Summary auto-generated
This study investigated apoptosis (programmed cell death) induced by herpes simplex virus type 1 (HSV-1) in cord blood T lymphocytes. Researchers isolated CD4 and CD8 lymphocytes from newborn cord blood and infected them with HSV-1, then stimulated the cells with phytohaemagglutinin (PHA). Using multiple detection methods—agarose gel electrophoresis, DNA content analysis, and the TUNEL assay—they demonstrated that HSV-1 infection significantly increased apoptosis in both CD4 and CD8 lymphocytes compared to uninfected controls. Cell cycle analysis showed increased hypodiploid DNA content (indicating apoptosis) and decreased S-phase cells in infected lymphocytes. Notably, only 8-18% of apoptotic cells expressed detectable viral proteins (glycoprotein D and ICP27), suggesting apoptosis occurs in both infected and potentially uninfected bystander cells. Testing with blocking antibodies against Fas and Fas-ligand revealed these pathways do not mediate HSV-1-induced apoptosis, indicating a distinct mechanism. The findings suggest that HSV-1-induced apoptosis may contribute to immunosuppression in neonatal infections and impaired immune responses.
Key findings
- HSV-1 infection increased apoptosis in PHA-stimulated cord blood CD4 and CD8 lymphocytes by approximately 3-8 fold compared to mock-infected controls
- Apoptosis occurred in both HSV-1 antigen-expressing cells and cells lacking detectable viral proteins (8-18% of apoptotic cells expressed viral antigens)
- HSV-1 infection reduced cell proliferation, with decreased S-phase cells and increased hypodiploid (apoptotic) cell fractions
- The Fas-Fas-ligand pathway does not mediate HSV-1-induced apoptosis, indicating involvement of alternative apoptotic mechanisms
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Abstract
We investigated apoptosis induced by herpes simplex virus type 1 (HSV- 1) in cord blood T lymphocytes by using agarose gel electrophoresis, DNA content analysis and the terminal deoxytransferase (TdT)-mediated dUTP nick end-labelling (TUNEL) method. DNA fragmentation and the hypodiploid fraction in the cell cycle were both increased in HSV-1- infected CD4 and CD8 lymphocytes stimulated with phytohaemagglutinin (PHA) compared to mock-infected lymphocytes. The percentage of cells in the S phase was decreased in HSV-1-infected CD4 and CD8 lymphocytes. HSV-1 antigen, glycoprotein D (gD) and regulatory protein ICP27 were detected in 8-18% of the hypodiploid fraction of PHA-stimulated, HSV-1- infected lymphocytes. Apoptosis was induced not only in HSV-1 antigen- expressing cells but also in cells not expressing detectable viral proteins. Addition of anti-Fas antibody, anti-Fas-ligand antibody or a mixture of both had no effect on HSV-1-induced apoptosis, indicating that the Fas-Fas-ligand pathway did not contribute to HSV-1-induced apoptosis.