Vesicular Stomatitis Virus Modulates Invadopodia Development in SRC-Transformed Fibroblasts

Vesicular stomatitis virus (VSV) is well-appreciated for its oncotropism and immunostimulatory abilities, but its potential effects on the invasive properties of cancer cells has been little studied. Here, we test the effects of VSV on the formation of actin-dense, proteolytic cell surface protrusions called invadopodia in Src-transformed fibroblasts. Because VSV is known to alter the actin cytoskeleton, we hypothesized that VSV would significantly impact the formation and/or function of invadopodia in this cell line. The results of this study revealed that both a wild-type (rwt) and M protein mutant strain (rM51R-M) of VSV were capable of diminishing invadopodia-associated gelatin degradation activity by up to ~70%. This coincided with a reduction of punctate-shaped invadopodia but an increase in invadopodia rosettes. Similar effects were observed under both asynchronous and synchronous infection conditions. We speculate that VSV selectively infects cells producing invadopodia due to viral surfing. We also propose that VSV may sequester invadopodia machinery for productive infections resulting in defective invadopodia rosettes. Alternatively, remaining rosettes may represent circular dorsal ruffles, which are known to facilitate the uptake of virus into cells. This interference of invadopodia development may extend VSV's utility as an oncolytic virotherapy.<p></p>