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Hematopoietic cells from CD155-transgenic mice express CD155 and support poliovirus replication ex vivo
1Department of Microbiology, Immunology and Parasitology, Lousiana State University Health Sciences Center, 1901 Perdido St, New Orleans, LA 70112, USA. mfreis@lsumc.edu
Abstract:
Despite identification of the poliovirus (PV) receptor (CD155), mechanisms by which this molecule mediates paralytic disease remain obscure. Unanswered questions include CD155 localization in human tissues, the nature of cells supporting the first round of replication, identity of nonneural replication sites, and route of entry into the CNS. In earlier work, we showed that CD155 is expressed on primary human monocytes and that these cells support low, but statistically significant, levels of PV replication ex vivo without prior culturing. We hypothesize that monocytes support PV replication in vivo and that they contribute to pathogenesis. In the current study, we tested whether CD155-transgenic mouse hematopoietic cells express cell surface CD155 and whether these cells support PV replication. We found that the majority of monocyte/macrophages from peritoneal washes express CD155. In addition, 26-32% of CD155-transgenic bone marrow and spleen cells express CD155 on monocyte/macrophages, T cells and hematopoietic precursor cells. Various tissues supported PV replication without pre-culturing, however, pre-culturing or pre-treatment of mice with thioglycollate increased virus yield. These results are consistent with those from human cells and suggest that the CD155 transgenic mouse model is useful to help understand the role of hematopoietic cells in PV pathogenesis.
Insights
Poliovirus (PV) replication occurs in hematopoietic cells, including monocytes, which express the poliovirus receptor (CD155). This finding suggests a role for these cells in PV pathogenesis and disease.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- The poliovirus (PV) receptor, CD155, is known, but its role in paralytic disease is unclear.
- Key questions involve CD155 localization, initial replication sites, and central nervous system (CNS) entry routes.
- Previous studies showed CD155 on human monocytes, supporting low-level PV replication ex vivo.
Purpose of the Study:
- To investigate if CD155-transgenic mouse hematopoietic cells express CD155.
- To determine if these cells support PV replication.
- To explore the role of hematopoietic cells in PV pathogenesis.
Main Methods:
- Assessed CD155 expression on hematopoietic cells from CD155-transgenic mice.
- Quantified PV replication in various hematopoietic tissues ex vivo.
- Evaluated the effect of pre-culturing and thioglycollate treatment on virus yield.
Main Results:
- The majority of monocyte/macrophages from peritoneal washes expressed CD155.
- CD155 was found on 26-32% of bone marrow and spleen cells, including monocyte/macrophages, T cells, and hematopoietic precursors.
- Various tissues supported PV replication, with increased yields after pre-culturing or thioglycollate treatment.
Conclusions:
- Hematopoietic cells, including monocytes, express CD155 and support PV replication.
- The CD155 transgenic mouse model is valuable for studying hematopoietic cell involvement in PV pathogenesis.
- Findings align with human cell data, supporting the hypothesis of monocyte contribution to PV disease.