Related Experiment Videos
Herpesviral proteins regulating apoptosis
1Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany.
Abstract:
The induction of apoptosis of virus-infected cells is an important defense mechanism of the host. Apoptosis of an infected cell can be induced cell autonomously as a consequence of viral replication or can be mediated by CTLs attacking the infected cells. Herpesviruses have developed different strategies to interfere with cell-autonomous apoptosis and to block CTL-induced apoptosis mediated by death receptors such as Fas and TRAIL. Herpesviruses, which establish a lifelong persistence in the infected host, can be found principally in two different conditions, episomal persistence with a limited number of genes expressed and lytic replication with expression of almost all genes. To meet the need of the virus to enhance survival of the infected cell, herpesviruses have evolved different strategies that function during both episomal persistence and lytic replication. Herpesviruses, which encode 70 to more than 200 genes have incorporated cell homologous antiapoptotic genes, they code for multifunctional genes that can also regulate apoptosis, and, finally, they modulate the expression of cellular apoptosis-regulating genes to favor survival of the infected cells. Viral interference with host cell apoptosis enhances viral replication, facilitates virus spread and persistence, and may promote the development of virus-induced cancer.
Insights
Herpesviruses evade host defenses by blocking apoptosis, programmed cell death. This viral strategy enhances replication, spread, and persistence, potentially leading to cancer.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Apoptosis is a crucial host defense against viral infections, eliminating infected cells.
- Herpesviruses employ sophisticated mechanisms to subvert both cell-autonomous and CTL-mediated apoptosis.
- Understanding these viral strategies is key to combating persistent infections and associated diseases.
Purpose of the Study:
- To elucidate the diverse strategies herpesviruses use to inhibit host cell apoptosis.
- To explore how herpesviruses manipulate apoptosis during both latent (episomal) and lytic replication phases.
- To investigate the link between viral interference with apoptosis and disease pathogenesis, including cancer.
Main Methods:
- Analysis of viral gene expression during different replication states.
- Identification and characterization of viral anti-apoptotic genes and their cellular homologs.
- Investigation of viral modulation of host cell apoptosis pathways, including death receptor signaling (Fas, TRAIL).
Main Results:
- Herpesviruses encode numerous genes that interfere with apoptosis, including anti-apoptotic genes and multifunctional proteins.
- Viruses actively modulate cellular apoptosis-regulating genes to promote infected cell survival.
- Viral evasion of apoptosis is critical for efficient viral replication, spread, and long-term persistence.
Conclusions:
- Herpesviruses possess multifaceted strategies to overcome host apoptotic defenses.
- Inhibition of apoptosis by herpesviruses is essential for viral lifecycle completion and pathogenesis.
- Targeting viral anti-apoptotic mechanisms may offer therapeutic avenues for herpesvirus infections and related cancers.