• DR5
• Herpesvirus
• KSHV
• restriction factor

• Humans
• Herpesvirus 8, Human/physiology
• Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism
• Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics
• Apoptosis
• Virus Replication
• Animals
• HEK293 Cells
• Herpesviridae/physiology
• TNF-Related Apoptosis-Inducing Ligand/metabolism
• Herpesvirus 4, Human

• 32188101 MOST | National Natural Science Foundation of China (NSFC)
• 2024M752464 China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)
• 2023YFC2306600 National Key R&D Program
• National Key R&D Program

• Common drugs and toxicity
• Genetic association
• Kidney and pancreatic cancers
• Statistics and bioinformatics analysis
• Transcriptomics profiles and shared key genes
• Type-2 diabetes

• Humans
• Diabetes Mellitus, Type 2/genetics
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/drug therapy
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/complications
• Computational Biology/methods
• Kidney Neoplasms/genetics
• Kidney Neoplasms/drug therapy
• Kidney Neoplasms/complications
• Gene Regulatory Networks
• Protein Interaction Maps
• DNA Methylation
• Biomarkers, Tumor/genetics
• Gene Expression Profiling
• Transcriptome
• Genomics/methods
• Gene Expression Regulation, Neoplastic
• Gene Ontology

• Humans
• Mumps virus/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Cell Line, Tumor
• Proto-Oncogene Proteins c-bcl-2
• Apoptosis/genetics

• School of Veterinary Science, Shiraz University

• pancreatic cancer
• survival
• survivin

• Humans
• Survivin
• Prognosis
• Inhibitor of Apoptosis Proteins
• Prospective Studies
• Biomarkers, Tumor
• Pancreatic Neoplasms/pathology

• Humans
• Apoptosis
• Endothelial Cells/metabolism
• Herpesvirus 8, Human/physiology
• Sarcoma, Kaposi
• Virus Latency/physiology

• R01 CA189986 NCI NIH HHS
• T32 AI007140 NIAID NIH HHS
• R01 CA217788 NCI NIH HHS
• T32 AI083203 NIAID NIH HHS
• R21 CA240479 NCI NIH HHS
• National Cancer Institute
• National Cancer Institute NCI
• NIH NIAID
• Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases

Primary effusion lymphoma (PEL) is a fatal B-cell lymphoma caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) infection. Inducing KSHV lytic replication that causes the death of host cells is an attractive treatment approach for PE; however, combination therapy inhibiting viral production is frequently needed to improve its outcomes. We have previously shown that the KSHV lytic protein K-bZIP can SUMOylate histone lysine demethylase 4A (KDM4A) at lysine 471 (K471) and this SUMOylation is required for virus production upon KSHV reactivation. Here, we demonstrate that SUMOylation of KDM4A orchestrates PEL cell survival, a major challenge for the success of PEL treatment; and cell movement and angiogenesis, the cell functions contributing to PEL cell extravasation and dissemination. Furthermore, integrated ChIP-seq and RNA-seq analyses identified interleukin-10 (IL-10), an immunosuppressive cytokine, as a novel downstream target of KDM4A. We demonstrate that PEL-induced angiogenesis is dependent on IL-10. More importantly, single-cell RNA sequencing (scRNA-seq) analysis demonstrated that, at the late stage of KSHV reactivation, KDM4A determines the fates of PEL cells, as evidenced by two distinct cell populations; one with less apoptotic signaling expresses high levels of viral genes and the other is exactly opposite, while KDM4A-K417R-expressing cells contain only the apoptotic population with less viral gene expression. Consistently, KDM4A knockout significantly reduced cell viability and virus production in KSHV-reactivated PEL cells. Since inhibiting PEL extravasation and eradicating KSHV-infected PEL cells without increasing viral load provide a strong rationale for treating PEL, this study indicates targeting KDM4A as a promising therapeutic option for treating PEL.

