- Visualisation of Chikungunya Virus Replication Complex on Cell Membrane Nanostructures
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Abstract:
- This is an IDR-URECA project which aims to study the Chikungunya virus replication complex using a newly developed nano-platform. As an interdisciplinary research project, it allows me to explore my interests in both molecular biology and nanotechnology. Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes infection with symptoms of fever and joint pain. There is currently no approved antiviral treatment available. One of the potential drug targets is the viral replication complex (RC) formed inside the host cells. It appears in a bulb-shaped nanoscale membrane invagination called “spherule”. Four nonstructural proteins (nsPs) from the same viral polyprotein (P1234) are needed for RC assembly. However, their structural arrangement in RC is poorly understood, which poses a challenge in drug development. In this study, we utilised a newly developed nano-platform to induce defined curvature on cell plasma membrane and probed whether membrane invagination impacted the assembly of viral proteins. Specifically, we constructed viral protein nsP1 and its membrane binding deficiency mutant with green fluorescent proteins (GFPs), as well as polyprotein P1234 without proteolytic processing. After transfecting in U2OS cells, nsP1 showed preferential accumulation on nanobar-curved membrane sites comparing to its mutant and pre-proteolytic polyproteins, which indicated a pivotal role of nsP1 in spherule formation. In addition, we demonstrated that nanostructures could serve as a new platform to probe membrane-associated viral protein assembly. More information can be uncovered using this platform to facilitate the development of antiviral drugs against CHIKV infection.
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