Search

The difficulty of glioblastoma treatment makes it a good candidate for novel therapies, such as oncolytic viruses. Vesicular stomatitis virus expressing Lassa virus glycoprotein (Lassa-VSV) showed significant promise in animal models using established glioblastoma cell lines. These experiments were to determine the susceptibility of low-passage, patient-derived cell lines to Lassa-VSV oncolysis. Four patient-derived glioblastoma cell lines were infected with Lassa-VSV that expresses green fluorescent protein (GFP) and analyzed by fluorescence microscopy, flow cytometry, and cell viability assays. Cells were also analyzed as tumorspheres containing primarily glioma stem-like cells. Three low-passage, patient-derived cells were further analyzed with RNA sequencing (RNA-seq). Individual cell lines varied somewhat in their levels of viral gene expression and time course of Lassa-VSV-induced cell death, but each was susceptible to Lassa-VSV. Brain Tumor Center of Excellence (BTCOE) 4765 cells had the highest level of expression of interferon-stimulated genes but were most susceptible to Lassa-VSV-induced cell death, indicating that more susceptible cells do not necessarily have lower interferon pathway activation. Cells cultured as tumorspheres and infected with Lassa-VSV also showed variable susceptibility to Lassa-VSV, but BTCOE 4765 cells were least susceptible. Thus, patient-derived brain tumor cells show variable responses to Lassa-VSV infection, but each of the lines was susceptible to VSV oncolysis., Graphical abstract, Vesicular stomatitis virus containing the glycoprotein of Lassa virus (Lassa-VSV) has oncolytic activity against well-established human glioblastoma (GBM) cell lines. The experiments here demonstrated the susceptibility to Lassa-VSV of patient-derived GBM cell lines that vary in their expression of GBM subtype-specific genes and also in glioma stem-like cells.

Zika virus (ZIKV) can generate a number of neurological dysfunctions in infected humans. Here, we tested the potential of human immune cells to protect against ZIKV infection in genetically humanized MISTRG mice. FACS analysis showed robust reconstitution of the mouse spleen with human T cells. Peripheral ZIKV inoculation resulted in infection within the brains of MISTRG mice. Mice that were reconstituted with human peripheral blood mononuclear cells (PBMC) showed a more rapid lethal response to ZIKV than the control mice lacking these immune cells. Immunocytochemical analysis of T cell markers CD3, CD45, or CD8 showed strong T cell presence in the brain, together with robust infection by ZIKV particularly in the excitatory pyramidal and granule neurons of the hippocampus. Infection was also found in cortex, striatum, the dopamine neurons of the substantia nigra, and other brain loci. Infection was considerably less in other regions such as the septum and hypothalamus. These data support the perspective that, rather than exerting a protective function, T cells may underlie some ZIKV-mediated neuropathology in the brain.

SummaryA low-complexity chemical flooding formulation has been developed for application in offshore environments. The formulation uses seawater with no additional water treatment beyond that which is normally performed for waterflooding (filtration, deoxygenation, etc.). The formulation is a mixture of an alkyl propoxy sulfate (APS) and an alkyl ethoxy sulfate (AES) with no cosolvent. With seawater only (no salinity gradient), the blend of APS and AES gives substantially higher oil recovery than a blend of APS and internal olefin sulfonate (IOS) in outcrop sandstone. This formulation also reduces complexity, increases robustness, and potentially improves project economics for onshore projects as well.It is shown that the highest oil recovery is obtained with surfactant blends that produce formulations that are underoptimum (Winsor Type I phase behavior) with reservoir crude oil. Also, these underoptimum formulations avoid the high-injection pressures that are seen with optimum formulations in low-permeability outcrop rock. The formulation recovers a similar amount of oil in reservoir rock in the swept zone. Overall recovery in reservoir rock is lower than outcrop sandstone due to greater heterogeneity, which causes bypassing of crude oil.A successful formulation was developed by first screening surfactants for phase behavior then fine tuning the formulation based on insights developed with corefloods in consistent outcrop rocks. The consistency of the outcrop is essential to understand cause and effect. Then, final floods were performed in reservoir rock to confirm that low interfacial tension (IFT) is propagated through the core.