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Human cytomegalovirus IE1 and IE2 proteins block apoptosis
1Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University, New Jersey 08544-1014, USA.
Abstract:
Human cytomegalovirus-infected fibroblasts are resistant to the induction of apoptosis by superinfection with a mutant adenovirus unable to produce the viral E1B 19-kDa protein that normally causes an E1A protein-mediated apoptotic response. Two cytomegalovirus gene products that block apoptosis were identified. The IE1 and IE2 proteins each inhibit the induction of apoptosis by tumor necrosis factor alpha or by the E1B 19-kDa-protein-deficient adenovirus but not by irradiation with UV light. Our results suggest a new physiological role for the IE1 and IE2 proteins in the human cytomegalovirus replication cycle.
Insights
Human cytomegalovirus (CMV) infection prevents apoptosis, a programmed cell death. CMV IE1 and IE2 proteins block apoptosis induced by certain viruses and TNF-alpha, suggesting a role in the CMV replication cycle.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Human cytomegalovirus (CMV) is a ubiquitous herpesvirus that can establish lifelong infections.
- Apoptosis, or programmed cell death, is a critical cellular process that can be triggered by various stimuli, including viral infections.
- Certain viruses, like adenovirus, utilize specific proteins (e.g., E1B 19-kDa protein) to evade apoptosis and promote viral replication.
Purpose of the Study:
- To investigate the mechanisms by which CMV-infected cells resist apoptosis.
- To identify specific CMV gene products involved in blocking apoptotic pathways.
- To elucidate the role of these proteins in the CMV replication cycle.
Main Methods:
- Superinfection of CMV-infected fibroblasts with a mutant adenovirus lacking the E1B 19-kDa protein.
- Assessing apoptosis induction using stimuli such as tumor necrosis factor alpha (TNF-alpha) and UV irradiation.
- Analyzing the expression and function of CMV immediate-early (IE) 1 and IE2 proteins in apoptosis inhibition.
Main Results:
- CMV-infected fibroblasts demonstrated resistance to apoptosis induced by superinfection with the E1B 19-kDa-deficient adenovirus.
- CMV IE1 and IE2 proteins were identified as key mediators of this anti-apoptotic effect.
- IE1 and IE2 proteins inhibited apoptosis induced by TNF-alpha and the adenovirus mutant, but not by UV irradiation.
Conclusions:
- CMV IE1 and IE2 proteins play a significant role in preventing apoptosis during CMV infection.
- These proteins contribute to the evasion of host cell death pathways, facilitating viral replication.
- The findings suggest a novel physiological function for IE1 and IE2 proteins within the CMV life cycle.