Screening enteroviruses for beta-cell tropism using foetal porcine beta-cells

Primary adult human insulin-producing beta-cells are susceptible to infection by prototype strains of coxsackieviruses (CV) and infection may result in impaired beta-cell function and/or cell death, as shown for coxsackie B virus (CVB) types 4 and 5, or have no apparent immediate adverse effects, as shown for CVA-9. Because of the limited availability of human pancreatic beta-cells, the aim of this study was to find out if foetal porcine pancreatic islets could be used as a substitute in enterovirus (EV) screening. These cells resemble human beta-cells in several biological properties. CVB infection resulted in a rapid progressive decline of insulin content and reponsiveness to insulin release. The amount of virus inoculum sufficient for this destruction was small, corresponding to only 55 infectious units per pancreas. In contrast to CVBs, CVA-9 replicated poorly, and sometimes not at all, in foetal porcine beta-cells. The first signs of functional impairment and cell destruction, if present at all, were seen only after 1-3 weeks of incubation. Furthermore, CVA-16, several strains of echoviruses and human parechovirus type 1 were unable to replicate in foetal porcine pancreatic beta-cells. Based on these results, foetal porcine islets are somewhat more sensitive to CVB infection than adult human islets, whereas many other human EV strains do not infect porcine beta-cells. Therefore, foetal porcine beta-cells cannot be used for systematic screening of human EV strains and isolates for beta-cell tropism, but they might provide a useful model for detailed studies on the interaction of CVBs with beta-cells.