Viral infection begins when a virus particle breeches the host plasma membrane and successfully delivers its genome into that cell. Though these processes must occur for every viral pathogen that infects a host cell, the entry route can vary depending on the viral pathogen, the host cell type, and the local microenvironmental conditions.
Virus particles are responsive to their environment and use cues from it to adapt and successfully time the entry process into the host cell. It is a continual evolutionary battle between the host and the virus to thwart infection and disease. For example, in SARS Coronavirus-2 (SARS-CoV-2), viral mutation rates frequently outpace the development of technologies used to detect and identify emerging variants of concern (VOC).
Dr. Susan Daniel,
Cornell University
Given the continual emergence of VOC, there is a critical need to develop platforms that can identify the presence of a virus and readily identify its propensity for infection. We built an electronic biomembrane sensing platform that recreates the multifaceted and sequential biological cues that give rise to distinct SARS-CoV-2 virus host cell entry pathways and reports the progression of entry steps of these pathways as electrical signals.
Within these electrical signals, two necessary entry processes mediated by the viral Spike protein, virus binding and membrane fusion, can be distinguished. Most infection ‘on-chip’ devices employ live cells, miniaturized cell cultures or organoid-like structures, which essentially replicate established virology assays in a smaller format. Our device has no living cells and our assay design faithfully replicates the biological cues governing virus response and the selection of distinct entry pathways, mirroring natural occurrences.
We demonstrate that our device captures the fusion function, a critical step in infection that leads to the delivery of the viral genome across the host cell membrane barrier. We can swiftly (in tens of minutes) assess and differentiate the functional traits of VOC. Using this approach, we studied SARS-CoV-2 VOC (Wuhan-Hu-1, Omicron BA.1, and BA.4). We find that these closely related VOC exhibit distinct fusion signatures that correlate with trends reported in cell-based infectivity assays, allowing us to report quantitative differences in fusion characteristics among them that inform their infectivity potentials. This achievement, to our knowledge, marks the first application of a cell-free, virus-free, and label-free system for this purpose.
Dr. Susan Daniel is the Fred H. Rhodes Professor of Chemical Engineering and the William C. Hooey Director of the Robert Frederick Smith School of Chemical and Biomolecular Engineering at Cornell University. Her research team strives to understand phenomena at biological interfaces and chemically patterned surfaces that interact with soft matter – liquids; polymers; and biological materials, like cells, viruses, proteins, and lipids.
Her research is often motivated by human health or advancing biotechnologies for the good of humankind. She is most well known for her work in understanding virus entry and infection; particularly the role of the protein fusion machinery of coronavirus. Her team pioneered “biomembrane chips” to conduct cell- free, biophysical studies of mammalian, bacterial, and plant cell membranes, and recently merged this technology with organic electronic devices for expanded sensing capabilities.
She is an elected fellow of the American Association for the Advancement of Science and the American Institute for Medical and Biological Engineering. She is the recipient of a National Science Foundation CAREER award (2011), the Schwartz Life Sciences award (2016), the College of Engineering’s Research Excellence Award at Cornell University (2017).