Human polyomaviruses BKV and JCV remain persistent in the infected individual following primary infection in childhood. The pathogenic potential of these viruses is expressed most clearly in immunocompromised populations. The objectives of the project are to evaluate, by prospective studies, the importance of these viruses in diseases occurring in the following populations: (i) patients with acquired immunodeficiency syndrome (AIDS); (ii) bone marrow transplant (BMT) recipients; (iii) individuals with primary immunodeficiency diseases; and (iv) immunologically normal or abnormal individuals with urinary tract disease. The following techniques will be used: ELISA for detection of BKV and JCV antigens in urine; dot blot hybridization assays for recognition of BKV and JCV nucleotide sequences in urinary cells and in tissues; ELISA for quantitation of BKV and JCV especific IgG and IgM in serum specimens; immunoperoxidase tests for identification of viral antigens in tissues; and virus-specific lymphoproliferative assays. Collaborative arrangements have been made so that each of the proposed projects will form a part of the on-going studies of these patients by other qualified investigators. The prospective studies are aimed at determining the following: (i) time of onset, duration and titers of viruria; (ii) if the infections are primary or a result of reactivation; (iii) if the serologic response to infection is impaired in the immunodeficient populations; (iv) if either primary or reactivation infection can be temporally related to any illness and if virus-specific antigen or pathology can be found in the suspect tissue; and (v) if the presence (and numbers) of lymphocytes capable of responding to BKV in the BMT donor affects the caracteristics of BKV excretion in the BMT recipient. In summary, the investigations will utilize senstive, accurate and simple methods, which have become available recently, to carefully examine pathogenicity and reactivation of human polyomavirus infections.
