Swine Diseases / immunology virology Virus Shedding

来  源:   DOI:10.3390/v16050660   PDF(Pubmed)

Abstract:
The suboptimal performance of rotavirus (RV) vaccines in developing countries and in animals necessitates further research on the development of novel therapeutics and control strategies. To initiate infection, RV interacts with cell-surface O-glycans, including histo-blood group antigens (HBGAs). We have previously demonstrated that certain non-pathogenic bacteria express HBGA- like substances (HBGA+) capable of binding RV particles in vitro. We hypothesized that HBGA+ bacteria can bind RV particles in the gut lumen protecting against RV species A (RVA), B (RVB), and C (RVC) infection in vivo. In this study, germ-free piglets were colonized with HBGA+ or HBGA- bacterial cocktail and infected with RVA/RVB/RVC of different genotypes. Diarrhea severity, virus shedding, immunoglobulin A (IgA) Ab titers, and cytokine levels were evaluated. Overall, colonization with HBGA+ bacteria resulted in reduced diarrhea severity and virus shedding compared to the HBGA- bacteria. Consistent with our hypothesis, the reduced severity of RV disease and infection was not associated with significant alterations in immune responses. Additionally, colonization with HBGA+ bacteria conferred beneficial effects irrespective of the piglet HBGA phenotype. These findings are the first experimental evidence that probiotic performance in vivo can be improved by including HBGA+ bacteria, providing decoy epitopes for broader/more consistent protection against diverse RVs.
摘要:
轮状病毒(RV)疫苗在发展中国家和动物中的性能欠佳,因此需要对新型疗法和控制策略的开发进行进一步研究。要开始感染,RV与细胞表面O-聚糖相互作用,包括组织血型抗原(HBGA)。我们先前已经证明某些非致病性细菌表达能够在体外结合RV颗粒的HBGA-样物质(HBGA+)。我们假设HBGA+细菌可以结合肠腔中的RV颗粒,保护免受RV物种A(RVA),B(RVB),和体内C(RVC)感染。在这项研究中,无菌仔猪用HBGA或HBGA-细菌混合物定植,并用不同基因型的RVA/RVB/RVC感染。腹泻的严重程度,病毒脱落,免疫球蛋白A(IgA)Ab滴度,和细胞因子水平进行评估。总的来说,与HBGA-细菌相比,HBGA+细菌定植导致腹泻严重程度降低和病毒脱落。与我们的假设一致,RV疾病和感染的严重程度降低与免疫反应的显著改变无关.此外,无论仔猪HBGA表型如何,HBGA细菌定植都具有有益作用。这些发现是第一个实验证据,包括HBGA+细菌可以改善体内益生菌性能,提供诱饵表位用于针对不同RV的更广泛/更一致的保护。
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