Evidence for the isolation of a new virus from ulcerative colitis patients

Abstract

To assess the possible role of viral infection in the development of ulcerative colitis (UC) and of Crohn's disease (CD), electron-microscopic, physical, and chemical studies were performed on viral agents cultivated in tissue culture following inoculation with surgical specimens obtained from patients with CD, UC, and from control patients with other gastrointestinal diseases. Viral isolates obtained from CD patients were compared with those from UC patients. Each of the agents produced cytopathic change (CPE) in the tissue culture systems used, rabbit ileum (RI), Peking duck, and Riff free chick embryo, and had similar physical and chemical properties including ether resistance, temperature stability, and lack of inhibition by methotrexate. The three tissue culture systems supported viral growth and produced virus-like particles from CD filtrates with similar morphologic appearance, including a central core and an outer coat. Electron-microscopic studies revealed that the particle from CD has a diameter of 60 nm (range 42–71 nm). The agent isolated from UC patients also has a mean particle diameter of 60 nm (range 45–75 nm). The CD and UC agents produced different CPE in RI tissue culture. Agents different from CD-and UC-derived viruses were isolated from one patient with necrotizing enterocolitis and from three patients with carcinoma of the colon. Ileal homogenates of other control patients failed to reveal evidence of viral contaminants and evaluation of the tissue culture systems revealed no adventitious agents. Virus was found in diseased as well as in adjacent histologically normal CD tissue. Guinea pig antibody prepared against CD-derived agents inhibited the growth of each of the CD agents but not of the agents from UC, necrotizing enterocolitis, or colon carcinoma. Antibody directed against the agents from UC failed to inhibit growth of the agents from CD, necrotizing enterocolitis, or colon carcinoma. The current studies therefore suggest that a virus has now been cultivated from UC patients which produced CPE different from the viruses previously cultivated from CD patients and which lacks cross-reactivity with the CD derived virus. Since each filtrate produced viruses in the three different tissue culture systems, these viruses are not tissue culture contaminants but are derived from the human filtrates. These studies also suggest an association between viruses and inflammatory bowel disease but do not establish an etiologic relationship.