Sabrina Schreiner

Sabrina Schreiner
Technische Universität München | TUM · Institute of Virology

PhD

About

51
Publications
6,468
Reads
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1,116
Citations
Additional affiliations
August 2010 - December 2014
Heinrich Pette Institute – Leibniz Institute for Experimental Virology
Position
  • Senior Researcher

Publications

Publications (51)
Article
Full-text available
Promyelocytic leukemia nuclear bodies (PML-NBs) were considered to maintain antiviral capacity, as these spherical complexes are antagonized by viruses. Actual work provides evidence, that PML-NB-associated factors might also be beneficial for distinct viral processes indicating why genomes and replication centers of nuclear replicating viruses are...
Article
Full-text available
Over the past decades, studies on the biology of human adenoviruses (HAdVs) mainly focused on the HAdV prototype species C type 5 (HAdV-C5) and revealed fundamental molecular insights into mechanisms of viral replication and viral cell transformation. Recently, other HAdV species are gaining more and more attention in the field. Reports on large E1...
Article
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Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that cannot be targeted by available antivirals. Interferons can diminish HBV cccDNA via APOBEC3-mediated deamination. Here, we show that overexpression of APOBEC3A alone is not sufficient to reduce HBV cccDNA that requires addi...
Article
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BACKGROUNG & AIMS The existence of different subtypes of pancreatic ductal adenocarcinoma (PDAC) and their correlation with patient outcome have shifted the emphasis on patient classification for better decision-making algorithms and personalized therapy. The contribution of mechanisms regulating the cancer stem cell (CSC) population in different s...
Article
PML nuclear bodies are matrix-bound nuclear structures with a variety of functions in human cells. These nuclear domains are interferon regulated and play an essential role during virus infections involving accumulation of SUMO-dependent host and viral factors. PML-NBs are targeted and subsequently manipulated by adenoviral regulatory proteins, ill...
Article
Background & Aims Selective elimination of virus-infected hepatocytes occurs through virus-specific CD8 T-cells recognizing peptide-loaded MHC molecules. Here, we report that virus-infected hepatocytes are also selectively eliminated through a cell-autonomous mechanism. Methods We generated recombinant adenoviruses and genetically modified mouse m...
Article
Full-text available
Human adenoviruses (HAdV) are associated with clinical symptoms such as gastroenteritis, keratoconjunctivitis, pneumonia, hepatitis, and encephalitis. In the absence of protective immunity, as in allogeneic bone marrow transplant patients, HAdV infections can become lethal. Alarmingly, various outbreaks of highly pathogenic, pneumotropic HAdV types...
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PML nuclear bodies (PML-NBs) are implicated in general antiviral defense based on recruiting host restriction factors; however, it is not understood so far why viruses would establish viral replication centers (RCs) juxtaposed to such “antiviral” compartments. To understand this enigma, we investigate the cross talk between PML-NB components and vi...
Article
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Chronic hepatitis B is one of the world’s unconquered diseases with more than 240 million infected subjects at risk of developing liver disease and hepatocellular carcinoma. Hepatitis B virus reverse transcribes pre-genomic RNA to relaxed circular DNA (rcDNA) that comprises the infectious particle. To establish infection of a naïve target cell, the...
Article
The cellular protein SPOC1 (survival time-associated PHD [plant homeodomain] finger protein in ovarian cancer 1) acts as a regulator of chromatin structure and the DNA damage response. It binds H3K4me2/3-containing chromatin and promotes DNA condensation by recruiting corepressors such as KAP-1 and H3K9 methyltransferases. Previous studies identifi...
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HAdV E1B-55K is a multifunctional regulator of productive viral replication and oncogenic transformation in non-permissive mammalian cells. These functions depend on E1B-55K's posttranslational modification with the SUMO protein and its binding to HAdV E4orf6. Both early viral proteins recruit specific host factors to form an E3 Ubiquitin ligase co...
Article
Human Adenoviruses (HAdV) are non-enveloped containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear-pore-complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was...
Article
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Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large ext...
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Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infect...
Article
Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC), a rare but aggressive skin cancer. The virus is highly prevalent: 60-80% of adults are seropositive; however, cells permissive for MCPyV infection are unknown. Consequently, very little information about the MCPyV life cycle is available. Until recently, MCPyV replicat...
Article
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Human adenovirus E1A proteins have long been known as the central regulators of virus infection as well as the major source of adenovirus oncogenic potential. Not only do they activate expression of other early viral genes, they make viral replication possible in terminally differentiated cells, at least in part, by binding to the Rb tumor suppress...
Article
