Viral Replication And Platelet Adhesiveness To Vascular Endothelium

Abstract

Newcastle disease virus (NDV) and chikungunya virus (CV) replicated in monolayers of human umbilical vein endothelium to peak titres of 104.5 TCD50 per ml in 24 and 48 hours respectively following inoculation of 106 TCD50/ml of virus. The cultures demonstrated no cytopathic effects after 6 days incubation. Analysis of intracellular protein from virus-infected endothelial cells by polyacrylamide gel electrophoresis of 35s-methionine labelled extracts of infected and uninfected cells indicated that at 22 hours after infection, normal cellular protein synthesis was shut down and virus-specific protein was found inside the cells. In contrast, Influenza A viruses (HK and PR 8) did not replicate in endothelial cells. Endothelial cells exposed to a high dose of NDV were severely damaged as illustrated by rounding and stranding. Influenza A and CV did not exhibit this toxic effect. Although both NDV and CV demonstrated replication, they showed contrasting thrombo- genic effects in virus endothelium platelet reactions. Larger amounts of radioactivity were associated with endothelial cells when washed suspensions of 51Cr-labelled human platelets were added 24 hours after infection with NDV than when exposed to heat inactivated NDV or allantoic fluid. Platelets added to cultures infected with non-toxic doses of NDV or influenza virus adhered singly and in clumps to the surface of the endothelial cells, but not to those infected with CV. Identical results were attained when platelets, pre-incubated with virus, were placed on uninfected endothelial cell monolayers, then washed with buffer. The mechanism by which this adhesion takes place may be due to virus bridging or modification of endothelial cell membranes by viral neuraminidase leading to a depression of endothelial cell properties responsible for antiadhesiveness.