Effect of a valine residue at codon 352 of the VP2 capsid protein on in vivo replication and pathogenesis of Aleutian disease parvovirus in mink.
OBJECTIVE
To determine whether a group of 3 genetic differences in the nonstructural protein (NS1) or 1 genetic difference in the structural protein (VP2) of Aleutian disease parvovirus (ADV) is responsible for an increase in the in vivo replication and pathogenicity of G/U-8, a chimera of ADV-G (nonpathogenic) and ADV-Utah (pathogenic), compared with G/U-10.


METHODS
32 eight-month-old female sapphire mink (Mustela vison).


METHODS
Chimeric viruses were constructed, propagated in vitro, and used to inoculate mink. Antiviral antibody responses, presence of serum viral nucleic acid, and serum gamma globulin concentrations were monitored for 120 days following inoculation. Histologic examination of the liver, kidneys, spleen, and mesenteric lymph nodes was performed after necropsy.


RESULTS
A chimera containing only the 3 amino acid substitutions in NS1 did not elicit measurable responses indicative of replication or pathogenicity in inoculated mink. Serum antiviral antibody responses, frequency of detection of viral nucleic acid in serum, gamma globulin response, and histologic changes in mink inoculated with chimeras containing a valine residue at codon 352 (352V) of VP2 capsid were increased, compared with values from mink inoculated with chimeric viruses that did not contain 352V.


CONCLUSIONS
A valine residue at codon 352 in the VP2 capsid protein of ADV affects in vivo viral replication and pathogenicity. This amino acid may be part of an incompletely defined pathogenic determinant of ADV. Further characterization of the pathogenic determinant may allow future development of focused preventive and therapeutic interventions for Aleutian disease of mink.
Stevenson
M A
MA
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIH, NIAID, Hamilton, MT 59840, USA.
Fox
J M
JM
Wolfinbarger
J B
JB
Bloom
M E
ME
D000453:Aleutian Mink Disease / Q000097:blood / Q000473:pathology / Q000821:virology*; D000454:Aleutian Mink Disease Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000737:chemistry / Q000235:genetics*; D036022:Capsid Proteins; D002678:Chimera / Q000235:genetics; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D003378:Counterimmunoelectrophoresis / Q000662:veterinary; D004279:DNA, Viral / Q000097:blood; D006651:Histocytochemistry / Q000662:veterinary; D008907:Mink / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D018709:Statistics, Nonparametric; D005719:gamma-Globulins / Q000032:analysis
D000914:Antibodies, Viral; D036022:Capsid Proteins; D003062:Codon; D004279:DNA, Viral; C442555:VP2 protein, Aleutian mink disease virus; D005719:gamma-Globulins