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Pathogenesis of Aleutian mink disease parvovirus infection: effects of suppression of antibody response on viral mRNA levels and on development of acute disease
journal contribution
posted on 1994-02-01, 00:00 authored by Soren AlexandersenSoren Alexandersen, T Storgaard, N Kamstrup, B Aasted, D D PorterWe suppressed the B-cell development and antibody response in mink by using treatment with polyclonal anti-immunoglobulin M (anti-IgM) to study the effects of antiviral antibodies on development of Aleutian mink disease parvovirus (ADV)-induced disease in more detail. Newborn mink kits were injected intraperitoneally with 1 mg of either anti-IgM or a control preparation three times a week for 30 to 34 days. At 21 days after birth, groups of mink kits were infected with the highly virulent United isolate of ADV. At selected time points, i.e., postinfection days 9, 13, 29, and 200, randomly chosen mink kits were sacrificed, and blood and tissues were collected for analyses. The efficacy of immunosuppressive treatment was monitored by electrophoretic techniques and flow cytometry. Effects of treatment on viral replication, on viral mRNA levels, and on development of acute or chronic disease were determined by histopathological, immunoelectrophoretic, and molecular hybridization techniques. Several interesting findings emerged from these studies. First, antiviral antibodies decreased ADV mRNA levels more than DNA replication. Second, suppression of B-cell development and antibody response in mink kits infected at 21 days of age resulted in production of viral inclusion bodies in alveolar type II cells. Some of these kits showed mild clinical signs of respiratory disease, and one kit died of respiratory distress; however, clinical signs were seen only after release of immunosuppression, suggesting that the production of antiviral antibodies, in combination with the massive amounts of free viral antigen present, somehow is involved in the induction of respiratory distress. It is suggested that the antiviral antibody response observed in mink older than approximately 14 days primarily, by a yet unknown mechanism, decreases ADV mRNA levels which, if severe enough, results in restricted levels of DNA replication and virion production. Furthermore, such a restricted ADV infection at low levels paves the way for a persistent infection leading to immunologically mediated disease. The potential mechanisms of antibody-mediated restriction of viral mRNA levels and mechanisms of disease induction are discussed.
History
Journal
Journal of VirologyVolume
68Issue
2Pagination
738 - 749Publisher
American Society for MicrobiologyLocation
Washington, D.C.ISSN
0022-538XLanguage
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
1994, American Society for MicrobiologyUsage metrics
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Acute DiseaseAleutian Mink DiseaseAleutian Mink Disease VirusAnimalsAntibodies, Anti-IdiotypicAntibodies, ViralB-LymphocytesBlotting, NorthernBlotting, SouthernDNA ReplicationFemaleFlow CytometryImmunoglobulin MImmunosuppressionIn Situ HybridizationInclusion Bodies, ViralMaleMinkRNA ProbesRNA, MessengerRNA, ViralRespiratory Tract InfectionsTime FactorsScience & TechnologyLife Sciences & BiomedicineVirologyFELINE PANLEUKOPENIA VIRUSACUTE INTERSTITIAL PNEUMONIATUMOR NECROSIS FACTORENTERITIS VIRUSCANINE PARVOVIRUSGENE-EXPRESSIONMONOCLONAL-ANTIBODIESANTIVIRAL ANTIBODIESIFN-ALPHAREPLICATION
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