Unique susceptibility of a human lung carcinoid tumor cell line to infection with BK virus

Abstract

Carcinoid syndrome is caused by the unregulated secretion of bioactive amines from neuroendocrine tumors arising primarily in the gastrointestinal tract and lungs. The incidence of carcinoid syndrome is 1–2/100,000 and the syndrome is thought to be increasing. Carcinoid tumors are relatively slow growing but can become highly metastatic. Currently, there is no effective therapy to inhibit cell proliferation or metastasis of neuroendocrine tumor (NET) disease. Polyomaviruses are a family of viruses that are able to transform cells and promote tumor formation. In this study, the polyomaviruses SV40, JCV, and BKV were used to assess the ability of polyomaviruses to productively infect a range of human carcinoid cell lines. Infection was assessed by the immunofluorescence detection of T antigen and V antigen. Viruses and cell lines that exhibited productive infections were subsequently assayed by FACS analysis for cell binding and dual promoter luciferase assay for early and late promoter activity. Most carcinoid cell lines were not susceptible to infection by polyomaviruses. However, BKV efficiently infected the pulmonary carcinoid H727 cell line but did not infect a control, non-carcinoid lung cell line (A549). BKV was found to bind to both the susceptible H727 cells and to the non-susceptible A549 cells but viral genes were only efficiently expressed in the H727 cell line. The data demonstrate that BKV can infect human pulmonary carcinoid cells. Infection does not seem to be solely mediated by the virus’ ability to bind to cells, as the virus will also bind to non-carcinoid control cells. Both early and late gene expression are supported by the pulmonary carcinoid cells.