a method for quantifying mechanical properties of tissue following viral infection一种量化的方法病毒感染后力学性能的组织.pdfVIP

A Method for Quantifying Mechanical Properties of Tissue following Viral Infection Vy Lam1,3, Tarin Bigley1,2, Scott S. Terhune1,2*, Tetsuro Wakatsuki1,3,4 1 Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America, 2 Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America, 3 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America, 4 InvivoSciences LLC, Madison, Wisconsin, United States of America Abstract Viral infection and replication involves the reorganization of the actin network within the host cell. Actin plays a central role in the mechanical properties of cells. We have demonstrated a method to quantify changes in mechanical properties of fabricated model three-dimensional (3D) connective tissue following viral infection. Using this method, we have characterized the impact of infection by the human herpesvirus, cytomegalovirus (HCMV). HCMV is a member of the herpesvirus family and infects a variety of cell types including fibroblasts. In the body, fibroblasts are necessary for maintaining connective tissue and function by creating mechanical force. Using this 3D connective tissue model, we observed that infection disrupted the cell’s ability to generate force and reduced the cumulative contractile force of the tissue. The addition of HCMV viral particles in the absence of both viral gene expression and DNA replication was sufficient to disrupt tissue function. We observed that alterations of the mechanical properties are, in part, due to a disruption of the underlying complex actin microfilament network established by the embedded fibroblasts. Finally, we were able to prevent HCMV-mediated