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Published on: October 7, 2011
Murine Cytomegalovirus and Human Cytomegalovirus Differ in Pyroptosis Induction in Different Cell Types During
Jessica J Carter1, Daniel H Schneider1, Arshaan M Hisamuddin1
1Viral Immunology Center, Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Abstract:
Pyroptosis is a proinflammatory programmed cell death (PCD) that protects the host against invading viruses. We previously reported that pyroptosis plays a prominent role in the pathogenesis of murine cytomegalovirus (MCMV) retinal necrosis using mice with MAIDS as a mouse model for AIDS-related human cytomegalovirus (HCMV) retinal necrosis. Because MCMV and HCMV exhibit species specificity, we sought to determine if pyroptosis induction extends to different cell types of murine or human origin. In vitro studies were therefore performed in which MCMV-infected mouse fibroblasts and mouse macrophages were compared with HCMV-infected human fibroblasts and human ARPE-19 cells for stimulation of caspase-1, gasdermin G (GSDMD), and interleukin (IL)-18 and/or IL-1β transcripts as markers for canonical pyroptosis operation. Whereas MCMV stimulated significant stimulation of pyroptosis-associated transcripts during productive replication of mouse fibroblasts and mouse macrophages, significant stimulation of these transcripts was not detected during HCMV productive replication of human fibroblasts or ARPE-19 cells. Additional studies using UV-inactivated MCMV suggested that virion tegument proteins are not involved in the induction of pyroptosis in MCMV-infected mouse fibroblasts. We conclude that pyroptosis induction during productive replication of MCMV or HCMV is host cell type-dependent and may extend to species specificity, although virus-encoded PCD suppressors must be considered.
Insights
Pyroptosis, a programmed cell death, is induced by mouse cytomegalovirus (MCMV) in mouse cells but not by human cytomegalovirus (HCMV) in human cells. This suggests pyroptosis induction is host cell-dependent and may be species-specific.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Pyroptosis is a pro-inflammatory programmed cell death (PCD) crucial for host defense against viral infections.
- Previous research implicated pyroptosis in murine cytomegalovirus (MCMV) retinal necrosis, using a mouse model for AIDS-related human cytomegalovirus (HCMV) retinal necrosis.
Purpose of the Study:
- To investigate whether pyroptosis induction by MCMV and HCMV extends to different murine and human cell types.
- To determine the role of host cell type and species specificity in pyroptosis induction during viral infection.
Main Methods:
- In vitro studies comparing MCMV-infected mouse fibroblasts/macrophages with HCMV-infected human fibroblasts/ARPE-19 cells.
- Analysis of pyroptosis markers: caspase-1, gasdermin G (GSDMD), and interleukin (IL)-18/IL-1β transcripts.
- Inclusion of studies with UV-inactivated MCMV to assess the role of virion tegument proteins.
Main Results:
- MCMV significantly stimulated pyroptosis-associated transcripts in mouse fibroblasts and macrophages during productive replication.
- HCMV did not significantly stimulate these transcripts in human fibroblasts or ARPE-19 cells during productive replication.
- Virion tegument proteins of MCMV were not implicated in pyroptosis induction in mouse fibroblasts.
Conclusions:
- Pyroptosis induction during MCMV and HCMV productive replication is dependent on the host cell type.
- The findings suggest pyroptosis induction may exhibit species specificity between MCMV and HCMV.
- The potential role of virus-encoded programmed cell death (PCD) suppressors in modulating pyroptosis must be considered.
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