STRUCTURE AND FUNCTION OF THE ALEUTIAN MINK DISEASE PARVOVIRUS GENOME

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The ongoing purpose of this project is to identify genomic differences among various strains of Aleutian mink disease parvovirus (ADV) and to relate these differences to viral host range and pathogenicity. Viruses from an ongoing outbreak of ADV infection in Utah were studied. PCR was used to isolate and characterize the 161 bp core hypervariable region of the capsid protein gene. Sequence of specimens from multiple mink and feral raccoons involved in the outbreak were very closely related to each other (>97%). Furthermore, they were more closely related to the type 1 nonpathogenic ADV-G (>97%) than to pathogenic strains such as the type 2 ADV-Utah, the type 3 Danish ADV-K or an isolate from feral skunks (all <90%). Expanded sequencing of a virus derived from this outbreak (ADV-TR) indicated that at other residues, the capsid protein gene differed from ADV-G and more closely resembled pathogenic strains of ADV. Thus, a virus with a type 1 hypervariable region can be pathogenic, however, these results indicate that viral determinants for pathogenicity and host range may be extremely complex. ADV-TR was highly pathogenic for both Aleutian and non-Aleutian genotype mink. Pathogenic strains of ADV, including ADV-TR, induced antiviral antibodies and viremia, but no evidence of pathology in raccoons. ADV-TR could be passaged from infected raccoons to mink. Thus, raccoons may play a role in maintenance and transmission of ADV. Other work designed to examine function of the transcription unit from the capsid protein P36 promoter has been undertaken. First strand cDNAs have been prepared from cells transfected with several parvovirus promoter constructs for use in 5'-RACE to compare the transcription initiation site under constitutive and trans-activated conditions. The 5'-RACE fragments have been cloned and are being characterized.