@article{pollara_spesock_pickup_laster_petty_2012, title={Production of prostaglandin E-2 in response to infection with modified vaccinia Ankara virus}, volume={428}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2012.03.019}, abstractNote={Prostaglandin E₂ (PGE₂) is an arachidonic acid (AA)-derived signaling molecule that can influence host immune responses to infection or vaccination. In this study, we investigated PGE₂ production in vitro by cells infected with the poxvirus vaccine strain, modified vaccinia Ankara virus (MVA). Human THP-1 cells, murine bone marrow-derived dendritic cells, and murine C3HA fibroblasts all accumulated PGE₂ to high levels in culture supernatants upon infection with MVA. We also demonstrated that MVA induced the release of AA from infected cells, and this was, most unusually, independent of host cytosolic phospholipase A₂ activity. The accumulation of AA and PGE₂ was dependent on viral gene expression, but independent of canonical NF-κB signaling via p65/RelA. The production of PGE₂ required host cyclooxygenase-2 (COX-2) activity, and COX-2 protein accumulated during MVA infection. The results of this study provide insight into a novel aspect of MVA biology that may affect the efficacy of MVA-based vaccines.}, number={2}, journal={VIROLOGY}, author={Pollara, Justin J. and Spesock, April H. and Pickup, David J. and Laster, Scott M. and Petty, Ian T. D.}, year={2012}, month={Jul}, pages={146–155} } @article{pollara_laster_petty_2010, title={Inhibition of poxvirus growth by Terameprocol, a methylated derivative of nordihydroguaiaretic acid}, volume={88}, ISSN={["0166-3542"]}, DOI={10.1016/j.antiviral.2010.09.017}, abstractNote={Terameprocol (TMP) is a methylated derivative of nordihydroguaiaretic acid, a phenolic antioxidant originally derived from creosote bush extracts. TMP has previously been shown to have antiviral and anti-inflammatory activities, and has been proven safe in phase I clinical trials conducted to evaluate TMP as both a topical and parenteral therapeutic. In the current study, we examined the ability of TMP to inhibit poxvirus growth in vitro, and found that TMP potently inhibited the growth of both cowpox virus and vaccinia virus in a variety of cell lines. TMP treatment was highly effective at reducing infectious virus yield in multi-step virus growth assays, but it did not substantially inhibit the synthesis of infectious progeny viruses in individual infected cells. These contrasting results showed that TMP inhibits poxvirus growth in vitro by preventing the efficient spread of virus particles from cell to cell. The canonical mechanism of poxvirus cell-to-cell spread requires morphogenesis of cell-associated, enveloped virions. The virions then trigger the formation of actin tails to project them from the cell surface. The number of actin tails present at the surface of poxvirus-infected cells was reduced dramatically by treatment with TMP. Whether TMP inhibits poxvirus morphogenesis, or subsequent events required for actin tail formation, remains to be determined. The results of this study, together with the clinical safety record of TMP, support further evaluation of TMP as a poxvirus therapeutic.}, number={3}, journal={ANTIVIRAL RESEARCH}, author={Pollara, Justin J. and Laster, Scott M. and Petty, Ian T. D.}, year={2010}, month={Dec}, pages={287–295} } @article{lynch_ray_oie_pollara_petty_sadler_williams_pickup_2009, title={Modified vaccinia virus Ankara can activate NF-kappa B transcription factors through a double-stranded RNA-activated protein kinase (PKR)-dependent pathway during the early phase of virus replication}, volume={391}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2009.06.012}, abstractNote={Modified vaccinia virus Ankara (MVA), which is a promising replication-defective vaccine vector, is unusual among the orthopoxviruses in activating NF-κB transcription factors in cells of several types. In human embryonic kidney (HEK 293T) cells, the MVA-induced depletion of IκBα required to activate NF-κB is inhibited by UV-inactivation of the virus, and begins before viral DNA replication. In HEK 293T, CHO, or RK13 cells, expression of the cowpox virus CP77 early gene, or the vaccinia virus K1L early gene suppresses MVA-induced IκBα depletion. In mouse embryonic fibroblasts (MEFs), MVA induction of IκBα depletion is dependent on the expression of mouse or human double-stranded RNA-activated protein kinase (PKR). These results demonstrate that events during the early phase of MVA replication can induce PKR-mediated processes contributing both to the activation of NF-κB signaling, and to processes that may restrict viral replication. This property may contribute to the efficacy of this vaccine virus.}, number={2}, journal={VIROLOGY}, author={Lynch, Heather E. and Ray, Caroline A. and Oie, Katrina L. and Pollara, Justin J. and Petty, Ian T. D. and Sadler, Anthony J. and Williams, Bryan R. G. and Pickup, David J.}, year={2009}, month={Sep}, pages={177–186} }