In situ structural and functional characterisation of chikungunya virus NSP1: unveiling the mechanism of cell-to-cell viral transmission

• Main Author: Elsen, Kain Elisabeth Franciscus van den
• Other Authors: Luo Dahai
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Medicine, Health and Life Sciences
• Online Access: https://hdl.handle.net/10356/180039
• Institution: Nanyang Technological University

Positive-sense RNA viruses, including coronaviruses, flaviviruses, and alphaviruses, pose significant public health threats due to their rapid spread and disease-causing capabilities. Chikungunya virus (CHIKV), a mosquito-borne pathogen, inflicts severe and debilitating arthralgia in humans, causing substantial morbidity. Many patients endure chronic symptoms long after infection. The global emergence of CHIKV has accelerated due to the expanding range of its vectors driven by climate change. CHIKV’s nonstructural protein 1 (NSP1) triggers host cell protrusions, facilitating efficient virion transmission between cells while evading immune surveillance. Despite extensive research on CHIKV, the molecular basis of these protrusions remains elusive. This study employs in-situ Cryo-ET, super-resolution live-cell imaging, and cell-signalling modulation to investigate NSP1-induced protrusion morphology and molecular basis. Our findings uncover the structure and organisation of NSP1, actin, and ribosomes, key components of these structures. This comprehensive understanding sheds new light on the mechanisms governing viral cell-to-cell transmission, paving the way for innovative antiviral strategies.