title: Myocarditis, disseminated infection, and early viral persistence following experimental coxsackievirus B infection of cynomolgus monkeys.
abstract: Coxsackievirus B (CVB) infection is a common cause of acute viral myocarditis. The clinical presentation of myocarditis caused by this enterovirus is highly variable, ranging from mildly symptoms to complete hemodynamic collapse. These variations in initial symptoms and in the immediate and long term outcomes of this disease have impeded development of effective treatment strategies. Nine cynomolgus monkeys were inoculated with myocarditic strains of CVB. Virological studies performed up to 28 days post-inoculation demonstrated the development of neutralizing antibody in all animals, and the presence of CVB in plasma. High dose intravenous inoculation (n = 2) resulted in severe disseminated disease, while low dose intravenous (n = 6) or oral infection (1 animal) resulted in clinically unapparent infection. Transient, minor, echocardiographic abnormalities were noted in several animals, but no animals displayed signs of significant acute cardiac failure. Although viremia rapidly resolved, signs of myocardial inflammation and injury were observed in all animals at the time of necropsy, and CVB was detected in postmortem myocardial specimens up to 28 days PI. This non-human primate system replicates many features of illness in acute coxsackievirus myocarditis and demonstrates that myocardial involvement may be common in enteroviral infection; it may provide a model system for testing of treatment strategies for enteroviral infections and acute coxsackievirus myocarditis.
authors.affiliation: Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Cheryl E
authors.initials: CE
authors.lastname: Cammock
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Halnon
authors.forename: Jill
authors.initials: J
authors.lastname: Skoczylas
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bohm
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
authors.forename: Chi
authors.initials: C
authors.lastname: Lai
authors.forename: Paul A
authors.initials: PA
authors.lastname: Krogstad
mesh_terms: D000284:Administration, Oral; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D003384:Coxsackievirus Infections / Q000150:complications / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D004452:Echocardiography; D029822:Enterovirus B, Human / Q000502:physiology; D005260:Female; D056724:Immunity, Humoral; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D009205:Myocarditis / Q000150:complications / Q000276:immunology / Q000473:pathology* / Q000821:virology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
references.citation: Am J Cardiovasc Pathol. 1987 Jan;1(1):3-14
references.pmid: 3455232
references.citation: J Am Coll Cardiol. 2000 Nov 15;36(6):1920-6
references.pmid: 11092665
references.citation: J Immunol. 2011 Jan 1;186(1):341-9
references.pmid: 21131427
references.citation: Rev Med Virol. 2005 Jan-Feb;15(1):17-27
references.pmid: 15386590
references.citation: Toxicol Pathol. 2010 Jun;38(4):642-57
references.pmid: 20448082
references.citation: J Am Assoc Lab Anim Sci. 2008 Jan;47(1):22-5
references.pmid: 18210994
references.citation: Lancet. 1986 May 17;1(8490):1120-3
references.pmid: 2871380
references.citation: J Med Primatol. 1980;9(5):323-4
references.pmid: 6255160
references.citation: MMWR Morb Mortal Wkly Rep. 2008 May 23;57(20):553-6
references.pmid: 18496504
references.citation: Eur Heart J. 2008 Sep;29(17):2073-82
references.pmid: 18617482
references.citation: Infect Immun. 1981 Jan;31(1):470-9
references.pmid: 6260666
references.citation: J Med Virol. 2002 Feb;66(2):241-5
references.pmid: 11782934
references.citation: Biochem Pharmacol. 2012 Jan 15;83(2):185-92
references.pmid: 21889497
references.citation: Curr Protoc Immunol. 2013;Chapter 15:Unit 15.14.1-51
references.pmid: 23564686
references.citation: Circulation. 1994 Jun;89(6):2582-9
references.pmid: 8205668
references.citation: J Am Coll Cardiol. 2003 Aug 6;42(3):466-72
references.pmid: 12906974
references.citation: Pediatr Cardiol. 2008 Jul;29(4):834-7
references.pmid: 18158605
references.citation: J Virol. 2001 Mar;75(5):2377-87
references.pmid: 11160741
references.citation: Diagn Mol Pathol. 2002 Dec;11(4):212-21
references.pmid: 12459637
references.citation: ASAIO J. 2008 Sep-Oct;54(5):554-5
references.pmid: 18812754
references.citation: J Med Virol. 2002 Aug;67(4):555-62
references.pmid: 12116004
references.citation: Antimicrob Agents Chemother. 2012 Sep;56(9):4838-44
references.pmid: 22751539
references.citation: Med Microbiol Immunol. 2004 May;193(2-3):65-9
references.pmid: 14722762
references.citation: Pediatr Infect Dis J. 2008 Jul;27(7):668-9
references.pmid: 18536618
references.citation: Curr Top Microbiol Immunol. 2008;323:275-92
references.pmid: 18357775
references.citation: Jpn Circ J. 1983 Jan;47(1):59-66
references.pmid: 6298479
references.citation: Prog Cardiovasc Dis. 2006 Jul-Aug;49(1):42-57
references.pmid: 16867849
references.citation: J Virol. 1998 Nov;72(11):8578-85
references.pmid: 9765396
references.citation: J Med Primatol. 1978;7(2):119-21
references.pmid: 213604
references.citation: Paediatr Drugs. 2004;6(1):1-10
references.pmid: 14969566
references.citation: J Virol. 2002 May;76(9):4430-40
references.pmid: 11932410
references.citation: N Engl J Med. 1995 Aug 3;333(5):269-75
references.pmid: 7596370
references.citation: J Virol. 1996 Nov;70(11):7811-8
references.pmid: 8892902
references.citation: J Am Coll Cardiol. 1992 Mar 15;19(4):864-9
references.pmid: 1312100
references.citation: Arch Dis Child Fetal Neonatal Ed. 2010 May;95(3):F206-12
references.pmid: 20444813
references.citation: Lancet. 2012 Feb 25;379(9817):738-47
references.pmid: 22185868
references.citation: Immunogenetics. 2009 Mar;61(3):177-87
references.pmid: 19107381
references.citation: N Engl J Med. 2000 Mar 9;342(10):690-5
references.pmid: 10706898