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

Primary adult human insulin-producing beta -cells are susceptible to infect ion 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 pancr eatic islets could be used as a substitute in enterovirus (EV) screening, T hese cells resemble human beta -cells in several biological properties, CVB infection resulted in a rapid progressive decline of insulin content and r eponsiveness to insulin release. The amount of virus inoculum sufficient fo r 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 impair ment and cell destruction, if present at all, were seen only after 1-3 week s of incubation, Furthermore, CVA-16, several strains of echoviruses and hu man parechovirus type 1 were unable to replicate in foetal porcine pancreat ic 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 porc ine 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.