Signalment:  

4-year-old male rhesus macaque (Macaca mulatta).An adult male rhesus macaque was transferred from CRO to YNPRC and assigned to a renal transplantation study protocol. Post-transplant day 38, the monkey showed signs of failure to thrive after immunosuppression was induced by T-cell depletion and steroids, and maintained on anti rejection drugs. Animal continued to lose weight despite treatment with low dose steroids and antibiotics. Anemia was diagnosed and treatment with iron and B12, and a transfusion of irradiated whole blood (100mL) were given. Anorexia and weight loss continued. Due to poor prognosis the monkey was euthanized.

Gross Description:  

This adult male rhesus macaque weighed 5.20 kilograms. The animal was in a very thin body condition with prominent bony structures. Omental adhesions to the transplanted kidney were present. There were no other gross findings.

Histopathologic Description:

Microscopic examination of femoral bone marrow revealed hypercellular marrow with abnormal erythroid cells with bizarre nuclear forms and intranuclear inclusions. These cells have a glassy intranuclear eosinophilic inclusion body, stained pink or lilac, that displaces the chromatin to the periphery.

Ultrastructural examination revealed intranuclear viral particles and an occasional viral array characteristic of parvoviruses.

Morphologic Diagnosis:  

Hypercellularity of femoral bone marrow with numerous intra-nuclear viral inclusion of Simian Parvovirus.

Lab Results:  

Hematology Parameters	Pre-study	Post renal transplant Day 28	Post whole blood transfusion Prior to necropsy
RBC - μl	5.31	2.31	2.93
Hemoglobin - gm%	12.8	5.1	6.9
Hematocrit (HCT) - %	37.6	14.9	19.0
Reticulocyte count (RETIC) - % RBC	0.0	0.3	2.7
Mean corpuscular volume (MCV) - fl	70.8	64.5	64.8
Mean corpuscular hemoglobin (MCH) - pg	24.1	22.1	23.5
Mean corpuscular hemoglobin concentration (MCHC) - g/dL	34.0	34.2	36.3
Platelets	377000	373000	619000
WBC	8700	2860	1420
Neutrophils	2436 (28%)	1801 (63%)	908 (64%)
Lymphocytes	6003 (69%)	858 (30%)	454 (32%)
Monocytes	87 (1%)	143 (5%)	56 (4%)
Eosinophils	174 ( 2%)	57 (2%)	0 (0%)

Condition:  

Simian parvovirus

Contributor Comment:  

Simian parvovirus (SPV) is a erythrovirus within the Parvoviridae family, related antigenically to human B19 virus.1,2,4 All of the primate erythroviruses have a predilection for erythroid precursors. The epizoology of SPV is poorly understood, but infection has been recognized in cynomolgus and rhesus macaques.

In humans, B19 can persist at low levels in the bone marrow of infected humans for extended periods, establishing latency, and a similar situation can be anticipated to occur in macaques with the related SPV. Both viruses target rapidly dividing cells and demonstrate a tropism for cells within the erythrocytic lineage. In immunologically normal animals, infection has not been associated with clinical disease, but with immunosuppression or immunodeficiency; infection may cause anemia and widespread infection of erythroid cells. In bone marrow, poorly-defined eosinophilic intranuclear inclusions may be observed, in association with dyserythropoiesis.(4) Ultrastructural examination and in situ hybridization can be used to confirm the diagnosis.(4) Such infections and pathology have been observed in both SIV- and SRV-infected rhesus macaques, as well as in immunosuppressed cynomolgus macaques, in which severe clinical anemia has been diagnosed.(1,4)

A SPV infection can be particularly problematic in transplantation studies in which NHPs received some form of immunosuppressive therapy to prevent transplant rejection. Using a combination of molecular detection techniques such as PCR and serologic testing, monkeys can be screened prior to initiation of studies and the selection of viral-negative animals will help prevent transmission from donor to recipient. However, immunosuppression allows latent infection to manifest itself, as in this case.

JPC Diagnosis:  

1. Bone marrow: Erythrocytic hyperplasia, mild to moderate.
2. Bone marrow, erythrocytic precursors: Intranuclear viral inclusions, numerous.

