Coxsackie B virus infection of mice: inoculation by the oral route protects the pancreas from damage, but not from infection

Abstract

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.

Sex-Dependent Intestinal Replication of an Enteric Virus

“…injection models bypass the first stage of infection in the gastrointestinal tract. Relatively few studies have used oral inoculation of mice with coxsackievirus (19)(20)(21)(22)(23). Therefore, CVB3 replication and factors that influence viral replication in the intestine remain poorly understood.…”

Expression of Human Decay-Accelerating Factor on Intestinal Epithelium of Transgenic Mice Does Not Facilitate Infection by the Enteral Route

“…Although infection can be established by the enteral (oral [p.o.]) route in some murine models (15,16), the gastrointestinal tract has been reported to act as a barrier to infection, particularly beyond the neonatal period (17). Consistent with the idea of an intestinal barrier, our own experience has been that infection by the enteral route requires virus doses much higher (10,000-fold or more) than those needed to infect mice by intraperitoneal injection (unpublished data; see Fig.…”

Inoculation of the attenuated Coxsackievirus B3 Sabin3-like strain induces a protection against virulent CVB3 Nancy and CVB4 E2 strains in Swiss mice by both oral and intraperitoneal routes

“…In fact, a single inoculation of the mutant Sabin3-like by i.p route protected all mice challenged 16 days later with a virulent CVB3 and CVB4 E2 which induced, respectively, myocarditis and pancreatitis in the unprotected control mice. Heart and pancreatic damages due to viral CVB3 and CVB4 replication have been demonstrated to be clearly evident at 10 days post-infection (Tracy et al 1992;Tu et al 1995;Bopegamage et al 2003Bopegamage et al , 2005Jaidane et al 2006). However, one mouse immunized with the attenuated Sabin3-like strain, developed pancreatitis after challenge by i.p route with CVB4 E2.…”