Virology. 2013 Sep;444(1-2):181-90.

The intermediate filament network protein, vimentin, is required for parvoviral infection.

Fay N, Panté N.

Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z4.


Intermediate filaments (IFs) have recently been shown to serve novel roles during infection by many viruses. Here we have begun to study the role of IFs during the early steps of infection by the parvovirus minute virus of mice (MVM). We 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, we found that vimentin plays an important role in the life cycle of MVM. The number of cells, which successfully replicated MVM, was reduced in infected cells in which the vimentin network was genetically or pharmacologically modified; viral endocytosis, however, remained unaltered. Perinuclear accumulation of MVM-containing vesicles was reduced in cells lacking vimentin. Our data suggests that vimentin is required for the MVM life cycle, presenting possibly a dual role: (1) following MVM escape from endosomes and (2) during endosomal trafficking of MVM.

KEYWORDS: Endosomal trafficking, Intermediate filaments, Minute virus of mice, Parvovirus, Vimentin

PMID: 23838001



The field of virology is rapidly changing along with viruses themselves. Hence, studying the cellular mechanisms used by viruses is gaining interest as a mode for novel antiviral therapeutics which target cellular mechanisms rather than viral proteins. Currently, there is a lack of information about the role of intermediate filaments (IFs) during viral infection. In general, among the cellular cytoskeleton components, IFs are heavily understudied. One reason for this is that there are currently no commercially available inhibitors for IFs. However, acrylamide (ACR) has been used to disrupt the IF network. Cells treated with ACR show the IF network forming aggregates and eventually collapse using indirect immunofluorescence microscopy [1].

IFs have long been known to serve scaffolding functions within the cell, and recently, additional functions have been elucidated (reviewed in [2]). Many viruses, such as African Swine Fever Virus, HIV-1, and Human Cytomegalovirus have been shown to require the IF network protein, vimentin, for a successful infection (reviewed in [3,4]). The role of IFs during viral infection has yet to be characterized for the parvovirus, minute virus of mice (MVM). This rodent parvovirus is non-pathogenic to humans and has the ability to preferentially target and kill rapidly dividing cancer cells. Thus, MVM could be developed for anti-cancer therapy (e.g., to kill tumor cells infected by the virus but not uninfected normal cells). However, before MVM could be used for anti-cancer therapy its interaction with host factors, including IF, must be characterized at the molecular level.

Some of the properties of MVM that make this virus attractive for developing it for delivery of therapeutic genes for human gene therapy are its small size and genetic simplicity. Parvoviruses are non-enveloped, icosahedral viruses that are 26-30 nm in diameter, and contain a single-stranded linear 5 kb DNA genome. One trait that makes parvoviruses unique from other viruses is their small size and single stranded DNA genome. In addition, MVM replication and genome composition are very well characterized (reviewed in [5,6]). Parvoviruses use a variety of cellular mechanisms for successful cell infection, from endocytosis to initiation of replication (reviewed in [5,7,8]).

In this study we characterized the role of IFs in the life cycle of MVM. We found that MVM requires the vimentin network for successful infection and have established the foundation to answer several pertinent questions regarding the use of the IF network by MVM. We first characterized the effects of MVM infection on the vimentin network. We found that during early infection with MVM, the vimentin network was considerably altered, yielding collapsed immunofluorescence staining of vimentin, which accumulated on one side of the nucleus in close proximity to the virus (see Figure 1). In addition to these rearrangements, we found that vimentin seems to play an important role in the life cycle of MVM, as the expression of the viral nonstructural protein 1 (NS1) was reduced in infected cells in which the vimentin network was modified, either genetically or pharmacologically with the use of ACR. We showed that this was not due to a reduction of cell entry of the virus, or a defect in the cell cycle of these modified cells, but rather to a defect in late endosome/lysosome position as the perinuclear accumulation of MVM-containing vesicles was reduced in cells lacking vimentin. We concluded that an intact vimentin network is required for efficient trafficking of MVM-containing vesicles and ultimately MVM replication.

By studying the mechanisms for successful infection employed by MVM we will increase our understanding of the extent to which viruses may take advantage of host mechanisms to increase the efficiency and spread of infection.


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biomedical-frontiers-figureFig 1. Vimentin is rearranged and required during MVM infection. We have shown that in comparison to mock-infection (a), the vimentin network was rearranged during infection with MVM (b), yielding similar vimentin network rearrangement as that induced by ACR (c). The cell diagram indicates this result. The three images were obtained by confocal microscopy of mouse fibroblast cells mock infected (a) or infected with MVM (b). For (c), cells were treated with 5 mM ACR. Cells were labeled with an anti-vimentin antibody (green), an anti-MVM capsid antibody (red), and with DAPI to detect DNA (blue). Scale bars, 10 µm.

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