The B19 parvovirus causes at least three human diseases including a non-destructive polyarthralgia in adults and in presently the only recognized human pathogen of this virus group. The RA-l virus, first described in 1984 as a new parvovirus from an adult patient with chronic, destructive rheumatoid arthritis (RA), remains to be qualified as a virus indigenous to human that is responsible for RA or any other human disorder. The major goals of this proposal are to: (1) demonstrate the incidence and expression of Ra-1 type viruses in different human population groups, (2) establish the identity of the RA-1 virus at the molecular and cellular levels as a possible unique member of the Parvoviridae family, and (3) define the in vitro growth requirements of these parvoviruses. Blood sera from normal and diseased individuals of various age groups will be screened for RA-1 related antigens and antibody using sensitive tests such as enzyme-linked-immunosorbent-assays (ELISA) and Western protein blots. Synovial fluid and paired blood samples from patients with early synovitis or diagnosed RA will be included in this survey. Test for the presence of immune complexes that might ordinarily mask detection of either parvovirus antigens of antibodies in these specimens will be conducted. Cloned viral DNA probes will be used to detect RA-1 specific DNA or RNA in human blood and/or synovial samples. Ongoing DNA sequencing studies will be completed and computer programs will be used to identify the structural homologies of RA-1 and other parvoviruses. Synthetic polypeptides mimicking the putative viral structural proteins will be made and tested for their ability to elicit antibodies that confer protective immunity in animals and which may be useful diagnostic reagents. Efforts to develop a fully permissive system for propagation of the RA-1 virus will include use of human cells of the lymphoid/myeloid lineage exposed to modulators such as lymphokines, mitogens or prostaglandins. Cells containing stable inserts of potential helper virus genes will be tested for their permissiveness. This study should provide useful information about the possible health significance, identify and basic properties of the RA-1 parvovirus.
