Bhupesh Prusty

Bhupesh Prusty
University of Wuerzburg | JMU · Institute for Virology and Immune Biology

PhD

About

132
Publications
14,985
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Introduction
Bhupesh Prusty currently works at the Institute for Virology and Immunobiology, University of Wuerzburg. Bhupesh does research in Microbiology and Virology. His current research focuses on ciHHV-6 reactivation and its clinical consequences.
Additional affiliations
July 2018 - present
Institute for Virology and Immunobiology, Universität Würzburg
Position
  • Senior Researcher
January 2009 - June 2018
University of Wuerzburg
Position
  • Group Leader
January 2006 - December 2008
German Cancer Research Center
Position
  • PostDoc Position

Publications

Publications (132)
Article
Full-text available
Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation1,2. A long appreciated, yet undefined relationship exists between the lytic–latent switch and viral non-coding RNAs3,4. Here we identify viral microRNA (miRNA)-mediated inhibition of host miRNA processing as a cell...
Article
Full-text available
Viruses play a key role in explaining the pathogenesis of various autoimmune disorders, whose underlying principle is defined by the activation of autoreactive T-cells. In many cases, T-cells escape self-tolerance due to the failure in encountering certain MHC-I self-peptide complexes at substantial levels, whose peptides remain invisible from the...
Article
Full-text available
In response to infections, human immune cells release extracellular vesicles (EVs) that carry a situationally adapted cocktail of proteins and nucleic acids, including microRNAs (miRNAs), to coordinate the immune response. In this study, we identified hsa-miR-21-5p and hsa-miR-24-3p as the most common miRNAs in exosomes released by human monocytes...
Preprint
For decades, human cytomegalovirus (HCMV) was thought to express ≈200 viral proteins during lytic infection. In recent years, systems biology approaches uncovered hundreds of additional viral gene products and suggested thousands of viral sites of transcription initiation. Despite all available data, the molecular mechanisms of HCMV gene regulation...
Preprint
Full-text available
Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation thereof 1,2. A long appreciated, yet elusively defined relationship exists between the lytic-latent switch and viral non-coding RNAs 3,4. Here, we identify miRNA-mediated inhibition of miRNA processing as a novel c...
Article
Full-text available
A sulfasalazine‐induced DRESS (Drug Reactivation with Eosinophilia and Systemic Symptoms) was complicated by a Crohn's‐like colitis. We demonstrated HHV‐6 reactivation with presence of HHV‐6 DNA and small noncoding RNA in colonic lesions. This observation confirms the major role of HHV‐6 reactivation in DRESS manifestations and the importance of lo...
Article
Background Distinctions between HHV-6 primary infection in seronegative patients and HHV-6 reactivation in seropositive patients remains largely undescribed in pediatric liver transplant (LT) recipients. Methods We implemented pretransplant serology testing of HHV-6 in a large pediatric hospital and retrospectively assessed the incidence, manifest...
Article
Full-text available
The HSV-1 virion host shutoff ( vhs ) protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in vhs activity, as well as virus-induced global loss of host transcriptional activity, during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA leve...
Article
Full-text available
Objectives- To evaluate HHV-6 and PVB19 infection using PCR and IFA in the myocardium of pediatric patients with dilated cardiomyopathy (DCM) and the impact of viral persistence in the cardiac allograft after heart transplantation (HT). Methods- Multiplex droplet digital PCR was used to analyze the prevalence of viral sequences in myocardial sample...
Preprint
Full-text available
Herpes simplex virus 1 (HSV-1) installs a profound host shut-off during lytic infection. The virion host shut-off ( vhs ) protein plays a key role in this process by efficiently cleaving both host and viral mRNAs in a translation-initiation-dependent manner. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in transc...
Article
Full-text available
Background: Cytomegalovirus (CMV) infection remains a significant cause of morbidity among pediatric heart transplant (HTx) recipients. We explored the implications of CMV infection on post-transplant outcomes among CMV risk stratified pediatric HTx recipients receiving 6M valganciclovir (VGC) prophylaxis. Methods: Retrospective review of pediatri...
Article
HHV‐6A can be inherited and chromosomally integrated (iciHHV‐6A), and donor to recipient transmission has been reported in solid‐organ transplantation. However, when HHV‐6A reactivation happens after transplantation, the source of HHV‐6A is often not evident and its pathogenicity remains unclear. Here, we present an exhaustive case of donor‐to‐reci...
Article
Full-text available
The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including al...