IMPORTANCE PEL is an aggressive and untreatable B-cell lymphoma caused by KSHV infection. Therefore, new therapeutic approaches for PEL need to be investigated. Since simultaneous induction of KSHV reactivation and apoptosis can directly kill PEL cells, they have been applied in the treatment of this hematologic malignancy and have made progress. Epigenetic therapy with histone deacetylase (HDAC) inhibitors has been proved to treat PEL. However, the antitumor efficacies of HDAC inhibitors are modest and new approaches are needed. Following our previous report showing that the histone lysine demethylase KDM4A and its SUMOylation are required for lytic reactivation of KSHV in PEL cells, we further investigated its cellular function. Here, we found that SUMOylation of KDM4A is required for the survival, movement, and angiogenesis of lytic KSHV-infected PEL cells. Together with our previous finding showing the importance of KDM4A SUMOylation in viral production, KDM4A can be a potential therapeutic target for PEL.

• KDM4A
• Kaposi's sarcoma-associated herpesvirus (KSHV)
• SUMOylation
• histone lysine demethylase (KDM)
• primary effusion lymphoma (PEL)

• Kaposi’s sarcoma
• angiogenesis
• human herpes virus 8
• immune modulation
• immunosuppression
• oncogenesis
• skin cancer

• alternative splicing
• cancer cells
• immune cells

• apoptosis
• cell death
• infection
• necroptosis
• pyroptosis

• Animals
• Cell Death/physiology
• Host-Pathogen Interactions/physiology
• Humans
• Necroptosis/physiology
• Pyroptosis/physiology
• Regulated Cell Death/physiology
• Signal Transduction/physiology

• R01 AI040646 NIAID NIH HHS
• R01 AI044828 NIAID NIH HHS
• R35 CA231620 NCI NIH HHS
• R37 AI044828 NIAID NIH HHS
• HHS | NIH | NCI | Basic Research Laboratory (BRL)
• HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (DMID)
• HHS | NIH | National Cancer Institute (NCI)
• American Lebanese Syrian Associated Charities (ALSAC)

• RLR signaling pathway
• TLR signaling pathway
• apoptosis
• cGAS-STING pathway
• caspase activity regulation
• caspase cleavage
• cell death
• necroptosis
• pyroptosis
• virus

• Animals
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/metabolism
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Disease Progression
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• Imidazoles/administration & dosage
• Imidazoles/pharmacology
• Mice
• Naphthoquinones/administration & dosage
• Naphthoquinones/pharmacology
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Precision Medicine
• Survivin/antagonists & inhibitors
• Survivin/genetics
• Survivin/metabolism
• Transplantation, Heterologous
• Up-Regulation/drug effects

An infectious etiology for a number of cancers has been entertained for over 100 years and modern studies have confirmed that a number of viruses are linked to cancer induction. While a large number of viruses have been demonstrated in a number of types of cancers, most such findings have been dismissed in the past as opportunistic infections, especially with persistent viruses with high rates of infectivity of the world’s populations. More recent studies have clearly shown that while not definitely causing these cancers, these viruses appear capable of affecting the biology of these tumors in such a way as to make them more aggressive and more resistant to conventional treatments. The term oncomodulatory viruses has been used to describe this phenomenon. A number of recent studies have shown a growing number of ways these oncomodulatory viruses can alter the pathology of these tumors by affecting cell-signaling, cell metabolism, apoptosis mechanisms, cell-cell communication, inflammation, antitumor immunity suppression, and angiogenesis. We are also learning that much of the behavior of tumors depends on cancer stem cells and stromal cells within the tumor microenvironment, which participate in extensive, dynamic crosstalk known to affect tumor behavior. Cancer stem cells have been found to be particularly susceptible to infection by human cytomegalovirus. In a number of studies, it has been shown that while only a select number of cells are actually infected with the virus, numerous viral proteins are released into cancer and stromal cells in the microenvironment and these viral proteins are known to affect tumor behavior and aggressiveness.