Conference Comment:  

In addition to discussing simian parvovirus, for which the contributor provided a good review, conference participants also discussed other parvoviruses of importance in veterinary medicine. Viruses in the family Parvoviridae are non enveloped, single-stranded DNA viruses that lack enzymes for DNA replication and thus require host cell DNA polymerase;3 hence, they replicate in host cell nuclei during the S phase of the cell division cycle. Their need to replicate in cells undergoing cell division determines the pathogenicity of the virus. Infections in fetuses or newborns during organogenesis can lead to serious defects, as the virus destroys developing tissues such as the cerebellum (such as in feline panleukopenia) and the myocardium (such as in canine parvovirus). In older animals, only rapidly dividing cells (hematopoietic precursors, lymphocytes and mucosal cells lining the gut) are affected.(3)

The family Parvoviridae is divided into two subfamilies, Parvovirinae and Densovirinae. Parvovirinae contains viruses of vertebrates, and Densovirinae viruses affect insects. The Parvovirinae subfamily is further divided into five genera: Parvovirus, Erythrovirus, Dependovirus, Amdovirus, and Bocavirus.(3) The following tables list parvoviruses of veterinary importance and the diseases associated with them:(3)

Genus Parvovirus

Virus	Disease
Feline Panleukopenia Virus	Generalized disease in kittens; panleukopenia; enteritis; in-utero or neonatal infection can cause cerebellar hypoplasia; raccoon, mink and coatimundi are also susceptible
Mink Enteritis Virus	Leukopenia; enteritis
Canine Parvovirus 2 (3 major variants: subtypes 2a, 2b, 2c)	Generalized disease in puppies; enteritis; myocarditis; lymphopenia
Porcine Parvovirus	Stillbirth, mummification, embryonic death, infertility (SMEDI); rare respiratory disease, vesicular disease and systemic disease of neonates
Rodent Parvoviruses (Mouse parvoviruses, minute virus of mice, Kilhams rat virus, Toolanss H-1 virus of rats)	Subclinical or persistent infection; fetal malformations; hemorrhagic syndrome in rats; Confounding effects on research; hamsters with hamster parvovirus develop periodontal and craniofacial deformities
Rabbit Parvoviruses (Lapine Parvovirus)	Usually no clinical signs; may produce disseminated infection, mild enteritis in young kits

Genus Erythrovirus

Virus	Disease
Non-Human Primate Parvoviruses (Simian Parvovirus, Rhesus Parvovirus, Cynomolgus Parvovirus)	Anemia; fetal abnormalities; elatedto human B19 virus

Genus Amdovirus

Virus	Disease
Aleutian Mink Disease Virus	Adults (primarily mink that are homozygous for Aleutian coat color, which is associated with a Chediak- Higashi type abnormality): Chronic immune complex disease; encephalopathy; Neonates: interstitial pneumonia

Genus Dependovirus

Virus	Disease
Goose Parvovirus	Hepatitis; myocarditis; myositis; lethal disease in 8-30 day old goslings
Duck Parvovirus	Hepatitis; myocarditis; myositis in Muscovy ducks

Genus Bocavirus

Virus	Disease
Bovine Parvovirus	Rarely associated with clinical disease; mild diarrhea in neonates
Canine Parvovirus 1 (Canine Minute Parvovirus)	Subclinical; rarely causes diarrhea or sudden death in neonates

Tables adapted from Fenners Veterinary Virology, 4th ed. 2011.³

References:

1. OSullivan MG, Anderson DC, Fikes JD, Bain FT, Carlson CS, Green SW, et al. Identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. J Clin Invest. 1994;93:15711576.
2. OSullivan MG, Anderson DK, Goodrich JA, Tulli H, Green SW, Young NS, et al. Experimental infection of cynomolgus monkeys with simian parvovirus. J Virol. 1997;71:45174521.
3. Parris CR. Parvoviridae. In: Maclachlan JN, Dubovi EJ, eds. Fenner's Veterinary Virology. 4th ed. New York, NY: Academic Press; 2011:225-235.
4. Simon MA. Simian parvoviruses: biology and implications for research. Comp Med. 2008;58:47-50.

Click the slide to view.

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2-1. Bone marrow

2-2. None marrow

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