Article
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disorder with many possible triggers. Human herpesvirus (HHV)-6 and HHV-7 are two infectious triggers for which evidence has been growing. To understand possible causative role of HHV-6 in ME/CFS, metabolic and antiviral phenotypes of U2-OS cells were studied with and w...
Article
Full-text available
Combining integrative genomics and systems biology approaches has revealed new and conserved features in the genome of human herpesvirus 6.
Article
Full-text available
Infection by viruses, including herpes simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes. However, the underlying mechanisms remain unclear. Here, we demonstrate that the HSV-1 immediate early protein ICP27 induces DoTT by directly binding to th...
Article
Full-text available
Obligate intracellular pathogenic Chlamydia trachomatis express several serine proteases whose roles in chlamydial development and pathogenicity are not completely understood. The chlamydial protease CPAF is expressed during the replicative phase of the chlamydial developmental cycle and is secreted into the lumen of the Chlamydia-containing vacuol...
Article
Background: Active infections of human herpesvirus 6B (HHV-6B) are frequent in immunocompromised recipients after transplantation. Nevertheless, they need to be distinguished from latent inherited chromosomally integrated genomes (iciHHV-6) present in about 1% of the population, to avoid unnecessary administration of toxic antivirals. Methods: A...
Article
Full-text available
Background/objectives: With mucocutaneous candidiasis being highly prevalent in HIV patients, the emergence of fluconazole-resistant Candida species forms a major challenge in treating and eradicating these infections. The objective of this study was to establish the antifungal activity of K21, a membrane-rupturing antimicrobial compound derived fr...
Conference Paper
Objectives: To study the relation between asymptomatic CMV infection in the first year after transplant and subsequent rejection, CAV and graft loss in pediatric HTx recipients in the era of valganciclovir prophylaxis. Methods: Retrospective study was done of 97 first-time pediatric HTx recipients between 1.1.2010 and 10.30.2016. Asymptomatic CMV i...
Conference Paper
Objectives- To evaluate HHV-6 and PVB19 infection using PCR and IFA in the myocardium of pediatric patients with dilated cardiomyopathy (DCM) and the prognostic implications of viral presence. Methods- Multiplex droplet digital PCR was used to analyze the prevalence of viral sequences in myocardial samples from 48 pediatric DCM patients and 10 con...
Preprint
Full-text available
Since the genome of herpes simplex virus 1 (HSV-1) was first sequenced more than 30 years ago, its predicted 80 genes have been intensively studied. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identified a total of 201 viral t...
Article
Purpose To study the relation between the presence and absence of asymptomatic CMV infection in the first year after heart transplant (HT) and subsequent rejection, cardiac allograft vasculopathy (CAV) and graft loss in the era of valganciclovir prophylactic treatment. Methods Retrospective study of 97 pediatric HT recipients between 2010 and 2016...
Article
Purpose To evaluate if the virus found in the myocardium of dilated cardiomyopathy (DCM) pediatric patients persists in the cardiac allograft after heart transplant (HT), and its prognostic implications. Methods Multiplex polymerase chain reaction (PCR) was used to analyze myocardial samples from 48 DCM patients. Subsequently consecutive endomyoca...
Article
Full-text available
Virology: a biomarker for HHV-6 reactivation The human herpesvirus 6 (HHV-6) expresses high levels of small non-coding RNA (sncRNA) molecules early in its reactivation from latency. Bhupesh Prusty from the University of Würzburg, Germany, and colleagues developed a laboratory system for studying HHV-6 infections in a human bone cancer cell line. T...
Article
Chlamydia trachomatis infections have been associated with ovarian cancer by several epidemiological studies. Here, we show that C. trachomatis infected primary human ovarian epithelial cells display elevated oxidative DNA damage. Base excision repair, an important cellular mechanism to repair oxidative DNA lesions, was impaired in infected primary...
Article
Full-text available
Background and main text: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS...
Article
Full-text available
Early-life infections and associated neuroinflammation is incriminated in the pathogenesis of various mood disorders. Infection with human roseoloviruses, HHV-6A and HHV-6B, allows viral latency in the central nervous system and other tissues, which can later be activated causing cognitive and behavioral disturbances. Hence, this study was designed...
Data
HHV-6A and HHV-6B detection through the use of immunofluorescence staining was validated using FFPE sections of HHV-6A and HHV-6B-infected HSB-2 and Molt-3 cells respectively. Uninfected cells served as control.