• Cytomegalovirus
• Microenvironment
• Oncomodulation
• Viral proteins

• EBV
• KSHV
• caspases
• immune evasion
• lytic replication

• KSHV
• caspases
• type I interferon

• USP7
• human herpesvirus 8
• latency
• lytic replication
• viral interferon regulatory factors

Viruses must exploit the cellular biosynthetic machinery and evade cellular defense systems to complete their life cycles. Due to their crucial roles in cellular bioenergetics, apoptosis, innate immunity and redox balance, mitochondria are important functional targets of many viruses, including tumor viruses. The present review describes the interactions between mitochondria and proteins coded by the human tumor viruses human T-cell leukemia virus type 1, Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, human hepatitis viruses B and C, and human papillomavirus, and highlights how these interactions contribute to viral replication, persistence and transformation.

• EBV
• HBV
• HCV
• HPV
• HTLV-1
• KSHV
• Mitochondria

• Akt
• Apoptosis
• Cell cycle
• IFN
• IRF
• KSHV
• MAPK
• NF-κB
• Notch
• Signal transduction pathway
• Viral microRNA
• Viral noncoding RNA
• Wnt/β-catenin
• p53

The family of double-stranded DNA (dsDNA) Malacoherpesviridae includes viruses able to infect marine mollusks and detrimental for worldwide aquaculture production. Due to fast-occurring mortality and a lack of permissive cell lines, the available data on the few known Malacoherpesviridae provide only partial support for the study of molecular virus features, life cycle, and evolutionary history. Following thorough data mining of bivalve and gastropod RNA-seq experiments, we used more than five million Malacoherpesviridae reads to improve the annotation of viral genomes and to characterize viral InDels, nucleotide stretches, and SNPs. Both genome and protein domain analyses confirmed the evolutionary diversification and gene uniqueness of known Malacoherpesviridae. However, the presence of Malacoherpesviridae-like sequences integrated within genomes of phylogenetically distant invertebrates indicates broad diffusion of these viruses and indicates the need for confirmatory investigations. The manifest co-occurrence of OsHV-1 genotype variants in single RNA-seq samples of Crassostrea gigas provide further support for the Malacoherpesviridae diversification. In addition to simple sequence motifs inter-punctuating viral ORFs, recombination-inducing sequences were found to be enriched in the OsHV-1 and AbHV1-AUS genomes. Finally, the highly correlated expression of most viral ORFs in multiple oyster samples is consistent with the burst of viral proteins during the lytic phase.

• Herpesvirales
• Malacoherpesviridae
• OsHV-1
• RNA-seq
• bivalve
• viromes

• KSHV
• antiviral mechanisms
• cellular homologues
• rhadinovirus
• viral interferon regulatory factor

• Biodistribution
• exosomes
• melanoma
• proliferation
• uptake

VDAC3 is the least known isoform of the mammalian voltage-dependent anion selective channels of the outer mitochondrial membrane. It has been recently shown that cysteine residues of VDAC3 are found over-oxidized. The VDAC3 cysteine over-oxidation was associated with the oxidizing environment and the abundance of reactive oxygen species (ROS) in the intermembrane space. In this work, we have examined the role of VDAC3 in general pathogenic mechanisms at the basis of mitochondrial dysfunction and involving the mitochondrial quality control. Many of the diseases reported here, including cancer and viral infections, are often associated with significant changes in the intracellular redox state. In this sense, VDAC3 bearing oxidative modifications could become marker of the oxidative load in the mitochondria and part of the ROS signaling pathway.

• VDAC3
• aging
• cancer
• cysteine over-oxidation
• mitochondria quality control
• mitochondrial dysfunction
• mitophagy

• Acquired immune deficiency syndrome
• Castleman disease
• Human herpesvirus type-8
• Interleukin-6
• Kaposi sarcoma-associated herpesvirus
• TAFRO syndrome

• Castleman Disease/pathology
• Castleman Disease/virology
• HIV
• Herpesvirus 8, Human
• Humans

• Z01 BC011070-01 Intramural NIH HHS
• ZIA BC011070-08 Intramural NIH HHS

• Antioxidant response
• Apoptosis signaling kinase 1
• ER stress
• Heat shock factor 1
• Inflammatory response
• Proteotoxic stress

