Jm. Fox et al., Replication of Aleutian mink disease parvovirus in vivo is influenced by residues in the VP2 protein, J VIROLOGY, 73(10), 1999, pp. 8713-8719
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.