Roles of virus-integrin interactions and rotavirus modulation of host cell responses in viral pathogenesis

轮状病毒是儿童严重胃肠炎的主要原因，并导致每27名澳大利亚5岁以下儿童中就有一人住院。目前还没有轮状病毒疫苗可用。我们的目标是发现轮状病毒如何与宿主细胞相互作用。这些信息对于研制安全有效的疫苗或能够阻止宿主细胞中病毒生长的治疗剂是必要的。以前，我们证明轮状病毒附着在细胞上，并使用存在于细胞表面的整合素蛋白家族的几个成员进入细胞。整合素对细胞的黏附、存活和通讯至关重要。在这个项目中，我们将确定轮状病毒对整合素的使用如何调节细胞功能。这将帮助我们了解轮状病毒如何致病，病毒如何在体内传播，以及免疫反应如何保护我们免受轮状病毒的伤害。轮状病毒使用特定的蛋白质序列片段与整合素结合，我们已经证明，这些蛋白质序列也存在于导致肝炎、艾滋病和麻疹的其他人类病毒病原体中。我们将确定这些其他病毒是否也识别整合素。

Rotaviruses are the main cause of severe gastroenteritis in children, and cause 1 in 27 Australian children under the age of 5 years to spend time in hospital. There is currently no rotavirus vaccine available. We aim to discover how rotavirus interacts with host cells. This information is necessary to formulate a safe and effective vaccine, or a therapeutic agent that can block virus growth in host cells. Previously, we showed that rotavirus attaches to cells and enters them using several members of the integrin protein family that are present on the surface of the cells. Integrins are critical for cell adhesion, survival and communication. In this project, we will identify how rotavirus usage of integrins modulates cell functions. This will help us understand how rotavirus causes disease, how virus spreads in the body and how the immune response defends us from rotavirus. Rotavirus binds integrins using particular stretches of protein sequence that we have shown are also present in other human viral pathogens that cause hepatitis, AIDS and measles. We will determine if these other viruses also recognize integrins.