While most chemokine receptors fail to cross the chemokine class boundary with respect to the ligands that they bind, the human cytomegalovirus (HCMV)-encoded chemokine receptor US28 binds multiple CC-chemokines and the CX₃C-chemokine Fractalkine. US28 binding to CC-chemokines is both necessary and sufficient to induce vascular smooth muscle cell (SMC) migration in response to HCMV infection. However, the function of Fractalkine binding to US28 is unknown. In this report, we demonstrate that Fractalkine binding to US28 not only induces migration of macrophages but also acts to inhibit RANTES-mediated SMC migration. Similarly, RANTES inhibits Fractalkine-mediated US28 migration in macrophages. While US28 binding of both RANTES and Fractalkine activate FAK and ERK-1/2, RANTES signals through Gα12 and Fractalkine through Gαq. These findings represent the first example of differential chemotactic signaling via a multiple chemokine family binding receptor that results in migration of two different cell types. Additionally, the demonstration that US28-mediated chemotaxis is both ligand-specific and cell type–specific has important implications in the role of US28 in HCMV pathogenesis. Chemokines are small cytokines that are critical for recruiting and activating the cells of the immune system during viral infections. A number of viruses, including the large herpes virus human cytomegalovirus (HCMV), encode mechanisms to impede the effects of chemokines or have gained the ability to use these molecules to their own advantage. HCMV encodes multiple chemokine receptors including US28, which binds two different classes of chemokines namely the CC and CX₃C families. In this report, we demonstrate that US28 binding to a CC chemokine elicits different responses compared to when binding to Fractalkine, the only CX₃C chemokine. RANTES (CC chemokine) binding to US28 mediates smooth muscle cell migration, but Fractalkine blocks this process in a dose-dependent manner. However, Fractalkine binding to US28 can specifically mediate the migration of macrophages, another important cell type during viral pathogenesis. We explored the intracellular signaling pathways responsible for each migration event and determined that they differ in the G-proteins that are coupled to US28 following addition of ligand and that this occurs in a cell type–specific manner. These results provide a new mechanism for HCMV acceleration of vascular disease via the specific migration of macrophages and provide the first example of cell type–specific migration via multiple chemokines binding to a single receptor.

In 2012, swine influenza surveillance detected a novel reassorted influenza A virus (IAV) strain containing human-seasonal hemagglutinin (HA) and neuraminidase (NA). Subsequently, these viruses reassorted, maintaining only the human-origin H3, which resulted in a new lineage of viruses that became the most frequently detected H3 clade in US swine (2010.1 HA clade). Here, we assessed the antigenic phenotype, virulence, and transmission characteristics of this virus lineage following its introduction to swine. Relative to 2010.1 viruses from 2012 and 2014, recent 2010.1 contemporary strains from 2015 to 2017 resulted in equivalent macroscopic lung lesions and transmission in pigs. A single mutation at amino acid residue 145 within the previously defined HA antigenic motif was associated with a change of antigenic phenotype, potentially impairing vaccine efficacy. Contemporary 2010.1 viruses circulating in swine since 2012 were significantly different from both pre-2012H3N2 in swine and human-seasonal H3N2 viruses and demonstrated continued evolution within the lineage.

In 2012 scientists funded by the United States Defense Advanced Research Projects Agency (DARPA) produced 10 million doses of influenza vaccine in tobacco in a milestone deadline of one month. Recently the experimental antibody cocktail Zmapp™, also produced in tobacco, has shown promise as an emergency intervention therapeutic against Ebola virus. These two examples showcase how collaborative efforts between government, private industry and academia are applying plant biotechnology to combat pathogenic agents. Opportunities now exist repurposing tobacco expression systems for exciting new applications in synthetic biology, biofuels production and industrial enzyme production. As plant-produced biotherapeutics become more mainstream, government funding agencies need to be cognizant of the idea that many plant-produced biologicals are often safer, cheaper, and just as efficacious as traditionally used expression systems.

To better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems. We evaluated the kinetics of uptake, germination and proliferation of Bacillus anthracis Sterne spores in association with human primary lung epithelial cells, Calu-3 and A549 cell lines. We also analysed the influence of various cell culture medium formulations related to spore germination. We found negligible spore uptake by epithelial cells, but germination and proliferation of spores in the serum-free extracellular environment was evident. Spore germination was appreciably higher in immortalized cell cultures than in primary epithelial cells. Additionally, spores still germinated apically at a mucus-secreting air–liquid interface lung barrier that was devoid of cell culture medium much earlier than medium-only controls. The role of lung epithelial cells in B. anthracis spore dissemination after inhalation remains poorly defined and rather controversial. These results are novel as they show spore germination is appreciably enhanced in the presence of lung cells in vitro, however, the cell line and cell state (air–liquid interface vs submerged in medium) dictates the extent of germination and in some cases proliferation.