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Updated: May 4, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Human cytomegalovirus suppresses Fas expression and function
Sepehr Seirafian1, Virginie Prod'homme1, Daniel Sugrue1
1Institute of Infection & Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
Abstract:
Human cytomegalovirus (HCMV) is known to evade extrinsic pro-apoptotic pathways not only by downregulating cell surface expression of the death receptors TNFR1, TRAIL receptor 1 (TNFRSF10A) and TRAIL receptor 2 (TNFRSF10B), but also by impeding downstream signalling events. Fas (CD95/APO-1/TNFRSF6) also plays a prominent role in apoptotic clearance of virus-infected cells, so its fate in HCMV-infected cells needs to be addressed. Here, we show that cell surface expression of Fas was suppressed in HCMV-infected fibroblasts from 24 h onwards through the late phase of productive infection, and was dependent on de novo virus-encoded gene expression but not virus DNA replication. Significant levels of the fully glycosylated (endoglycosidase-H-resistant) Fas were retained within HCMV-infected cells throughout the infection within intracellular membranous structures. HCMV infection provided cells with a high level of protection against Fas-mediated apoptosis. Downregulation of Fas was observed with HCMV strains AD169, FIX, Merlin and TB40.
Insights
Human cytomegalovirus (HCMV) suppresses cell surface Fas expression, a key apoptosis receptor, during infection. This viral immune evasion strategy protects infected cells from programmed cell death.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Human cytomegalovirus (HCMV) evades apoptosis by downregulating death receptors like TNFR1 and TRAIL receptors.
- Fas (CD95/APO-1/TNFRSF6) is crucial for clearing virus-infected cells via apoptosis.
- The fate of Fas during HCMV infection requires investigation.
Purpose of the Study:
- To investigate the impact of HCMV infection on cell surface Fas expression.
- To determine the mechanism and viral dependency of Fas downregulation.
- To assess the functional consequence of altered Fas expression on apoptosis.
Main Methods:
- Fibroblast infection with HCMV strains (AD169, FIX, Merlin, TB40).
- Analysis of cell surface Fas expression via flow cytometry.
- Intracellular Fas localization using microscopy and biochemical assays (endoglycosidase-H resistance).
- Assessment of apoptosis induction upon Fas stimulation.
Main Results:
- HCMV infection suppressed cell surface Fas expression starting 24 hours post-infection.
- Fas downregulation was dependent on de novo viral gene expression, not viral DNA replication.
- Intracellular retention of fully glycosylated Fas was observed in HCMV-infected cells.
- HCMV infection conferred significant protection against Fas-mediated apoptosis.
Conclusions:
- HCMV actively downregulates cell surface Fas expression to evade apoptosis.
- Intracellular retention of Fas contributes to viral immune evasion.
- This mechanism protects HCMV-infected cells from Fas-induced cell death across multiple viral strains.
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