Coxsackie B virus infection of mice: inoculation by the oral route protects the pancreas from damage, but not from infection.
The pathogenesis of coxsackie B virus (CVB) infections is generally studied in mice by intraperitoneal (i.p.) injection, whereas the gastrointestinal tract is the natural porte d'entrée in humans. The present study was undertaken to compare systematically the influence of infection route on morbidity and pathology. Swiss Albino mice were infected with CVB3 (Nancy) at different doses (5 x 10(3), 5 x 10(5), 5 x 10(7), 5 x 10(9) TCID50), given either i.p. or orally. Virus could be isolated from several organs (heart, spleen and pancreas), indicating systemic infection, irrespective of the infection route. Virus titres were 1-2 logs higher after i.p. infection, but kinetics were largely independent of infection route. Organs became negative for virus isolation after 21 days, with the exception of spleen tissue, which remained positive for up to 49 days. Thereafter, virus was detected only by immunohistochemistry and PCR up to 98 days post-infection (oral route). Histopathology showed mild inflammation and necrosis in heart tissue of all mice during the acute phase, with repair at later stages. Strikingly, pancreatic lesions were confined to the exocrine pancreas and observed only after i.p. infection. Under all experimental conditions, the pancreatic islets were spared. In contrast, immunohistochemistry showed the presence of viral VP1, protein 3A and alpha interferon (IFN-alpha) in exocrine as well as endocrine pancreas of all mice, irrespective of route and dose of infection. It is concluded that infection via the oral route protects the pancreas from damage, but not from infection, a process in which IFN-alpha is not the only factor involved.
Bopegamage
Shubhada
S
Department of Virology, Slovak Medical University, Limbova 12, 83303 Bratislava, Slovak Republic.
Kovacova
Jana
J
Department of Virology, Slovak Medical University, Limbova 12, 83303 Bratislava, Slovak Republic.
Vargova
Agnesa
A
Department of Virology, Slovak Medical University, Limbova 12, 83303 Bratislava, Slovak Republic.
Motusova
Jana
J
Department of Virology, Slovak Medical University, Limbova 12, 83303 Bratislava, Slovak Republic.
Petrovicova
Anna
A
Department of Virology, Slovak Medical University, Limbova 12, 83303 Bratislava, Slovak Republic.
Benkovicova
Maria
M
Institute of Pathology, Derer's Hospital and Clinic, Limbova 5, 83301 Bratislava, Slovak Republic.
Gomolcak
Pavol
P
Institute of Pathology, Derer's Hospital and Clinic, Limbova 5, 83301 Bratislava, Slovak Republic.
Bakkers
Judith
J
Virology Section, Department of Medical Microbiology, Radboud University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
van Kuppeveld
Frank
F
Virology Section, Department of Medical Microbiology, Radboud University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Melchers
Willem J G
WJG
Virology Section, Department of Medical Microbiology, Radboud University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Galama
Jochem M
JM
Virology Section, Department of Medical Microbiology, Radboud University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000302:isolation & purification / Q000472:pathogenicity*; D006321:Heart / Q000821:virology; D007150:Immunohistochemistry; D007249:Inflammation; D007274:Injections, Intraperitoneal; D016898:Interferon-alpha / Q000032:analysis; D007421:Intestine, Small / Q000737:chemistry / Q000473:pathology / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010179:Pancreas / Q000737:chemistry / Q000473:pathology* / Q000821:virology*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D013154:Spleen / Q000821:virology; D014764:Viral Proteins / Q000032:analysis
D016898:Interferon-alpha; D012367:RNA, Viral; D014764:Viral Proteins