Related Experiment Videos
Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice
Abstract:
The in vitro induction of procoagulant activity (PCA) in murine peripheral blood mononuclear cells (PBM) by murine hepatitis virus type 3 (MHV-3) correlates with the disease susceptibility in three strains of mice. PBM from BALB/c mice, a strain in which MHV-3 infection results in fatal acute fulminant hepatitis, responds to the virus with a robust PCA response, whereas PBM from C3H/St mice, a strain which develops mild acute hepatitis followed by chronic hepatitis, only exhibit a modest PCA response. In contrast, PBM from A/J mice, a strain fully resistant to MHV-3, generate no increase in PCA above control levels. The induction phase of MHV-3 PCA is rapid, with an increase within 1-1.5 h, with maximum activity at 18h, and it precedes MHV-3 replication in either 17 CL1 cells, a fully permissive cell line, or in monocytes from these strains of mice. The PCA response of BALB/c PBM exceeds the response to any other known stimulus. No induction occurs upon direct stimulation of monocytes by MHV-3, but in the presence of lymphocyte collaboration, the PCA response is observed first at a lymphocyte:monocyte ratio of 2:1 and reaches a maximum as the lymphocyte:monocyte ratio approaches 4:1. This response appears to provide a functional marker for susceptibility to MHV-3 infection in inbred strains of mice and could be important in the pathogenesis of MHV-3-induced disease.
Insights
Murine hepatitis virus type 3 (MHV-3) induces procoagulant activity (PCA) in mouse immune cells, with higher PCA correlating to greater disease susceptibility. This PCA response, dependent on lymphocyte-monocyte interaction, serves as a marker for MHV-3 infection severity.
Area of Science:
- Immunology
- Virology
- Pathogenesis
Background:
- Murine hepatitis virus type 3 (MHV-3) infection severity varies across mouse strains.
- Procoagulant activity (PCA) is a measure of blood clotting potential.
Purpose of the Study:
- To investigate the relationship between MHV-3 induction of PCA in peripheral blood mononuclear cells (PBM) and mouse strain susceptibility to MHV-3 infection.
- To characterize the kinetics and cellular requirements of MHV-3-induced PCA.
Main Methods:
- In vitro induction of PCA in PBM from different mouse strains (BALB/c, C3H/St, A/J) upon MHV-3 exposure.
- Assessment of PCA levels at various time points post-infection.
- Evaluation of the role of lymphocyte-monocyte ratios in PCA induction.
Main Results:
- BALB/c mice, susceptible to fatal hepatitis, showed robust PCA induction.
- C3H/St mice, with mild hepatitis, exhibited modest PCA.
- A/J mice, resistant to MHV-3, displayed no significant PCA increase.
- PCA induction was rapid (1-1.5h), peaking at 18h, and preceded viral replication.
- Lymphocyte collaboration was essential for PCA induction, with optimal response at a 4:1 lymphocyte:monocyte ratio.
Conclusions:
- MHV-3-induced PCA in PBM is a functional marker for inbred mouse strain susceptibility to MHV-3 infection.
- The PCA response correlates with disease severity and may play a role in MHV-3 pathogenesis.