Data
Representative confocal microscopy images showing Purkinje cell-specific staining for HHV-6A (left) and HHV-6B (right). Cryo-sectioned cerebellar cortex samples were stained using antibodies raised against HHV-6A gp82/105 or HHV-6B OHV3 (Red). HHV-6 positive Purkinje cells are marked with white arrowhead. Purkinje cell specificity was tested using...
Data
Immuno-fluorescence analysis to study HHV-6 infection in astrocytes and microglia within cerebellar cortex samples. (A) Representative images showing positive staining for astrocytes in HHV-6A and HHV-6B negative samples. (B) Representative images showing HHV-6A and -6B positivity only in Purkinje cells. Astrocytes were detected as negative for HHV...
Data
Representative images from confocal image analysis to study HHV-6 infection in astrocytes within cerebellar cortex samples. Red arrowheads point to HHV-6 positive cells whereas white arrowheads point to astrocytes showing HHV-6 positive co-staining. The scale bars represent 200 μm.
Data
Table showing the cause of death for both the cohorts 1 and 2. BPD, bipolar disorder; MDD, major depressive disorder; SCZ, schizophrenia; CON, controls.
Data
Enriched pathway network for the toll-like receptors component of the GSEA results. A connection between nodes arises when there is sufficient similarity between the gene sets of these pathways (based on the Dice coefficient). The node colour represents the q-value (more intensive shades of red correspond to more significant q-values), whereas the...
Data
Table showing median age of all the four types of cases from both cohorts 1 and 2. BPD, bipolar disorder; MDD, major depressive disorder; SCZ, schizophrenia; CON, controls.
Data
Mean (+SD) virus load (per 10e6 cells) for total HHV-6, HHV-6A, and HHV-6B DNA for cohorts 1 and 2. Viral copy numbers were set as 0 for all samples with viral DNA copies below the limit of detection (LOD).
Data
Summary of results from various types of tests carried out on both the cohort of samples.
Data
Summary of gene set enrichment analysis (GSEA) analysis showing significantly enriched pathways.
Data
Real-time based qPCR analysis showing quantification of HHV-6 genome equivalents per cell all the samples from both the cohorts 1 and 2. Mean Cq values as obtained from qPCR analysis and the subsequent calculations are described in detail.
Data
Antibodies used for Immunohistochemistry and Western Blotting.
Article
Full-text available
Chlamydia trachomatis, an obligate intracellular human pathogen, is a major cause of sexually transmitted diseases. Infections often occur without symptoms, a feature that has been attributed to the ability of the pathogen to evade the host immune response. We show here that C. trachomatis paralyses the host immune system by preventing the activati...
Data
PI15 regulation and its effect on chlamydial growth.(A) PI15 is differentially regulated at transcriptional level during Chlamydia and /or HHV-6A infection. HeLa cells were infected with either C. trachomatis or HHV-6A or both for 24 h. Total RNA was extracted and was used for quantitative reverse transcriptase PCR to analyze PI15 mRNA level. hpi,...
Data
Comparison of intra-cellular CPAF localization by different fixation methods. (A) Schematic diagram showing different planes of sectioning of images used for the study of PI15-CPAF co-localization. (B) Confocal images from CPAF or cHtrA stained Chlamydia infected cells fixed with PFA either at room temperature (RT) or at 37°C. DAPI staining was use...
Data
PI15 localizes within the chlamydial inclusion lumen. (A) Validation of PI15-specific antibody staining by RNAi. HeLa cells were either transfected with siRNAs against PI15 or control siRNAs. 72 h post transfection, cells were infected with C. trachomatis. Cells were immunostained using PI15 or Chlamydia-specific Hsp60 (cHsp60) antibodies. Draq5 wa...
Data
CQuantitative analysis of PI15 and CPAF co-localization within inclusions of persistent Chlamydia. (A) Confocal images showing CPAF and PI15 co-localization within two representative persistent chlamydial inclusions infected with wild type Chlamydia (WT Ctr) and HHV-6A. (B) Structured illumination micrograph of a Chlamydia infected HeLa cell immuno...
Data
Functional interaction of CPAF and PI15. (A) CPAF zymogen co-immunoprecipitates with PI15. Co-IP experiments were carried out using T-REx-293 cells that inducibly express PI15-Flag. Cells were induced with 0.1 μg/ml of AHT for 48 h and then infected with a CPAF wildtype (CPAF+) and CPAF mutant (CPAF-) strain, for another 24 h. Total cellular lysate...
Data
Recombinant PI15 protein preparation. Recombinant PI15 proteins were purified from E. coli. Different concentrations of PI15 proteins were separated on a 12% PAGE gel and stained with Coomassie stain (left) or immunoblotted using an antibody against PI15 (right).
