JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 2286754): 4-month-old female mink
HISTORY: Four mink with history of dyspnea and a mild serous nasal discharge were submitted from a mink farm that was experiencing losses in the current kit crop.
HISTOPATHOLOGIC DESCRIPTION: Lung: The section of lung is diffusely consolidated. Alveolar septa are expanded up to 10 times normal by macrophages, fewer lymphocytes and plasma cells, as well as interstitial edema and variable amounts of necrotic cellular debris. Alveoli are often lined by plump, cuboidal epithelium (type II pneumocyte hyperplasia) which rarely contain variably sized (up to 12um diameter), homogenous, indistinct, amphophilic intranuclear viral inclusion bodies. Alveolar lumina are variably filled with foamy alveolar macrophages, eosinophilic fibrillar material (fibrin), and sloughed necrotic debris. Diffusely, perivascular, peribronchiolar, and subpleural connective tissue is expanded by moderate numbers of plasma cells and lymphocytes with edema and dilated lymphatics. Bronchioles and bronchi contain variable amounts of fibrin with few macrophages, plasma cells and lymphocytes. The pleura is multifocally mildly thickened up to twice normal by fibrous connective tissue.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, necrotizing, histiocytic, diffuse, marked, with type II pneumocyte hyperplasia, peribronchial and perivascular lymphoplasmacytic infiltrates, and rare amphophilic viral intranuclear inclusion bodies, mink (Mustela vision), mustelid.
ETIOLOGIC DIAGNOSIS: Parvoviral pneumonia
CAUSE: Aleutian mink disease virus (ADV, AMDV)
- Single-stranded DNA virus; family Parvoviridae, genus Amdovirus, with several strains with variable virulence; typically a disease of farm-raised mink (a disease of financial importance worldwide)
- Disease signs vary with the age and coat color of mink, as well as strain of virus
- 4 viral strains recognized: Utah-1, Ontario, Montana, and Pullman
- Coat color: Mink homozygous for the Aleutian gene (blue coat color) are especially susceptible, heterozygous individuals are less severely affected, and mink lacking this gene are susceptible but may carry and excrete the virus for years without clinical signs
- The Aleutian gene is linked to a gene responsible for a lysosomal abnormality (Chediak-Higashi syndrome) of granulocytes, which inhibits destruction of phagocytized immune complexes
- Chediak-Higashi syndrome is presumed to be a defect in the lysosomal trafficking gene (LYST) that results in defective melanosomes, lysosomes, platelet-dense granules, and cytolytic granules in many cell types, including melanocytes, neutrophils, monocytes, natural killer lymphocytes, and platelets
- In general, all parvoviruses are dependent on the S-phase of the host cell cycle for virus replication, and therefore induce greatest cytolytic disease in tissues with a high mitotic rate, including lymphoid tissues undergoing antigenic stimulation; virus localization is limited to certain cell types that bear the appropriate viral receptors
- Virus is shed in saliva, urine, and feces; transmission is via inhalation or ingestion; vertical transmission is mainly responsible for maintaining the virus in a population in the wild (solitary animals)
- Virus replicates and becomes sequestered in macrophages and dendritic cells; abundant viral antigen usually found in Kupffer cells and lymphoid organs
- In adults, strong humoral immune response is elicited à increased gamma globulins; with persistent infection, persistent antigenic stimulation à antigen-antibody complex deposition (type III hypersensitivity)à clinical signs (e.g. immune-complex glomerulonephritis and arteritis); in older mink, death is attributed to glomerulonephritis or secondary infection following immunosuppression
- In young animals (kits), virus has cytocidal effect on pneumocytes and disease manifests as an acute interstitial pneumonia
TYPICAL CLINICAL FINDINGS:
- Kits: Acute pneumonia à lethargy, increasingly labored breathing, unconsciousness, death
- Adults: hypergammaglobulinemia (usually >20% of total serum protein), plasmacytosis, lethargy, anorexia, cachexia, polydipsia, fever, blood exuding from the mouth and anus; in persistently infected mink, infertility and abortion
TYPICAL GROSS FINDINGS:
- Kits: Noncollapsing, patchy to diffusely red lungs; hepatomegaly, splenomegaly
- Adults: Splenomegaly and/or splenic congestion, lymphadenopathy, hepatomegaly and/or hepatic chronic passive congestion, renomegaly; gingivitis, oral ulcers, multiple hemorrhages, arteritis, enlarged pale yellow kidneys with petechiae, pitting, or atrophy
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Large basophilic to amphophilic intranuclear inclusion bodies are common
- Kits: Acute interstitial pneumonia with type II pneumocyte hyperplasia, hyaline membrane formation, and amphophilic intranuclear inclusion bodies
- Adults: Immune-complex glomerulonephritis and arteritis; plasma cell infiltrates in the renal interstitium, hepatic portal areas, and red pulp of the spleen; bile duct proliferation; multifocal lymphocytic infiltrates are common and tentatively diagnostic
- Parvovirus: Icosahedral intranuclear viral particles 26-28nm in diameter; chromatin usually clumped at the nuclear membrane
ADDITIONAL DIAGNOSTIC TESTS:
- PCR, in-situ hybridization, counter-immunoelectrophoresis (CEP), IFA, radioimmunoassay, complement fixation, ELISA
- Canine distemper virus: Eosinophilic intracytoplasmic inclusions
- Orthomyxovirus (influenza): Inclusions are rare
- Mink enteritis virus: Viral isolation may be necessary to differentiate
ADV in other species:
- First discovered in mink, later in domestic ferrets and wild mustelids (striped skunk)
- Ferret-derived strains are different from mink-derived strains; although the mink strains of ADV can infect ferrets, there are several strains that are more commonly found in ferrets that are of lower virulence in mink
- Disease is similar but more insidious (chronic, progressive) than in mink
- Other reported disease presentations include: liver failure, intestinal disease including melena, and central nervous system disease
- Striped skunks (Vet Pathol. 2015)
- Multisystemic lymphoplasmacytic inflammation (interstitial nephritis, myocarditis, hepatitis, meningoencephalitis, pneumonia, splenitis)
- Immune complex deposition: Glomerulonephritis, multiorgan arteritis +/- fibrinoid necrosis
- Neurologic disease: encephalomalacia with cerebral microangiopathy
Parvovirus in many species targets crypt epithelium of the small intestine, resulting in intestinal disease. Rodent parvoviruses do not target intestinal epithelium.