• Apoptosis/drug effects
• Cell Survival/drug effects
• Endoplasmic Reticulum Stress/drug effects
• Humans
• MAP Kinase Signaling System/drug effects
• NF-E2-Related Factor 2/metabolism
• NF-kappa B/metabolism
• Neoplasms/pathology
• Neoplasms/therapy
• Oxidative Stress/drug effects
• Oxidative Stress/physiology
• Photochemotherapy/methods
• Photosensitizing Agents/therapeutic use
• Reactive Oxygen Species/metabolism

• R01 AI050875 NIAID NIH HHS

• Cancer
• Diagnosis
• Splice variants
• Survivin
• p53

We summarized the most recent findings on the role of autophagy in antiviral immune response. We described how viruses have developed strategies to subvert the autophagic process. A particular attention has been given to Epstein-Barr and Kaposi's sarcoma associated Herpesvirus, viruses studied for many years in our laboratory. These two viruses belong to γ-Herpesvirus subfamily and are associated with several human cancers. Besides the effects on the immune response, we have described how autophagy subversion by viruses may also concur to the enhancement of their replication and to viral tumorigenesis.

Despite much work, safe and effective approaches to attack and deplete the long-lived reservoir of cells latently infected with HIV-1 remain an elusive goal. Patients infected with HIV-1 treated with cytotoxic agents or bone marrow transplantation can experience decreases in the reservoir of HIV-1 latently infected cells. Other viruses capable of long-term latency, such as herpesviruses, can sense host cell apoptosis and respond by initiating replication. These observations suggest that other viruses capable of long-term latency, like HIV-1, might also sense when its host cell is about to undergo apoptosis and respond by initiating replication.

Pro-monocytic (U1) and lymphoid (ACH-2) HIV-1 persistently infected cell lines were treated with cytotoxic drugs – doxorubicin, etoposide, fludarabine phosphate, or vincristine – and activation of latent HIV-1 was evaluated using assays for HIV-1 RNA and p24 production. Both cell lines showed dose-dependent increases in apoptosis and associated HIV-1 activation following exposure to the cytotoxic agents. Pretreatment of the cells with the pan-caspase inhibitor Z-VAD-FMK prior to exposure to the cytotoxic agents inhibited apoptosis and viral activation. Direct exposure of the latently infected cell lines to activated caspases also induced viral replication. HIV-1 virions produced in association with host cell apoptosis were infectious.

The results indicate that latent HIV-1 can sense when its host cell is undergoing apoptosis and responds by completing its replication cycle. The results may help explain why patients treated with cytotoxic regimens for bone marrow transplantation showed reductions in the reservoir of latently infected cells. The results also suggest that the mechanisms that HIV-1 uses to sense and respond to host cell apoptosis signals may represent helpful new targets for approaches to attack and deplete the long-lived reservoir of cells latently infected with HIV-1.

Kaposi’s sarcoma-associated herpesvirus (KSHV) primarily persists as a latent episome in infected cells. During latent infection, only a limited number of viral genes are expressed that help to maintain the viral episome and prevent lytic reactivation. The latent KSHV genome persists as a highly ordered chromatin structure with bivalent chromatin marks at the promoter-regulatory region of the major immediate-early gene promoter. Various stimuli can induce chromatin modifications to an active euchromatic epigenetic mark, leading to the expression of genes required for the transition from the latent to the lytic phase of KSHV life cycle. Enhanced replication and transcription activator (RTA) gene expression triggers a cascade of events, resulting in the modulation of various cellular pathways to support viral DNA synthesis. RTA also binds to the origin of lytic DNA replication to recruit viral, as well as cellular, proteins for the initiation of the lytic DNA replication of KSHV. In this review we will discuss some of the pivotal genetic and epigenetic factors that control KSHV reactivation from the transcriptionally restricted latent program.

