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

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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.