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The human adenovirus E4orf6/E1B55K E3 ubiquitin ligase is well known to promote viral replication by degrading an increasing number of cellular proteins that inhibit the efficient production of viral progeny. We report here a new function of the Ad5 viral ligase complex that, although at lower levels, mimics effects of E1A products on E2F transcrip...
Article
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Importance: Here we describe a novel cellular restriction factor for Human Adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin formation and cellular SWI/SNF chromatin remodeling play a key role in HAdV transcriptional regulation (1-4). We observed that the cellular chromatin-associa...
Article
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Human adenoviruses (HAdV) are used as a model system to investigate tumorigenic processes in mammalian cells where the viral oncoproteins E1A and E1B-55K are absolutely required for oncogenic transformation, because they simultaneously accelerate cell cycle progression and inhibit tumor suppressor proteins such as p53, although the underlying mecha...
Article
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Posttranslational modifications (PTMs) of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub) and small ubiquitin-like modifier (SUMO) moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became appa...
Article
Full-text available
Although modulation of the cellular tumor-suppressor p53 is considered to have the major role in E1A/E1B-55K-mediated tumorigenesis, other promyelocytic leukemia nuclear body (PML-NB)/PML oncogenic domain (POD)-associated factors including SUMO, Mre11, Daxx, as well as the integrity of these nuclear bodies contribute to the transformation process....
Article
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We have previously demonstrated that acquisition of intricate patterns of activating (H3K4me3, H3K9/K14ac) and repressive (H3K27me3) histone modifications is a hallmark of KSHV latency establishment. The precise molecular mechanisms that shape the latent histone modification landscape, however, remain unknown. Promyelocytic leukemia nuclear bodies...
Article
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The adenovirus type 5 (Ad5) E1B 55kDa and E4 Orf6 proteins assemble a Cullin 5-E3 ubiquitin (Ub) ligase that targets, among other cellular proteins, p53 and the Mre11-Rad50-Nbs1 (MRN) complex for degradation. The latter is also inhibited by the E4 Orf3 protein, which promotes the recruitment of the Mre11 protein into specific nuclear sites to promo...
Article
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Unlabelled: Promyelocytic leukemia nuclear bodies (PML-NBs) are nuclear structures that accumulate intrinsic host factors to restrict viral infections. To ensure viral replication, these must be limited by expression of viral early regulatory proteins that functionally inhibit PML-NB-associated antiviral effects. To benefit from the activating cap...
Article
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Little is known about immediate phases after viral infection and how an incoming viral genome complex counteracts host cell defenses, before the start of viral gene expression. Adenovirus (Ad) serves as an ideal model, since entry and onset of gene expression are rapid and highly efficient, and mechanisms used 24-48 hours post infection to countera...
Article
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PML nuclear bodies and their associated functions are part of an intrinsic cellular mechanism aimed to maintain transcriptional control over viral gene expression and prevent replication of invading viruses. To overcome these barriers many viruses express early non-structural, multi-functional proteins to support the viral replication cycle or modu...
Article
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The E4orf6 protein of serotypes representing all human adenovirus species form Cullin-based E3 ubiquitin ligase complexes that facilitate virus infection by inducing degradation of cellular proteins that impede efficient viral replication. This complex also includes the viral E1B55K product believed to bind and introduce substrates for ubiquitinati...
Article
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Death domain-associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruit...
Article
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PML-NBs, also called ND10 are matrix-bound nuclear structures that have been implicated in a variety of functions, including DNA repair, transcriptional regulation, protein degradation, and tumor suppression. These domains are also known for their potential to mediate an intracellular defense mechanism against many virus types. This is likely why t...
Article
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Since the discovery of post-translational modification (PTM) by the small ubiquitin-related modifiers (SUMOs), a multitude of proteins have been described to be reversibly modified, resulting in the alteration of several cellular pathways. Interestingly, various pathogens gain access to this modification system, although the molecular mechanisms an...
Article
Full-text available
Human adenovirus type 5 (HAdV5) E4orf6 (early region 4 open reading frame 6 protein) is a multifunctional early viral protein promoting efficient replication and progeny production. E4orf6 complexes with E1B-55K to assemble cellular proteins into a functional E3 ubiquitin ligase complex that not only mediates proteasomal degradation of host cell su...
Data
The supporting information contains a list of all antibodies used in this study (Protocol S1), a detailed protocol for the co-immunoprecipitation assays (Protocol S2) and additional references used in Figures S1, S2, S3, S4, S5, S6, S7. (DOC)
Data