- Porcine parvovirus: Stillbirth, abortion, fetal death, mummification, and infertility
- Feline panleukopenia virus (feline distemper): Affects all felids, mink, raccoons, and some other procyonids; generalized disease in kittens, with panleukopenia, enteritis; cerebellar hypoplasia
- Canine parvovirus 1: Minimal disease
- Canine parvovirus 2: Generalized neonatal disease; enteritis, nonsuppurative myocarditis (rare, 2-8 weeks old pups), lymphopenia
- Bovine parvovirus (BPV 1-3): unclear status as pathogen, possible cause of neonatal diarrhea and adult respiratory/reproductive disease
- Aleutian disease virus
- Mink enteritis virus: Panleukopenia, severe hemorrhagic enteritis
- Rat: subclinical infections common
- Toolan H-1 virus, Rat Minute Virus, Rat Parvovirus
- Rat Virus/Kilham’s Rat Virus (RV): The most pathogenic, may be the only to cause natural disease; causes lymph node congestion, body fat loss, scrotal hemorrhage, +/- splenomegaly, icterus, ascites, CNS hemorrhagic foci, focal hepatocellular necrosis and intranuclear inclusion bodies, cerebellar hypoplasia; upon recovery, liver may have focal angiectasis (peliosis hepatis) and nodular hyperplasia
- Minute virus of mice (MVM): Lymphocyte and endothelial tropism; dwarfism, cerebellar hypoplasia; disease is limited in duration with recovery in immunocompetent mice
- Mouse Parvovirus (MPV): Lymphocyte tropism; predominant parvoviral infection of mice (compared to MVM); infection is typically persistent
- Hamster parvovirus (possibly mouse parvovirus-3): Report of epizootic outbreak in suckling and weanling hamsters resulting in marked discoloration, malformation, and absence of incisor teeth, periodontitis, suppuration with mineralization and hemorrhage in the dental pulp, as well as domed calvaria and potbellied appearance
- Rabbit (Lapine parvovirus): typically clinically normal
- Goose parvovirus: Hepatitis, myocarditis, myositis
- Duck parvovirus: Hepatitis, myocarditis, myositis
- Chicken and turkey parvovirus: Enteritis
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016: 17-19, 122-124, 175-176, 196, 259
- Farid AH, Hussain I, Arju I. Detection of Aleutian mink disease virus DNA and antiviral antibodies in American mink (Neovison vison) 10 days postinoculation. Vet. Diagn. Invest. 2015:27(3):287-294.
- Kollias GV, Fernandez-Moran J. In: Miller RE, Fowler ME. Fowler’s zoo and wild animal medicine. Vol. 8. St. Louis, MO: Elsevier; 2015: 484.
- Kiupel M, Perpinan D. Viral diseases of ferrets. In: Fox JG, Marini RP. Biology and diseases of the ferret. 3rd ed. Ames, IA: Wiley; 2014: 461-467.
- LaDouceur EE, Anderson M, Ritchie BW, Ciembor P, Rimoldi G, Piazza M, Pesti D, Clifford DL, Gianniti F. Aleutian disease: an emerging disease in free-ranging striped skunks (Mephitis mephitis) from California. Pathol. 2015;52(6):1250-1253.
- Li L, Pesavento PA, Woods L, et al. Novel amdovirus in gray foxes. Emerg Infect Dis. 2011:17(10):1876-8.
- MacLachlan NJ, Dubovi EJ, Eds. Fenner’s Veterinary Virology. 5th ed. San Diego, CA: Academic Press. 2017;245-257.
- Nituch LA, Bowman J, Wilson PJ, Schulte-Hostedde AI. Aleutian mink disease virus in striped skunks (Mephitis mephitis): evidence for cross-species spillover. Wildl. Dis.2015;51(2):389-400.
- Quesenberry KE, Carpenter JW. Ferrets, Rabbits, and Rodents Clinical Medicine and Surgery. 3rd ed. St. Louis, MO: Elsevier; 2012: 48, 71-73, 135-136.
- Snyder PW. Diseases of immunity. In: Zachary JD, ed., Pathologic Basis of Veterinary Disease.6th ed. St. Louis, MO: Elsevier; 2017: 266.
- Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:153-158.
- Wilson DJ, Baldwin TJ, Whitehouse CH, Hullinger G. Causes of mortality in farmed mink in the intermountain west, North America. Vet. Diagn. Invest. 2015:27(4):470-475.