• Animals
• Apoptosis
• Autophagy
• Host-Pathogen Interactions
• Humans
• Interferon Regulatory Factors
• Interferons
• Mice
• NF-kappa B
• Signal Transduction
• Viral Proteins
• Virus Diseases

• CA161436 NCI NIH HHS
• R01 HL110609 NHLBI NIH HHS
• R01 CA140964 NCI NIH HHS
• AI073099 NIAID NIH HHS
• R01 CA082057 NCI NIH HHS
• CA31363 NCI NIH HHS
• HL110609 NHLBI NIH HHS
• R01 AI073099 NIAID NIH HHS
• R01 CA031363 NCI NIH HHS
• CA180779 NCI NIH HHS
• R01 DE023926 NIDCR NIH HHS
• P01 CA180779 NCI NIH HHS
• R21 CA161436 NCI NIH HHS
• R01 CA115284 NCI NIH HHS
• CA082057 NCI NIH HHS
• CA115284 NCI NIH HHS
• AI105809 NIAID NIH HHS
• CA140964 NCI NIH HHS

• Crassostrea gigas
• In situ hybridization
• Ostreid herpesvirus type 1
• Pacific oyster
• Viral infection
• mRNA

• Chronic allograft injury
• gene therapy
• ischemia/reperfusion injury
• kidney transplantation
• survivin

• Herpesviridae Infections/metabolism
• Herpesviridae Infections/virology
• Herpesvirus 8, Human/pathogenicity
• Herpesvirus 8, Human/physiology
• Host-Pathogen Interactions
• Humans
• Molecular Biology
• Virus Replication

• R56 AI098501 NIAID NIH HHS
• P30 CA006973 NCI NIH HHS
• R01 CA076445 NCI NIH HHS
• R01 AI106393 NIAID NIH HHS
• R21 AI099655 NIAID NIH HHS
• R21 CA171937 NCI NIH HHS

Despite numerous comparative mitochondrial genomics studies revealing that animal mitochondrial genomes are highly conserved in terms of gene content, supplementary genes are sometimes found, often arising from gene duplication. Mitochondrial ORFans (ORFs having no detectable homology and unknown function) were found in bivalve molluscs with Doubly Uniparental Inheritance (DUI) of mitochondria. In DUI animals, two mitochondrial lineages are present: one transmitted through females (F-type) and the other through males (M-type), each showing a specific and conserved ORF. The analysis of 34 mitochondrial major Unassigned Regions of Musculista senhousia F- and M-mtDNA allowed us to verify the presence of novel mitochondrial ORFs in this species and to compare them with ORFs from other species with ascertained DUI, with other bivalves and with animals showing new mitochondrial elements. Overall, 17 ORFans from nine species were analyzed for structure and function. Many clues suggest that the analyzed ORFans arose from endogenization of viral genes. The co-option of such novel genes by viral hosts may have determined some evolutionary aspects of host life cycle, possibly involving mitochondria. The structure similarity of DUI ORFans within evolutionary lineages may also indicate that they originated from independent events. If these novel ORFs are in some way linked to DUI establishment, a multiple origin of DUI has to be considered. These putative proteins may have a role in the maintenance of sperm mitochondria during embryo development, possibly masking them from the degradation processes that normally affect sperm mitochondria in species with strictly maternal inheritance.

• Doubly Uniparental Inheritance of mitochondria
• endogenous virus
• mitochondrial ORFans
• mitochondrial inheritance

New treatment modalities are needed for the treatment of cancers of the head and neck region (HNSCC). Survivin is important for the survival and proliferation of tumor cells and may therefore provide a target for immunotherapy. Here we focused on the ex vivo presence and in vitro induction of survivin specific T cells.

Tetramer staining and ELIspot assays were used to document the presence of survivin specific T cells in patient derived material, and to monitor the presence and persistence of survivin specific T cells after repeated in vitro stimulation with autologous dendritic cells.

Ex vivo analysis showed the presence of survivin-specific T cells in the peripheral blood (by tetramer analysis) and in the draining lymph node (by ELIspot analysis) in a HNSCC and a locally advanced breast cancer patient respectively. However, we were unable to maintain isolated survivin specific T cells for prolonged periods of time. For the in vitro generation of survivin specific T cells, monocyte derived DC were electroporated with mRNA encoding full length survivin or a survivin mini-gene together with either IL21 or IL12 mRNA. Western blotting and immunohistochemical staining of dendritic cell cytospin preparations confirmed translation of the full length survivin protein. After repeated stimulation we observed an increase, followed by a decrease, of the number of survivin specific T cells. FACS sorted or limiting dilution cloned survivin specific T cells could not be maintained on feeder mix for prolonged periods of time. Protein expression analysis subsequently showed that activated, but not resting T cells contain survivin protein.

