Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1997 Jun;71(6):4517–4521. doi: 10.1128/jvi.71.6.4517-4521.1997

Experimental infection of cynomolgus monkeys with simian parvovirus.

M G O'Sullivan 1, D K Anderson 1, J A Goodrich 1, H Tulli 1, S W Green 1, N S Young 1, K E Brown 1
PMCID: PMC191672  PMID: 9151844

Abstract

Simian parvovirus is a recently discovered parvovirus that was first isolated from cynomolgus monkeys. It is similar to human B19 parvovirus in terms of virus genome, tropism for erythroid cells, and characteristic pathology in natural infections. Cynomolgus monkeys were infected with simian parvovirus to investigate their potential usefulness as an animal model of human B19 parvovirus. Six adult female cynomolgus monkeys were inoculated with purified simian parvovirus by the intravenous or intranasal route and monitored for evidence of clinical abnormalities; this included the preparation of complete hematological profiles. Viremia and simian parvovirus-specific antibody were determined in infected monkeys by dot blot and Western blot assays, respectively. Bone marrow was examined at necropsy 6, 10, or 15 days postinfection. All of the monkeys developed a smoldering, low-grade viremia that peaked approximately 10 to 12 days after inoculation. Peak viremia coincided with the appearance of specific antibody and was followed by sudden clearance of the virus and complete, but transient, absence of reticulocytes from the peripheral blood. Clinical signs were mild and involved mainly anorexia and slight weight loss. Infection was associated with a mild decrease in hemoglobin, hematocrit, and erythrocyte numbers. Bone marrow showed marked destruction of erythroid cells coincident with peak viremia. Our findings indicate that infection of healthy monkeys by simian parvovirus is self-limited and mild, with transient cessation of erythropoiesis. Our study has reproduced Koch's postulates and further shown that simian parvovirus infection of monkeys is almost identical to human B19 parvovirus infection of humans. Accordingly, this animal model may prove valuable in the study of the pathogenesis of B19 virus infection.

