Funding outcome

Human parainfluenza virus 3 (HPIV3) is a common respiratory infection in children that can lead to significant disease in vulnerable people. As well, severe respiratory infections in childhood can have lasting impacts health leading to asthma for example, further emphasizing the need for interventions. One of the best targets for therapeutics is viral entry, as stopping a virus from entering the host cell stops infection before it can begin. HPIV3 is a virus so it has proteins on its surface that look like 'spikes' to mediate this process. Most of these virus spike proteins bind to a specific cell protein to trigger virus uptake into the cell so that infection can happen; however, it is unknown which cellular proteins are necessary for HPIV3 infection. The goal of this project is to identify the cellular proteins needed for HPIV3 infection to happen. This type of knowledge can lead to new drugs to treat infections. One such drug called maraviroc is used to prevent human immunodeficiency virus infection of cells. First, we plan to use a purified HPIV3 spike protein to identify the host proteins it prefers to bind to. We will also use a genetic engineering tool called CRISPR to identify cellular genes that are necessary for HPIV3 infection. The cellular genes identified in this experiment will inform further experiments to prove that our proteins of interest make HPIV3 infection happen. Lastly, we plan to support our findings using a mouse model of HPIV3 infection. Together, these experiments will identify the entry receptors for HPIV3, which represent attractive targets for antiviral drug development, reducing the burden of HPIV3 disease in early childhood.