ArticlePLoS pathogens2005
A surface groove essential for viral Bcl-2 function during chronic infection in vivo.
Article in PLoS pathogens, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- Kaposi's sarcoma-associated herpesvirus induces mitochondrial fission to evade host immune responses and promote viral production.Nature microbiology · 2025Article
- Inhibition of BAK-mediated apoptosis by the BH3-only protein BNIP5.Cell death and differentiation · 2025Article
- The unappreciated role of developing B cells in chronic gammaherpesvirus infections.PLoS pathogens · 2024Review
- Epstein-Barr Virus Encoded BCL2, BHRF1, Downregulates Autophagy by Noncanonical Binding of BECN1.Biochemistry · 2023Article
- The evolution of regulated cell death pathways in animals and their evasion by pathogens.Physiological reviews · 2022Review
- Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective.Frontiers in molecular biosciences · 2022Review
- Designing BH3-Mimetic Peptide Inhibitors for the Viral Bcl-2 Homologues A179L and BHRF1: Importance of Long-Range Electrostatic Interactions.ACS omega · 2021Article
- Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain.Biomolecules · 2020Article
- Autophagy Genes Enhance Murine Gammaherpesvirus 68 Reactivation from Latency by Preventing Virus-Induced Systemic Inflammation.Cell host & microbe · 2016Article
- Viral Bcl-2 Encoded by the Kaposi's Sarcoma-Associated Herpesvirus Is Vital for Virus Reactivation.Journal of virology · 2015Article
- Identification of the Essential Role of Viral Bcl-2 for Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.Journal of virology · 2015Article
- Yeast as a tool for studying proteins of the Bcl-2 family.Microbial cell (Graz, Austria) · 2015Review
- Novel functions of viral anti-apoptotic factors.Nature reviews. Microbiology · 2015Review
- Targeting γ-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy.The Journal of biological chemistry · 2014Article
- A gammaherpesvirus Bcl-2 ortholog blocks B cell receptor-mediated apoptosis and promotes the survival of developing B cells in vivo.PLoS pathogens · 2014Article
- Article
- Disruption of Bcl-2 and Bcl-xL by viral proteins as a possible cause of cancer.Infectious agents and cancer · 2014Review
- Structural biology of the Bcl-2 family and its mimicry by viral proteins.Cell death & disease · 2013Review
- The C-terminal region of Rift Valley fever virus NSm protein targets the protein to the mitochondrial outer membrane and exerts antiapoptotic function.Journal of virology · 2013Article
- Modulation of Immune System by Kaposi's Sarcoma-Associated Herpesvirus: Lessons from Viral Evasion Strategies.Frontiers in microbiology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
Antiapoptotic Bcl-2 family proteins inhibit apoptosis in cultured cells by binding BH3 domains of proapoptotic Bcl-2 family members via a hydrophobic BH3 binding groove on the protein surface. We investigated the physiological importance of the BH3 binding groove of an antiapoptotic Bcl-2 protein in mammals in vivo by analyzing a viral Bcl-2 family protein. We show that the gamma-herpesvirus 68 (gammaHV68) Bcl-2 family protein (gammaHV68 v-Bcl-2), which is known to inhibit apoptosis in cultured cells, inhibits both apoptosis in primary lymphocytes and Bax toxicity in yeast. Nuclear magnetic resonance determination of the gammaHV68 v-Bcl-2 structure revealed a BH3 binding groove that binds BH3 domain peptides from proapoptotic Bcl-2 family members Bax and Bak via a molecular mechanism shared with host Bcl-2 family proteins, involving a conserved arginine in the BH3 peptide binding groove. Mutations of this conserved arginine and two adjacent amino acids to alanine (SGR to AAA) within the BH3 binding groove resulted in a properly folded protein that lacked the capacity of the wild-type gammaHV68 v-Bcl-2 to bind Bax BH3 peptide and to block Bax toxicity in yeast. We tested the physiological importance of this v-Bcl-2 domain during viral infection by engineering viral mutants encoding a v-Bcl-2 containing the SGR to AAA mutation. This mutation resulted in a virus defective for both efficient reactivation of gammaHV68 from latency and efficient persistent gammaHV68 replication. These studies demonstrate an essential functional role for amino acids in the BH3 peptide binding groove of a viral Bcl-2 family member during chronic infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.