CONSTRUCTION OF PATHOGENIC MOLECULAR CLONES OF ALEUTIAN MINK DISEASE PARVOVIRUS THAT REPLICATE BOTH IN-VIVO AND IN-VITRO

The ADV-G isolate of Aleutian mink disease parvovirus (ADV) replicates permissively in Crandell feline kidney (CRFK) cells but is nonpathoge nic for mink, whereas the highly pathogenic ADV-Utah isolate is nonvia ble in CRFK cells. To assign control of host range in CRFK cells and p athogenicity to specific regions of the ADV genome, we constructed a f ull-length molecular clone chimeric between ADV-G and ADV-Utah. If eit her the map unit (MU) 54-65 (clone G/U-5) or MU 65-88 (clone G/U-7) se ctions were ADV-Utah, viability in CRFK cells was abolished, thus indi cating that in vitro host range was controlled by two independent dete rminants: A in the MU 54-65 segment and B in the MU 65-88 segment. Det erminant B could be divided into two subregions, B1 (MU 65-69) and B2 (MU 73-88), neither of which alone could inhibit replication in CRFK c ells, an observation suggesting that expression of the B determinant r equired interaction between noncontiguous sequences. Adult mink of Ale utian genotype inoculated with G/U-8 or G/U-10 developed viremia, anti viral antibody, and histopathological changes characteristic of progre ssive Aleutian disease. The capsid sequences of G/U-8 and G/U-10 diffe red from ADV-G at five and four amino acid residues, respectively. Our results suggested that the host range and pathogenicity of ADV are re gulated by sequences in the capsid protein gene.