@article{TEXTUAL,
      recid = {9572},
      author = {McCormick, Susan and He, Qi and Stern, Jordan and  Khodarev, Nikolai and Weichselbaum, Ralph and Skelly,  Christopher L.},
      title = {Evidence for the Use of Multiple Mechanisms by Herpes  Simplex Virus-1 R7020 to Inhibit Intimal Hyperplasia},
      journal = {PLOS ONE},
      address = {2015-07-01},
      number = {TEXTUAL},
      abstract = {Intimal hyperplasia (IH) is the primary cause of vein  bypass graft failure. The smooth muscle cell (SMC) is a key  element of IH as it phenotypically switches from a  contractile to a synthetic state which can become  pathological. R7020, which is an engineered strain of  Herpes Simplex Virus-1, inhibits IH in animal models.  Although it has many characteristics which make it a strong  candidate for use as a prophylactic agent how it inhibits  IH is not well understood. The objective of this study was  to identify modes of action used by R7020 to function in  blood vessels that may also contribute to its inhibition of  IH. The cytopathic effect of R7020 on SMCs was determined  in vitro and in a rabbit IH model. In vitro assays with  R7020 infected SMCs were used to quantify the effect of  dose on the release kinetics of the virus as well as the  effects of R7020 on cell viability and the adhesion of  peripheral blood mononuclear cells (PBMCs) to SMCs in the  absence and presence of tumor necrosis factor alpha  (TNF-α). The observed cytopathic effect, which included  R7020 positive filopodia that extend from cell to cell and  the formation of syncytia, suggests that R7020 remains cell  associated after egress and spreads cell to cell instead of  by diffusion through the extracellular fluid. This would  allow the virus to rapidly infect vascular cells while  evading the immune system. The directionality of the  filopodia in vivo suggests that the virus preferentially  travels from the media towards the intima targeting SMCs  that would lead to IH. The formation of syncytia would  inhibit SMC proliferation as incorporated cells are not  able to multiply. It was also observed that R7020 induced  the fusion of PBMCs with syncytia suggesting the virus may  limit the effect of macrophages on IH. Furthermore, R7020  inhibited the proliferative effect of TNF-α, an  inflammatory cytokine associated with increased IH. Thus,  the results of this study suggest that R7020 inhibits IH  through multiple mechanisms.},
      url = {http://knowledge.uchicago.edu/record/9572},
}