Replication of Aleutian mink disease parvovirus in vivo is influenced by residues in the VP2 protein

Aleutian mink disease parvovirus (ADV) is the etiological agent of Aleutian disease of mink Several ADV isolates have been identified which vary in th e severity of the disease they elicit. The isolate ADV-Utah replicates to h igh levels in mink, causing severe Aleutian disease that results in death w ithin 6 to 8 weeks, but does not replicate in Crandell feline kidney (CrFK) cells. In contrast, ADV-G replicates in CrFK cells but does not replicate in mink The ability of the virus to replicate in vivo is determined by vira lly encoded determinants contained within a defined region of the VP2 gene (M. E. Bloom, J. M. Fox, B. D. Berry, K. L. Oie, and J. B. Wolfin-barger. V irology 251:288-296, 1998). Within this region, ADV-G and ADV-Utah differ a t only five amino acid residues. To determine which of these five amino aci d residues comprise the in vivo replication determinant, site-directed muta genesis was performed to individually convert the amino acid residues of AD V-G to those of ADV-Utah. A virus in which the ADV-G VP2 residue at 534, hi stidine (H), was converted to an aspartic acid (D) of ADV-Utah replicated i n CrFK cells as efficiently as ADV-G. H534D also replicated in mink, causin g transient viremia at 30 days postinfection and a strong antibody response . Animals infected with this virus developed diffuse hepatocellular microve sicular steatosis, an abnormal accumulation of intracellular fat, but did n ot develop classical Aleutian disease. Thus, the substitution of an asparti c acid at residue 534 for a histidine allowed replication of ADV-G in mink, but the ability to replicate was not sufficient to cause classical Aleutia n disease.