Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Abstract

The cellular cytoskeleton is central for key cellular functions, and as such is a marker for diseased and infected cell states. Here we analyzed infection with rubella virus (RV) strains with respect to phenotypes in cellular mechanical properties, cell movement, and viral cytopathogenicity. Real-time deformability cytometry (RT-DC), as a high-throughput platform for the assessment of cell mechanics, revealed a correlation of an increase in cortical filamentous-actin (F-actin) with a higher cellular stiffness. The additional reduction of stress fibers noted for only some RV strains as the most severe actin rearrangement lowered cell stiffness. Furthermore, a reduced collective and single cell migration speed in a wound healing assay was detected in addition to severe changes in cell morphology. The latter was followed by activation of caspase 3/7 as a sign for induction of apoptosis. Our study emphasizes RT-DC technology as a sensitive means to characterize viral cell populations and to implicate alterations of cell mechanical properties with cell functions. These interdependent events are not only promising options to elucidate viral spread and to understand viral pathologies within the infected host. They also contribute to any diseased cell state, as exemplified by RV as a representative agent for cytoskeletal alterations involved in a cytopathological outcome.

Natural killer cell immune synapse formation and cytotoxicity are controlled by tension of the target interface

“…However, a significant decrease in stiffness is correlated with metastatic potential, with one study having found a 73% reduction in stiffness following metastasis ( Cross et al, 2007 ; Guck et al, 2005 ; Hou et al, 2009 ). Viral infection also induces cortical actin restructuring, with one strain of rubella virus accounting for an increase of 17.8% in Young's modulus, a measure of substrate stiffness ( Kräter et al, 2018 ). Thus, stiffening or softening of cells within tissues may be indicative of transformation.…”

Hsp70 Is a Potential Therapeutic Target for Echovirus 9 Infection

“…While viruses are obligate intracellular parasites that have a life cycle requiring the engagements and modification of cytoskeleton at all stages, from invasion through replication to budding and transmission. By far, lots of viruses have been reported that evolved to engage and subvert the cytoskeleton proteins' function, such as RSV (Shahriari et al, 2016 ), Dengue Virus (Wang et al, 2010 ), Rubella virus (Krater et al, 2018 ), avian influenza viruses (Guo et al, 2018 ), rabies virus (Monroy-Gomez et al, 2018 ), Rhinovirus (Michi and Proud, 2018 ). In the present study, the microtubule-associated proteins Tubb5, Tuba3, the intermediate filament proteins Prph, Vim, and microfilament-associated protein Capza1 were down-regulated by echovirus infection, while microfilament-associated protein Actb and keratin-associated protein Krt83 were up-regulated.…”

Capturing Neonatal Cardiomyocyte – Endothelial interactions on-a-Chip

“…In each experiment 3 region of interest (ROI) was selected for quantification analysis (Figure 1 B) . Euclidean distance [74] or displacement [75,76] was defined as the linear shortest distance between start and end point of a single cell trajectory (Figure 1 A-iv).…”