Ramani Sasirekha, Hu Liya, Venkataram Prasad B V, Estes Mary K
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas.
Cell Mol Gastroenterol Hepatol. 2016 Mar 12;2(3):263-273. doi: 10.1016/j.jcmgh.2016.03.002. eCollection 2016 May.
Interaction with cellular glycans is a critical initial step in the pathogenesis of many infectious agents. Technological advances in glycobiology have expanded the repertoire of studies delineating host glycan-pathogen interactions. For rotavirus, the VP8* domain of the outer capsid spike protein VP4 is known to interact with cellular glycans. Sialic acid was considered the key cellular attachment factor for rotaviruses for decades. Although this is true for many rotavirus strains causing infections in animals, glycan array screens show that many human rotavirus strains bind nonsialylated glycoconjugates, called , in a strain-specific manner. The expression of histo-blood group antigens is determined genetically and is regulated developmentally. Variations in glycan binding between different rotavirus strains are biologically relevant and provide new insights into multiple aspects of virus pathogenesis such as interspecies transmission, host range restriction, and tissue tropism. The genetics of glycan expression may affect susceptibility to different rotavirus strains and vaccine viruses, and impact the efficacy of rotavirus vaccination in different populations. A multidisciplinary approach to understanding rotavirus-host glycan interactions provides molecular insights into the interaction between microbial pathogens and glycans, and opens up new avenues to translate findings from the bench to the human population.
与细胞聚糖的相互作用是许多感染因子发病机制中的关键起始步骤。糖生物学的技术进步扩大了描绘宿主聚糖-病原体相互作用研究的范围。对于轮状病毒,已知外衣壳刺突蛋白VP4的VP8*结构域与细胞聚糖相互作用。几十年来,唾液酸一直被认为是轮状病毒的关键细胞附着因子。虽然对于许多在动物中引起感染的轮状病毒株来说确实如此,但聚糖阵列筛选表明,许多人类轮状病毒株以菌株特异性方式结合非唾液酸化糖缀合物,称为 。组织血型抗原的表达由基因决定并受发育调控。不同轮状病毒株之间聚糖结合的差异具有生物学相关性,并为病毒发病机制的多个方面提供了新见解,如种间传播、宿主范围限制和组织嗜性。聚糖表达的遗传学可能影响对不同轮状病毒株和疫苗病毒的易感性,并影响轮状病毒疫苗在不同人群中的效力。一种理解轮状病毒-宿主聚糖相互作用的多学科方法为微生物病原体与聚糖之间的相互作用提供了分子见解,并开辟了将实验室研究结果转化应用于人类群体的新途径。