Here we have shown that survivin specific T cells can be detected ex vivo in patient derived material. Furthermore, survivin specific T cells can be induced in vitro using autologous dendritic cells with enforced expression of survivin and cytokines. However, we were unable to maintain enriched or cloned survivin specific T cells for prolonged periods of time. Endogenous expression of survivin in activated T cells and subsequent fratricide killing might explain our in vitro observations. We therefore conclude that survivin, although it is a universal tumor antigen, might not be the ideal target for immunotherapeutic strategies for the treatment of cancer of the head and neck.

• Gammaherpesvirinae/immunology
• Gammaherpesvirinae/physiology
• Humans
• Immune Evasion
• Immunity, Innate
• Virus Latency

• R01 CA134241 NCI NIH HHS
• R01 DE021445 NIDCR NIH HHS

• DNA replication
• DNA synthesis
• KSHV
• Kaposi's sarcoma
• O-GlcNAc

Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of host cells. For HHV-8, viral interferon regulatory factor-1 (vIRF-1) contributes to this process in part via inhibitory interactions with BH3-only protein (BOP) Bim, recently identified as an interaction partner of vIRF-1. Here we recognize that the Bim-binding domain (BBD) of vIRF-1 resembles a region (BH3-B) of Bid, another BOP, which interacts intramolecularly with the functional BH3 domain of Bid to inhibit it pro-apoptotic activity. Indeed, vIRF-1 was found to target Bid in addition to Bim and to interact, via its BBD region, with the BH3 domain of each. In functional assays, BBD could substitute for BH3-B in the context of Bid, to suppress Bid-induced apoptosis in a BH3-binding-dependent manner, and vIRF-1 was able to protect transfected cells from apoptosis induced by Bid. While vIRF-1 can mediate nuclear sequestration of Bim, this was not the case for Bid, and inhibition of Bid and Bim by vIRF-1 could occur independently of nuclear localization of the viral protein. Consistent with this finding, direct BBD-dependent inactivation by vIRF-1 of Bid-induced mitochondrial permeabilization was demonstrable in vitro and isolated BBD sequences were also active in this assay. In addition to Bim and Bid BH3 domains, BH3s of BOPs Bik, Bmf, Hrk, and Noxa also were found to bind BBD, while those of both pro- and anti-apoptotic multi-BH domain Bcl-2 proteins were not. Finally, the significance of Bid to virus replication was demonstrated via Bid-depletion in HHV-8 infected cells, which enhanced virus production. Together, our data demonstrate and characterize BH3 targeting and associated inhibition of BOP pro-apoptotic activity by vIRF-1 via Bid BH3-B mimicry, identifying a novel mechanism of viral evasion from host cell defenses.

Viruses possess mechanisms of subverting host cell defenses against infection and virus replication; these mechanisms are essential to the virus life cycle. Here, we identify and characterize a novel mechanism of HHV-8 mediated inhibition of virus-induced programmed cell death (apoptosis). This function is specified by viral interferon regulator factor homologue vIRF-1, which binds to and directly inhibits pro-death activities of so-called BH3-only proteins (BOPs), induced and activated by stress signals such as those occurring in infected cells. The BH3 domains of BOPs mediate their pro-apoptotic functions, and it is these domains that are targeted by vIRF-1, via a region resembling a BH3-interacting and -inhibitory domain, termed BH3-B, present in one of the vIRF-1 targeted BOPs, Bid. The targeted BOP BH3 domains share characteristic and conserved features. As shown previously for Bim, depletion of Bid leads to enhanced HHV-8 productive replication, demonstrating that Bid, also, is a biologically significant negative regulator of virus replication and suggesting that its control by vIRF-1 is of functional importance. To our knowledge, this is the first report of viral targeting and inhibition of BOP activity via Bid BH3-B mimicry; our studies therefore expand the known mechanisms of viral evasion from antiviral defenses of the host.