Project 460499

Viral infectious diseases pose a great threat to public health and the global economy. The majority are caused by emerging viruses that originated from animals and infect humans. According to a report from the World Health Organization, these viruses are emerging at a rate that has not been seen in the past decade due to population growth and climate change. Therefore, it is urgent to develop intervention strategies against emerging viral diseases. To achieve this, we need to understand the fundamental mechanisms of how viruses infect cells and how the cell intrinsic immunity defense the infection of novel viruses. Many newly emerged viruses are RNA viruses that are coated by a cell-derived, lipid membrane referred to as an envelope. Enveloped viruses enter cells at the cell surface or in endocytic compartments via membrane fusion facilitated by a concerted effort of viral and cellular components. Therefore, membrane fusion has been the target of several intrinsic immune response factors, such as interferon-induced transmembrane proteins (IFITMs), as well as antiviral therapeutics and vaccines. We are investigating how viral and cellular components are recruited and take action at the right place and time to promote and/or inhibit membrane fusion. We will study the entry process of an emerging, deadly paramyxovirus--Nipah virus. We will use super-resolution microscopy to capture the tiny and fast-moving biomolecules on cell membranes and visualize their organization, dynamics, and interactions. In addition, we will use classical mutagenesis, molecular cell biology, and biochemistry tools to elucidate the biological relevance of the single-moleucle organization in virus-induced membrane fusion. This study will provide insights into the fundamental biology of viral entry and inform the design of future antivirals.