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Parvoviral interactions with the cytoskeleton : exposing vimentin – the forgotten player

University of British Columbia

There are three structurally and functionally distinct cytoskeleton components: actin filaments, microtubules, and intermediate filaments (IFs). Among the three cytoskeleton networks IFs are understudied; consequently, there is a lack of information about the role of IFs during early viral infection. IFs have long been known to serve structural functions within the cell, and recently, additional functions have been elucidated, including novel roles during infection by many viruses. During early infection with the parvovirus minute virus of mice (MVM), prior to viral replication, I have found that the virus induces dramatic morphological changes in mouse fibroblast cells. This observed change in the shape of infected cells may be a result of the virus using the host cytoskeleton to aid in the mechanism of intracellular trafficking. Thus, this thesis focuses on MVM and its effects on the cytoskeleton components, especially IFs, during infection. Using fluorescence microscopy techniques, I found that during early infection with MVM, after endosomal escape, the vimentin IF network was considerably altered, yielding collapsed immunofluorescence staining near the nuclear periphery. Furthermore, I found that vimentin plays an important role in the infection cycle of MVM. The number of cells successfully replicating MVM was reduced in infected cells in which the vimentin network was pharmacologically modified or in cells lacking a vimentin network; viral endocytosis, however, remained unaltered. Perinuclear accumulation of MVM-containing vesicles and progression of MVM through the endocytic pathway was reduced in cells lacking vimentin. Cells lacking vimentin, accumulated virions in early endosomes up to 2 h post-infection compared to wild type cells. Thus, my data supports a model where vimentin facilitates a productive MVM infection, presenting possibly a dual role: (1) during progression of MVM through the endocytic pathway and (2) following MVM escape from endosomes.

Text

2014-10-09

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/50672

Zoology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/