title: Experimental infection of rhesus macaques and common marmosets with a European strain of West Nile virus.
abstract: West Nile virus (WNV) is a mosquito-borne flavivirus that infects humans and other mammals. In some cases WNV causes severe neurological disease. During recent years, outbreaks of WNV are increasing in worldwide distribution and novel genetic variants of the virus have been detected. Although a substantial amount of data exists on WNV infections in rodent models, little is known about early events during WNV infection in primates, including humans. To gain a deeper understanding of this process, we performed experimental infections of rhesus macaques and common marmosets with a virulent European WNV strain (WNV-Ita09) and monitored virological, hematological, and biochemical parameters. WNV-Ita09 productively infected both monkey species, with higher replication and wider tissue distribution in common marmosets compared to rhesus macaques. The animals in this study however, did not develop clinical signs of WNV disease, nor showed substantial deviations in clinical laboratory parameters. In both species, the virus induced a rapid CD56dimCD16bright natural killer response, followed by IgM and IgG antibody responses. The results of this study show that healthy rhesus macaques and common marmosets are promising animal models to study WNV-Ita09 infection. Both models may be particularly of use to evaluate potential vaccine candidates or to investigate WNV pathogenesis.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Babs E
authors.initials: BE
authors.lastname: Verstrepen
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fagrouch
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Melanie
authors.initials: M
authors.lastname: van Heteren
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Hester
authors.initials: H
authors.lastname: Buitendijk
authors.affiliation: Animal Science Department, Division of Pathology and Microbiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Haaksma
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Beenhakker
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.affiliation: Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Richner
authors.affiliation: Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Willy M
authors.initials: WM
authors.lastname: Bogers
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
authors.affiliation: Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Chabierski
authors.affiliation: Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ulbert
authors.affiliation: Animal Science Department, Division of Pathology and Microbiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Ivanela
authors.initials: I
authors.lastname: Kondova
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019002:CD56 Antigen / Q000032:analysis; D002144:Callithrix; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology; D008253:Macaca mulatta; D017452:Receptors, IgG / Q000032:analysis; D014901:West Nile Fever / Q000473:pathology* / Q000821:virology*; D014902:West Nile virus / Q000254:growth & development
chemical_list: D000914:Antibodies, Viral; D019002:CD56 Antigen; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017452:Receptors, IgG
references.citation: Front Immunol. 2013 Feb 18;4:32
references.pmid: 23423644
references.citation: J Clin Microbiol. 2000 Nov;38(11):4066-71
references.pmid: 11060069
references.citation: J Infect Dis. 2013 Oct 1;208(7):1086-92
references.pmid: 23821721
references.citation: Euro Surveill. 2009 Oct 08;14(40):
references.pmid: 19822123
references.citation: Expert Rev Anti Infect Ther. 2013 May;11(5):479-87
references.pmid: 23627854
references.citation: Euro Surveill. 2012 Sep 06;17(36):20260
references.pmid: 22971328
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6694-9
references.pmid: 16617103
references.citation: Emerg Infect Dis. 2001 Jul-Aug;7(4):714-21
references.pmid: 11585537
references.citation: Am J Hyg. 1958 Sep;68(2):106-19
references.pmid: 13571225
references.citation: J Infect Dis. 2004 Feb 15;189(4):669-76
references.pmid: 14767821
references.citation: J Immunol. 1977 Oct;119(4):1452-6
references.pmid: 19536