Full Text

The Full Text of this article is available as a PDF (384.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anand A., Gray E. S., Brown T., Clewley J. P., Cohen B. J. Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med. 1987 Jan 22;316(4):183–186. doi: 10.1056/NEJM198701223160403. [DOI] [PubMed] [Google Scholar]
  2. Anderson M. J., Higgins P. G., Davis L. R., Willman J. S., Jones S. E., Kidd I. M., Pattison J. R., Tyrrell D. A. Experimental parvoviral infection in humans. J Infect Dis. 1985 Aug;152(2):257–265. doi: 10.1093/infdis/152.2.257. [DOI] [PubMed] [Google Scholar]
  3. Anderson M. J., Jones S. E., Fisher-Hoch S. P., Lewis E., Hall S. M., Bartlett C. L., Cohen B. J., Mortimer P. P., Pereira M. S. Human parvovirus, the cause of erythema infectiosum (fifth disease)? Lancet. 1983 Jun 18;1(8338):1378–1378. doi: 10.1016/s0140-6736(83)92152-9. [DOI] [PubMed] [Google Scholar]
  4. Brown K. E., Anderson S. M., Young N. S. Erythrocyte P antigen: cellular receptor for B19 parvovirus. Science. 1993 Oct 1;262(5130):114–117. doi: 10.1126/science.8211117. [DOI] [PubMed] [Google Scholar]
  5. Brown K. E., Green S. W., Antunez de Mayolo J., Bellanti J. A., Smith S. D., Smith T. J., Young N. S. Congenital anaemia after transplacental B19 parvovirus infection. Lancet. 1994 Apr 9;343(8902):895–896. doi: 10.1016/s0140-6736(94)90011-6. [DOI] [PubMed] [Google Scholar]
  6. Brown K. E., Green S. W., O'Sullivan M. G., Young N. S. Cloning and sequencing of the simian parvovirus genome. Virology. 1995 Jul 10;210(2):314–322. doi: 10.1006/viro.1995.1348. [DOI] [PubMed] [Google Scholar]
  7. Brown K. E., Young N. S., Liu J. M. Molecular, cellular and clinical aspects of parvovirus B19 infection. Crit Rev Oncol Hematol. 1994 Feb;16(1):1–31. doi: 10.1016/1040-8428(94)90040-x. [DOI] [PubMed] [Google Scholar]
  8. Cossart Y. E., Field A. M., Cant B., Widdows D. Parvovirus-like particles in human sera. Lancet. 1975 Jan 11;1(7898):72–73. doi: 10.1016/s0140-6736(75)91074-0. [DOI] [PubMed] [Google Scholar]
  9. Daniel M. D., King N. W., Letvin N. L., Hunt R. D., Sehgal P. K., Desrosiers R. C. A new type D retrovirus isolated from macaques with an immunodeficiency syndrome. Science. 1984 Feb 10;223(4636):602–605. doi: 10.1126/science.6695172. [DOI] [PubMed] [Google Scholar]
  10. Finkel T. H., Török T. J., Ferguson P. J., Durigon E. L., Zaki S. R., Leung D. Y., Harbeck R. J., Gelfand E. W., Saulsbury F. T., Hollister J. R. Chronic parvovirus B19 infection and systemic necrotising vasculitis: opportunistic infection or aetiological agent? Lancet. 1994 May 21;343(8908):1255–1258. doi: 10.1016/s0140-6736(94)92152-0. [DOI] [PubMed] [Google Scholar]
  11. Frickhofen N., Abkowitz J. L., Safford M., Berry J. M., Antunez-de-Mayolo J., Astrow A., Cohen R., Halperin I., King L., Mintzer D. Persistent B19 parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1): a treatable cause of anemia in AIDS. Ann Intern Med. 1990 Dec 15;113(12):926–933. doi: 10.7326/0003-4819-113-12-926. [DOI] [PubMed] [Google Scholar]
  12. Hartwig N. G., Vermeij-Keers C., Van Elsacker-Niele A. M., Fleuren G. J. Embryonic malformations in a case of intrauterine parvovirus B19 infection. Teratology. 1989 Mar;39(3):295–302. doi: 10.1002/tera.1420390311. [DOI] [PubMed] [Google Scholar]
  13. Heberling R. L., Kalter S. S., Marx P. A., Lowry J. K., Rodriguez A. R. Dot immunobinding assay compared with enzyme-linked immunosorbent assay for rapid and specific detection of retrovirus antibody induced by human or simian acquired immunodeficiency syndrome. J Clin Microbiol. 1988 Apr;26(4):765–767. doi: 10.1128/jcm.26.4.765-767.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kajigaya S., Fujii H., Field A., Anderson S., Rosenfeld S., Anderson L. J., Shimada T., Young N. S. Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4646–4650. doi: 10.1073/pnas.88.11.4646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Katz V. L., McCoy M. C., Kuller J. A., Hansen W. F. An association between fetal parvovirus B19 infection and fetal anomalies: a report of two cases. Am J Perinatol. 1996 Jan;13(1):43–45. doi: 10.1055/s-2007-994201. [DOI] [PubMed] [Google Scholar]
  16. Kurtzman G., Frickhofen N., Kimball J., Jenkins D. W., Nienhuis A. W., Young N. S. Pure red-cell aplasia of 10 years' duration due to persistent parvovirus B19 infection and its cure with immunoglobulin therapy. N Engl J Med. 1989 Aug 24;321(8):519–523. doi: 10.1056/NEJM198908243210807. [DOI] [PubMed] [Google Scholar]
  17. Morey A. L., Keeling J. W., Porter H. J., Fleming K. A. Clinical and histopathological features of parvovirus B19 infection in the human fetus. Br J Obstet Gynaecol. 1992 Jul;99(7):566–574. doi: 10.1111/j.1471-0528.1992.tb13822.x. [DOI] [PubMed] [Google Scholar]
  18. Nigro G., Zerbini M., Krzysztofiak A., Gentilomi G., Porcaro M. A., Mango T., Musiani M. Active or recent parvovirus B19 infection in children with Kawasaki disease. Lancet. 1994 May 21;343(8908):1260–1261. doi: 10.1016/s0140-6736(94)92154-7. [DOI] [PubMed] [Google Scholar]
  19. O'Sullivan M. G., Anderson D. C., Fikes J. D., Bain F. T., Carlson C. S., Green S. W., Young N. S., Brown K. E. Identification of a novel simian parvovirus in cynomolgus monkeys with severe anemia. A paradigm of human B19 parvovirus infection. J Clin Invest. 1994 Apr;93(4):1571–1576. doi: 10.1172/JCI117136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Sullivan M. G., Anderson D. K., Lund J. E., Brown W. P., Green S. W., Young N. S., Brown K. E. Clinical and epidemiological features of simian parvovirus infection in cynomolgus macaques with severe anemia. Lab Anim Sci. 1996 Jun;46(3):291–297. [PubMed] [Google Scholar]
  21. Okumura A., Ichikawa T. Aseptic meningitis caused by human parvovirus B19. Arch Dis Child. 1993 Jun;68(6):784–785. doi: 10.1136/adc.68.6.784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pattison J. R. A new parvovirus: similarities between monkeys and humans. J Clin Invest. 1994 Apr;93(4):1354–1354. doi: 10.1172/JCI117110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Porter H. J., Quantrill A. M., Fleming K. A. B19 parvovirus infection of myocardial cells. Lancet. 1988 Mar 5;1(8584):535–536. doi: 10.1016/s0140-6736(88)91332-3. [DOI] [PubMed] [Google Scholar]
  24. Potter C. G., Potter A. C., Hatton C. S., Chapel H. M., Anderson M. J., Pattison J. R., Tyrrell D. A., Higgins P. G., Willman J. S., Parry H. F. Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19). J Clin Invest. 1987 May;79(5):1486–1492. doi: 10.1172/JCI112978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Saint-Martin J., Choulot J. J., Bonnaud E., Morinet F. Myocarditis caused by parvovirus. J Pediatr. 1990 Jun;116(6):1007–1008. doi: 10.1016/s0022-3476(05)80677-8. [DOI] [PubMed] [Google Scholar]
  26. Serjeant G. R., Serjeant B. E., Thomas P. W., Anderson M. J., Patou G., Pattison J. R. Human parvovirus infection in homozygous sickle cell disease. Lancet. 1993 May 15;341(8855):1237–1240. doi: 10.1016/0140-6736(93)91145-c. [DOI] [PubMed] [Google Scholar]
  27. Serjeant G. R., Topley J. M., Mason K., Serjeant B. E., Pattison J. R., Jones S. E., Mohamed R. Outbreak of aplastic crises in sickle cell anaemia associated with parvovirus-like agent. Lancet. 1981 Sep 19;2(8247):595–597. doi: 10.1016/s0140-6736(81)92739-2. [DOI] [PubMed] [Google Scholar]
  28. Weiland H. T., Vermey-Keers C., Salimans M. M., Fleuren G. J., Verwey R. A., Anderson M. J. Parvovirus B19 associated with fetal abnormality. Lancet. 1987 Mar 21;1(8534):682–683. doi: 10.1016/s0140-6736(87)90442-9. [DOI] [PubMed] [Google Scholar]
  29. Woolf A. D., Campion G. V., Chishick A., Wise S., Cohen B. J., Klouda P. T., Caul O., Dieppe P. A. Clinical manifestations of human parvovirus B19 in adults. Arch Intern Med. 1989 May;149(5):1153–1156. [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES