title: Anisotropic cell-to-cell spread of vaccinia virus on microgrooved substrate.
abstract: Cell-to-cell spread of virus is a comprehensive process with involvement of cellular actin cytoskeleton and substrate topography can affect the arrangement of cytoskeleton via contact guidance, yet interaction among virus, cytoskeleton and substrate topography is still unknown. To investigate the virus-cell-substrate interaction, we designed a microgrooved poly(dimethyl siloxane) (PDMS) substrate for the study of vaccinia virus (VACV) cell-to-cell spread and the remodeling of cellular actin cytoskeleton in viral infection process. Interestingly, VACV-induced plaques on microgrooved substrate were elliptical instead of circular plaques on smooth substrate, suggesting an anisotropic cell-to-cell spread of VACV. The spread rate was faster in the direction parallel to microgroove and slower in the direction perpendicular to microgroove than that on smooth substrate. Host cells cultured on microgrooved surface showed significant alignment and elongation in the axis parallel to microgrooves. Cell elongation is one reason for anisotropic spread but could not totally explain the phenomenon. Actin fibers in infected cells maintained alignment and VACV-induced actin tails tipped with virions were oriented along the direction parallel to microgroove. These results suggested that substrate topography can affect infected cells and these effects will guide the spread of virus via orientation of actin cytoskeleton. This work opens a window for understanding virus response to substrate topography, and has potential implications on revealing virus-cell-substrate interactions in vivo.
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, State Key Laboratory of Virology, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Xu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, State Key Laboratory of Virology, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, State Key Laboratory of Virology, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Dai-Wen
authors.initials: DW
authors.lastname: Pang
authors.affiliation: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, State Key Laboratory of Virology, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China. Electronic address: zlzhang@whu.edu.cn.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D018625:Microscopy, Atomic Force; D014616:Vaccinia virus / Q000502:physiology*; D014709:Vero Cells
chemical_list: D000199:Actins
keywords: Cell-to-cell spread; Contact guidance; Cytoskeleton; Microfabrication technology; Vaccinia virus