Pathogenesis of Aleutian Mink Disease Parvovirus and Similarities to B19 Infection

Abstract

Aleutian mink disease parvovirus (ADV) is an unusual member of the autonomous parvoviruses in both its replication and pathogenesis. Infection of newborn mink kits results in an acute disease typified by virus replication in type II pneumocytes in the lung. This replication is permissive and cytopathic, characterized by the production of high levels of viral replicative intermediates and infectious progeny. However, infection of adult Aleutian mink leads to a chronic form of the disease termed Aleutian disease (AD). In this case, virus replication occurs predominantly in lymph node macrophages and is restricted, with viral DNA replication, RNA transcription, protein expression and production of infectious progeny occurring at low levels. B19 is the only autonomous parvovirus known to infect humans. The primary site of virus replication in both children and adults is in erythrocyte precursors in the blood and bone marrow, although viral genomes have been detected in various other tissues. B19 infection often causes a self-limiting disease although persistent infection of B19 can occur in both immuno-compromised and -competent people. Perhaps the most striking similarity between infection with ADV or with B19 is the important role the humoral immune response to infection has in pathogenesis. It can be both protective and pathogenic. Due to of the central role of antibody in the disease caused by either virus, understanding the specific roles of antibody production in protection, antibody-mediated enhancement of infection, the establishment of persistent infection and immune-mediated pathology will provide insight into the pathogenesis of these infections. A second similarity between the two viruses is the ability to establish persistent infection. Persistence of ADV is associated with restricted replication. Although many cellular factors may contribute to restricted virus replication, the interactions between the major non-structural protein, NS1, and the cells are likely to be critical. Parallels exist between the expression and post-translational modification of ADV and B19 NS1 proteins that may contribute to restriction of virus replication. Thus, a study of the regulation of NS1 expression and its interactions with cell signalling pathways may lead to increased understanding of the restricted replication of these two viruses, and perhaps of persistent infection.

Effect of Persistent Infection of Mink with Aleutian Mink Disease Virus on Reproductive Failure

“…Tissue tropism is an important attribute affecting pathogenicity of the virus variants and is governed by minor changes in the amino acid sequence. After entering the body of adult mink, the virus continues replication in B and T lymphocytes as well as macrophages of the spleen and lymph nodes (4). Constant replication stimulates the humoral immune response leading to excessive synthesis of specific antibodies and generalised plasmacytosis and gammopathy.…”

“…On farms where the disease is endemic, persistent infection of mink with Aleutian mink disease virus (AMDV) has a significant impact on breeding and reproductive indices. AMDV exhibits a tropism especially to lymphoid tissue (4). Tissue tropism is an important attribute affecting pathogenicity of the virus variants and is governed by minor changes in the amino acid sequence.…”

Important mammalian veterinary viral immunodiseases and their control

“…Infection of newborn mink kits results in acute disease characterised by virus replication in type II pneumocytes in the lung. The replication is permissive and cytopathic, leading to fulminant interstitial pneumonia and fatal respiratory distress [114]. In adult mink, following primary infection progeny virus is disseminated by macrophages to liver, spleen, bone marrow and other lymphoid organs [115].…”

Internal polyadenylation of parvoviral precursor mRNA limits progeny virus production

“…Aleutian mink disease is an immune complex-mediated disease associated with persistent infection in adult mink (Best and Bloom, 2005b; Bloom et al, 1975; Eklund et al, 1968). Control of capsid protein production has been shown to govern the persistence of AMDV in infected host animals (Alexandersen et al, 1988; Christensen et al, 1993; Storgaard et al, 1993; Storgaard et al, 1997), which likely requires controlled low levels of capsid proteins.…”