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 nonpathogenic for mink, whereas the highly pathogenic ADV-Utah isolate is nonviable in CRFK cells. To assign control of host range in CRFK cells and pathogenicity to specific regions of the ADV genome, we constructed a full-length molecular clone chimeric between ADV-G and ADV-Utah. If either the map unit (MU) 54-65 (clone G/U-5) or MU 65-88 (clone G/U-7) sections were ADV-Utah, viability in CRFK cells was abolished, thus indicating that in vitro host range was controlled by two independent determinants: A in the MU 54-65 segment and B in the MU 65-88 segment. Determinant 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 cells, an observation suggesting that expression of the B determinant required interaction between noncontiguous sequences. Adult mink of Aleutian genotype inoculated with G/U-8 or G/U-10 developed viremia, antiviral antibody, and histopathological changes characteristic of progressive Aleutian disease. The capsid sequences of G/U-8 and G/U-10 differed from ADV-G at five and four amino acid residues, respectively. Our results suggested that the host range and pathogenicity of ADV are regulated by sequences in the capsid protein gene.
Bloom
M E
ME
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, 59840, USA. mbloom@nih.gov
Fox
J M
JM
Berry
B D
BD
Oie
K L
KL
Wolfinbarger
J B
JB
D000454:Aleutian Mink Disease Virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D000818:Animals; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D036022:Capsid Proteins; D002415:Cats; D002460:Cell Line; D003001:Cloning, Molecular; D007668:Kidney / Q000821:virology; D008907:Mink; D010449:Peptide Mapping; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014779:Virus Replication
D036022:Capsid Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C442555:VP2 protein, Aleutian mink disease virus