Virus logistics – vimentin is required for parvovirus infection
Parvoviruses have always been a bit of a mystery because they are very fussy about the types of cell they will grow in. Mostly, that has been explained as needing actively-dividing cells which are passing through S phase of the cell cycle so that the virus can replicate its DNA genome along with that of the host cell. But maybe that’s not the full story.
The cytoskeleton – a network of cellular scaffolding – is more complicated than you might think. Although it just seems like just a bunch of microscopic fibres, it has multiple important tasks, giving cells their shape, allowing them to move and acting as the transport network of the cell, shifting “stuff” (technical term there) from one place to another. the reason it is able to perform these varied jobs is because it consists of not just one but a variety of different types of filaments – actin, lamins, etc. One of the so-called intermediate filaments is vimentin, which has an important transport role in the cytoplasm.
Working with a mouse parvovirus (MVM) often used for laboratory studies of this virus group, a new paper in Virology shows that disrupting the vimentin part of the cytoskeleton inhibits virus replication. This seems to be because the virus is affected just after it has escaped from endosomes shortly after uptake into host cells, but also because new virus particles fail to accumulate near the nucleus as they normally do. Both of these blockages point to the role of vimentin in vesicular transport. And it’s not just parvovruses that need vimentin – herpesviruses do too (Hertel, L. (2011) Herpesviruses and intermediate filaments: close encounters with the third type. Viruses, 3(7), 1015-1040), and possibly dengue virus and HIV also.
Unfortunately, you’re not likely to be swallowing any drugs which disrupt your cytoskeleton because you are infected with a virus – that would be a really bad idea. But in terms of understanding how all the various components invoked in virus replication are moved to the correct location at the right time, the vimentin story is turning out to be very interesting.
The intermediate filament network protein, vimentin, is required for parvoviral infection. Virology. 06 Jul 2013 pii: S0042-6822(13)00358-9. doi: 10.1016/j.virol.2013.06.009
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.