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UnlabelledLipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles.ImportanceThe lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry.

Black patients have higher mortality and are less likely to receive liver transplantation for hepatocellular carcinoma (HCC) than white patients. Reasons for these disparities have not been fully elucidated. Comorbid disease, liver disease severity, cirrhosis etiologies, and tumor characteristics were compared between black and white patients with HCC seen at the Indiana University Academic Medical Center from January 2000 to June 2014. Logistic regression was used to investigate the primary outcome, which was liver transplantation. Log‐rank testing was used to compare survival between the two groups. Subgroup analysis explored reasons for failure to undergo liver transplantation in patients within Milan criteria. The cohort included 1,032 (86%) white and 164 (14%) black patients. Black and white patients had similar Model for End‐Stage Liver Disease (MELD) and Child‐Pugh scores (CPSs). There was a trend toward larger tumor size (5.3 cm versus 4.7 cm; P = 0.05) in black patients; however, Barcelona Clinic Liver Cancer (BCLC) staging and Milan criteria were similar. Black patients were less likely to undergo liver transplantation than white patients; this was a disparity that was not attenuated (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.21‐0.90) on multivariable analysis. Substance abuse was more frequently cited as the reason black patients within Milan criteria failed to undergo transplantation compared to white patients. Survival was similar between the two groups. Conclusion: Racial differences in patient and tumor characteristics were small and did not explain the disparity in liver transplantation. Higher rates of substance abuse in black patients within Milan criteria who failed to undergo transplantation suggest social factors contribute to this disparity in this cohort. [ABSTRACT FROM AUTHOR]