The autonomous parvoviruses are single-stranded DNA viruses which are recognized primarily for their teratogenic effects in both natural and experimental infections. In vitro these viruses are dependent, for lytic replication, upon host cell factor(s) expressed transiently during the S phase, but are unable to stimulate resting cells to enter the mitotic cycle. This is believed to be the basis of their predilection for proliferating tissues as targets for attack in vivo. Some members of the group, such as Feline Panleukopenia Virus and Aleutian Disease Virus, cause disease in adult animals which is characterized by extensive lymphoid involvement. Parvovirus strains often show extreme specificity for target cells of a particular differentiated phenotype, for example, the immunosuppressive (i) strain of Minute Virus of Mice (MVM) replicates lytically in activated murine T-lymphocytes, which are resistant to prototype MVM. Parvoviruses have also been found occasionally to jump species barriers, and to segregate strains with new tissue tropisms. These properties have led to the suggestion that the severe T-lymphocyte depletion which underlies Acquired Immune Deficiency Syndrome (A1DS) may be the result of infection with a human T-cell-tropic parvovirus, acting in synergy with a state of lymphoproliferative stress. To test this hypothesis, a mouse analog of A1DS will be sought, using infection with MVM(i) in conjunction with T-cell activators such as mitogens, viruses or allogeneic cells, to produce a profound T-cell depletions. The proposed research will also test the implications and predictions derived from this model system for human A1DS. For this, reagent designed to detect viruses related to any of the known mammalian parvoviruses will be developed. A panel of genomic DNA clones will be constructed which will detect, at least at low stringency hybridization, the genomes of all known parvoviruses. Radioimmunoassays using bacterial plasmids which express the widely-conserved antigenic determinants carried on parvovirus non-structural polypeptides will also be developed. These tools will be tested for their ability to demonstrate parvovirus involvement in the mouse analog, and this information and these probes used to explore a potential parvoviral etiology for human A1DS. The mouse analog will also be used to develop methods for detecting novel parvoviruses unrelated, antigenically or by DNA:DNA hybridization, to currently known agents.
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