Microinjection of recombinant protein VI-M1 displaces Daxx from PML bodies to the cytoplasm. U2OS cells were cotransfected with Daxx-mCherry (left panel) and PML-GFP (middle panel) expression plasmids (superimposed signal on the right) and cultivated at 37°C on a heated stage in CO2 stabilized medium attached to a SP5 confocal microscope equipped w...
Data
Quantification of viral genomes in fractionated cells. (A) U2OS cells were synchronously infected with replication competent HH-Ad5-wt or HH-Ad5-M1 virus at 200, 10 or 1 physical particles per cell (pp/cell) as virus input –A-. Forty five min after infection, the cytoplasmic –B- and nuclear –C- fractions were separated using nucleo-cytoplasmic frac...
Data
PML-NB association of protein VI requires the amphipathic helix. To identify the domain of protein VI required for PML-NB association, several mRFP tagged constructs for protein VI were transfected into U2OS cells and stained for association with endogenous PML. The mRFP signal is shown in the left column. An overlay of the mRFP protein VI signal (...
Data
Protein VI mediates adenovirus transcriptional activation of all Ad promoters. Subconfluent H1299 cells were transfected with luciferase reporter plasmids encoding for the E1A-, E1B-, pIX-, E2early-, E2late-, E3-, E4-promoters and the major late promoter (MLP) and effector plasmids expressing VI-wt, VI-M1. Fortyeight hours after transfection, sampl...
Data
Protein VI targets Nedd4 ligases to PML-NBs via the PPxY motif. U2OS cells were transfected with expression constructs for GFP-tagged Nedd4 ligases and RFP-tagged expression constructs for protein VI-wt or VI-M1 and stained for endogenous PML, as indicted to the left of each row. From top to bottom; Nedd4.1-GFP was cotransfected with VI-wt (a) or V...
Data
Transfected viral capsid proteins partially displace Daxx from PML bodies. H1299 (a–c) and U2OS (d–f) cells were transfected with either empty control plasmid (a, d) or mRFP-tagged VI-wt (b, e) or mRFP-tagged VI-M1 (c) or with an HA-tagged expression vector for the pp71 tegument protein of the human cytomegalovirus (f, all first columns). Transfect...
Data
Protein VI-wt activates the CMV promoter of E1-deleted Ad vector particles with M1 mutated protein VI. U2OS cells were transduced with 1 physical particle per cell (pp/cell) of E1-deleted viral vector BxAd5-VI-M1-mCherry (expressing mCherry under CMV promoter control and M1 mutated protein VI) and different amounts of viral vector BxAd5-VI-wt-GFP (...
Data
Microinjection of recombinant protein VI-delta54 transiently displaces Daxx from PML bodies but fails to export Daxx to the cytoplasm. U2OS cells were cotransfected with Daxx-mCherry (left panel) and PML-GFP (middle panel) expression plasmids (superimposed signal on the right) and cultivated at 37°C on a heated stage in CO2 stabilized medium attach...
Data
Construction of virus mutant HH-Ad5-VI-M1 by site directed mutagenesis. (A) For the construction of the replication competent virus mutant HH-Ad5-VI-M1, the Ad5 wild type genome in HH-Ad5-VI-wt [H5pg4100; 67] was inserted into the PacI site of the bacterial cloning vector pPG-S2 [67]. It lacks nucleotides (nt) 28593 to 30471 (encompassing most of E...
Data
Microinjection of recombinant protein VI-wt displaces Daxx from PML bodies to the cytoplasm. U2OS cells were cotransfected with Daxx-mCherry (left panel) and PML-GFP (middle panel) expression plasmids (superimposed signal on the right) and cultivated at 37°C on a heated stage in CO2 stabilized medium attached to a SP5 confocal microscope equipped w...
Article
Full-text available
Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents viral gene expression through t...
Article
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Eukaryotic cells orchestrate constant synthesis and degradation of intracellular components, including soluble proteins and organelles. The two major intracellular degradation pathways are the ubiquitin/proteasome system and autophagy. Whereas ubiquitin/proteasome system is involved in rapid degradation of proteins, autophagy selectively removes pr...
Article
Full-text available
Since posttranslational modification (PTM) by the small ubiquitin-related modifiers (SUMOs) was discovered over a decade ago, a huge number of cellular proteins have been found to be reversibly modified, resulting in alteration of differential cellular pathways. Although the molecular consequences of SUMO attachment are difficult to predict, the un...
Article
Full-text available
Early region 1B 55K (E1B-55K) from adenovirus type 5 (Ad5) is a multifunctional regulator of lytic infection and contributes in vitro to complete cell transformation of primary rodent cells in combination with Ad5 E1A. Inhibition of p53 activated transcription plays a key role in processes by which E1B-55K executes its oncogenic potential. Neverthe...
Article
Full-text available
The E1B-55K product from human adenovirus is a substrate of the small ubiquitin-related modifier (SUMO)-conjugation system. SUMOylation of E1B-55K is required to transform primary mammalian cells in cooperation with adenovirus E1A and to repress p53 tumour suppressor functions. The biochemical consequences of SUMO1 conjugation of 55K have so far re...
Article
Full-text available
The death-associated protein Daxx found in PML (promyelocytic leukemia protein) nuclear bodies (PML-NBs) is involved in transcriptional regulation and cellular intrinsic antiviral resistence against incoming viruses. We found that knockdown of Daxx in a nontransformed human hepatocyte cell line using RNA interference (RNAi) techniques results in si...
Article
Full-text available
The adenovirus type 5 (Ad5) early region 1B 55-kDa (E1B-55K) protein is a multifunctional regulator of cell-cycle-independent virus replication that participates in many processes required for maximal virus production. As part of a study of E1B-55K function, we generated the Ad5 mutant H5pm4133, carrying stop codons after the second and seventh cod...

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