A study of the immunologic response to second heterotypic bluetongue virus infection in mice

Typescript (photocopy).The first phase of the study involved the development of 2 immunological techniques, (1) an avidin/biotin-enhanced enzyme-linked immunosorbent assay (A/B-ELISA) and (2) an avidin/biotin-enhanced immunoperoxidase staining procedure, for the detection and measurement of serological responses of mice to bluetongue virus (BTV) infection and the demonstration of BTV antigen in mouse tissues. Results indicated that the A/B-ELISA is an effective assay for serum antibody produced against BTV in the mouse; and that BTV antigen is detectable in infected mouse tissues with the avidin/biotin-enhanced immunoperoxidase technique. The 2 immunological techniques were utilized in the second phase of the study to investigate the immune response of adult mice to selected single and sequential BTV serotype infections, and to investigate the effect of prior passive immunization on the immune response of adult mice to subsequent BTV infection. Results indicated that the C57B1/6 strain of mice responded with low antibody titers following a single BTV infection, but that titers significantly increased following either sequential homotypic (same serotype) or heterotypic (different serotype) infections. It was further demonstrated that the immune response following heterotypic BTV infections was greater than that following homotypic infections. These observations along with immunoabsorbent studies suggest that much of the response to heterotypic infections is directed against the secondarily infecting virus serotype. These results are in contrast with previous views, based largely on in vitro serum neutralization tests, that infection of an animal by 1 serotype of a virus should not alter the host immune response to infection by a different serotype of that virus. Clinical signs of illness were not observed nor were histologic lesions recognized in any of the mice infected with BTV. Neither was specific immunoperoxidase staining observed in the tissues of adult experimental mice killed 14 days after the last virus infection. However, BTV antigen was readily demonstrable in positive control suckling mouse brain sections and in the hearts and spleens of adult control mice killed on days 5 and 6 following BTV infection