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Pathogenesis of poliovirus infection in PVRTg mice: poliovirus replicates in peritoneal macrophages
A M Buisman1, J A J Sonsma1, M G S van Wijk2
1Research Laboratory for Infectious Diseases, National Institute for Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands.
Abstract:
The pathogenesis of poliovirus infection, responsible for the induction of a poliovirus-specific mucosal immune response following intraperitoneal (i.p.) inoculation of virus in mice transgenic for the poliovirus receptor (PVRTg mice), was studied. Following inoculation of poliovirus, replication was determined by increase in virus titre (TCID(50)) and by PCR of poliovirus-specific negative-strand RNA in peritoneal macrophages, mesenteric lymph nodes, Peyer's patches, duodenum, brain, kidney and liver. The presence of poliovirus antigens in several cell types was detected by immunolabelling. It was demonstrated that poliovirus replicated in the peritoneal macrophages of PVRTg mice, since the virus titre in peritoneal cells was increased compared to the titre in the inoculum. Negative-strand RNA was detected in these cells and most of the poliovirus-immunostained cells had the morphology of macrophages and expressed the macrophage-specific markers CD86 and M1/70 on their surface. Furthermore, in peritoneal lavage, poliovirus was also present in CD19(+) B cells, but not in dendritic or T cells. Moreover, poliovirus was detected in macrophage-like cells in the lamina propria of the intestine, but not in epithelial cells. Replication of poliovirus in mesenteric lymph nodes, Peyer's patches and brain was followed by excretion of virus in the faeces. This suggests that the virus is transported due to migration of macrophages from the peritoneal cavity to mesenteric lymph nodes and the lamina propria of Peyer's patches. It is likely that this route is responsible for the induction of virus-specific IgA in the gut.
Insights
Poliovirus replicates in peritoneal macrophages of transgenic mice, spreading to lymph nodes and gut. This macrophage migration is key to initiating the gut
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Poliovirus causes significant human disease, necessitating understanding its infection pathways.
- Mucosal immune responses are crucial for controlling viral infections, especially in the gut.
Purpose of the Study:
- To investigate the early pathogenesis of poliovirus infection in poliovirus receptor transgenic mice.
- To identify the primary cell types and routes involved in poliovirus replication and dissemination following intraperitoneal inoculation.
Main Methods:
- Inoculation of poliovirus into poliovirus receptor transgenic mice.
- Quantification of viral replication via virus titration (TCID50) and PCR detection of negative-strand RNA.
- Immunolabelling to detect poliovirus antigens and identify cell surface markers (CD86, M1/70, CD19).
Main Results:
- Poliovirus replicated effectively in peritoneal macrophages, confirmed by increased virus titre and presence of viral RNA.
- Macrophages were identified as the primary infected cells in the peritoneal cavity, with poliovirus also found in B cells.
- Virus was detected in macrophage-like cells in the intestinal lamina propria, but not epithelial cells, preceding fecal excretion.
Conclusions:
- Peritoneal macrophages are an early site of poliovirus replication and a likely vehicle for viral transport to mesenteric lymph nodes and Peyer's patches.
- Macrophage migration from the peritoneal cavity to the gut lamina propria is a critical route for poliovirus dissemination and induction of gut-specific IgA response.