references.citation: Arch Virol. 2012 Feb;157(2):363-8
references.pmid: 22139354
references.citation: Nature. 2012 Nov 1;491(7422):31-3
references.pmid: 23128209
references.citation: J Med Primatol. 2012 Oct;41(5):289-96
references.pmid: 22775469
references.citation: J Immunol Methods. 2012 Dec 14;386(1-2):10-21
references.pmid: 22955212
references.citation: J Infect Dis. 2010 Jan 1;201(1):2-4
references.pmid: 19961306
references.citation: J Infect Dis. 2011 Feb 1;203(3):344-7
references.pmid: 21208926
references.citation: Comp Med. 2003 Aug;53(4):383-92
references.pmid: 14524414
references.citation: J Gen Virol. 2011 Oct;92(Pt 10):2272-2280
references.pmid: 21697346
references.citation: Clin Infect Dis. 2007 Oct 15;45(8):1039-46
references.pmid: 17879923
references.citation: Eur J Clin Microbiol Infect Dis. 2004 Mar;23(3):147-56
references.pmid: 14986160
references.citation: Virology. 2006 Nov 10;355(1):44-51
references.pmid: 16904151
references.citation: J Virol. 2013 Feb;87(4):1926-36
references.pmid: 23221549
references.citation: J Immunol. 2009 Aug 15;183(4):2610-21
references.pmid: 19635919
references.citation: J Neuropathol Exp Neurol. 1956 Oct;15(4):448-60
references.pmid: 13367865
references.citation: Emerg Infect Dis. 2005 Aug;11(8):1174-9
references.pmid: 16102303
references.citation: Am J Trop Med Hyg. 2010 Jun;82(6):1160-7
references.pmid: 20519618
references.citation: J Infect Dis. 2012 May 1;205(9):1476-7
references.pmid: 22438324
references.citation: Virol J. 2010 Jul 06;7:146
references.pmid: 20604940
references.citation: J Infect Dis. 2005 Jul 15;192(2):287-95
references.pmid: 15962223
references.citation: J Hyg (Lond). 1970 Sep;68(3):435-46
references.pmid: 4917916
references.citation: J Virol. 2004 Nov;78(22):12497-507
references.pmid: 15507637
references.citation: Expert Rev Anti Infect Ther. 2012 Jul;10(7):743-50
references.pmid: 22943398
references.citation: Euro Surveill. 2010 Mar 11;15(10):19508
references.pmid: 20403311
references.citation: Clin Vaccine Immunol. 2009 Sep;16(9):1332-7
references.pmid: 19641099
references.citation: PLoS Pathog. 2013 Feb;9(2):e1003168
references.pmid: 23544010
references.citation: BMC Immunol. 2010 Jan 20;11:3
references.pmid: 20089143
references.citation: PLoS One. 2013 Sep 23;8(9):e75910
references.pmid: 24086663
references.citation: Euro Surveill. 2009 Nov 05;14(44):
references.pmid: 19941775
references.citation: Euro Surveill. 2010 Aug 26;15(34):
references.pmid: 20807489
references.citation: Emerg Infect Dis. 2004 Apr;10(4):712-4
references.pmid: 15200866
references.citation: Virology. 2003 Jun 20;311(1):72-80
references.pmid: 12832204
references.citation: J Virol. 2011 Mar;85(6):2964-74
references.pmid: 21159871
references.citation: Blood. 2004 Sep 1;104(5):1482-9
references.pmid: 15150077
references.citation: Virology. 2003 Sep 15;314(1):190-5
references.pmid: 14517072
references.citation: Blood. 2012 Apr 26;119(17):3987-96
references.pmid: 22403260
references.citation: J Virol. 2007 Nov;81(21):11828-39
references.pmid: 17715236
references.citation: PLoS One. 2012;7(7):e40374
references.pmid: 22792293
references.citation: Emerg Infect Dis. 2005 Aug;11(8):1167-73
references.pmid: 16102302
references.citation: Arch Virol. 1983;75(1-2):71-86
references.pmid: 6299247
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12
references.pmid: 23401516
references.citation: J Med Virol. 2001 Dec;65(4):694-7
references.pmid: 11745933
references.citation: J Virol. 2006 Jan;80(1):119-29
references.pmid: 16352536
references.citation: Vaccine. 2011 Aug 26;29(37):6352-7
references.pmid: 21596075
references.citation: PLoS Negl Trop Dis. 2013 Jun 13;7(6):e2275
references.pmid: 23785537
references.citation: Virology. 1997 Jun 23;233(1):85-92
references.pmid: 9229928
references.citation: Vaccine. 2012 Oct 19;30(47):6656-64
references.pmid: 22959989
references.citation: Am J Trop Med Hyg. 2005 Mar;72(3):320-4
references.pmid: 15772329
references.citation: Brain Pathol. 2007 Oct;17(4):354-62
references.pmid: 17610522
references.citation: Nat Rev Microbiol. 2013 Feb;11(2):115-28
references.pmid: 23321534
references.citation: PLoS One. 2010 May 14;5(5):e10649
references.pmid: 20498839