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 nons tructural 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 (no npathogenic) and ADV-Utah (pathogenic), compared with G/U-10. Animals-32 eight-month-old female sapphire mink (Mustela vison). Procedure-Chimeric viruses were constructed, propagated in vitro, and used to inoculate mink. Antiviral antibody responses, presence of serum viral nu cleic acid, and serum gamma globulin concentrations were monitored for 120 days following inoculation. Histologic examination of the liver, kidneys, s pleen, 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 detec tion of viral nucleic acid in serum, gamma globulin response, and histologi c changes in mink inoculated with chimeras containing a valine residue at c odon 352 (352V) of VP2 capsid were increased, compared with values from min k inoculated with chimeric viruses that did not contain 352V. Conclusions and Clinical Relevance-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 determin ant of ADV. Further characterization of the pathogenic determinant may allo w future development of focused preventive and therapeutic interventions fo r Aleutian disease of mink.