Data
3D reconstruction of PI15-CPAF co-staining. Lateral rotation of the 3D projection around Y of C. trachomatis infected HeLa cells stained with CPAF (red channel), PI15 (green channel) and DNA is stained with DAPI (blue channel). Images were acquired in Z-stack on a Leica TCS SP5 confocal platform after fixing and reconstructed from the stacks using...
Data
3D reconstruction from a coronal section of PI15-CPAF co-staining (The cell in entirety is seen in Video 1). Lateral rotation of the 3D projection around Y of C. trachomatis infected HeLa cells stained with CPAF (red channel), PI15 (green channel) and DNA is stained with DAPI (blue channel). Images were acquired in Z-stack on a Leica TCS SP5 confoc...
Data
3D reconstruction from a coronal section of PI15-CPAF co-staining. Diagonal rotation of the 3D projection around Y of C. trachomatis infected HeLa cells stained with CPAF (red channel), PI15 (green channel) and DNA is stained with DAPI (blue channel). Images were acquired in Z-stack on a Leica TCS SP5 confocal platform after fixing and reconstructe...
Article
Full-text available
Obligate intracellular pathogenic Chlamydia trachomatis express several serine proteases whose roles in chlamydial development and pathogenicity are not completely understood. The chlamydial protease CPAF is expressed during the replicative phase of the chlamydial developmental cycle and is secreted into the lumen of the Chlamydia-containing vacuol...
Article
Full-text available
Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are two different species of betaherpesviruses that integrate into sub-telomeric ends of human chromosomes, for which different prevalence rates of integration have been reported. It has been demonstrated that integrated viral genome is stable and is fully retained. However, study of chromosomally integ...
Conference Paper
Full-text available
Background: Oral candidiasis is an independent prognostic factor that can determine the progression of HIV infection. Widespread and repeated use of azole drugs has been implicated as the reason for the emerging fluconazole resistance in Candida strains. The K21 compound is an ethoxylated version of quaternary ammonium silane, with various antimicr...
Article
Full-text available
New antivirals are required to prevent rising antimicrobial resistance from replication inhibitors. The aim of this study was to analyse the range of emerging mutations in herpesvirus by whole genome deep sequencing. We tested human herpesvirus 6 treatment with novel antiviral K21, where evidence indicated distinct effects on virus envelope protein...
Article
Full-text available
Specialized assembly factors facilitate the formation of many macromolecular complexes in vivo. The formation of Sm core structures of spliceosomal U-rich small nuclear ribonucleoprotein particles (UsnRNPs) requires assembly factors united in protein arginine methyltransferase 5 (PRMT5) and survival motor neuron (SMN) complexes. We demonstrate that...
Article
Full-text available
Obligate intracellular bacteria such as Chlamydia trachomatis depend on metabolites of the host cell and thus protect their sole replication niche by interfering with the host cells’ stress response. Here, we investigated the involvement of host microRNAs (miRNAs) in maintaining the viability of C. trachomatis –infected primary human cells. We iden...
Data
Raw data for quantitative analysis of C. trachomatis Cdu1-FLAG infectivity, Mcl-1 stabilization and apoptosis inhibition shown in Figure 3—figure supplement 2.DOI: http://dx.doi.org/10.7554/eLife.21465.013
Data
Raw data for quantitative analysis of Mcl-1 stabilization in Cdu1-expressing HEK 293T cells shown in Figure 5.DOI: http://dx.doi.org/10.7554/eLife.21465.019
Data
Raw data for quantitative analysis of Mcl-1 ring intensity around C. trachomatis pTet/Cdu1 inclusions uninduced and induced for Cdu1 overexpression shown in Figure 6—figure supplement 2.DOI: http://dx.doi.org/10.7554/eLife.21465.025
Data
Raw data for quantitative analysis of Mcl-1 level in UO126-treated HeLa cells infected with C. trachomatis shown in Figure 1—figure supplement 1.DOI: http://dx.doi.org/10.7554/eLife.21465.005
Data
Raw data for quantitative analysis of Mcl-1 stabilization, Mcl-1-ringed inclusion count and calculation of Mcl-1 ring intensity of HeLa cells infected with C. trachomatis wild type and Tn-cdu1 shown in Figure 6.DOI: http://dx.doi.org/10.7554/eLife.21465.022
Data
Plasmids. Listed are all plasmids used in this study to transfect human cells or to transform E. coli or C. trachomatis. If not stated otherwise, constructs were cloned in this study using the oligo nucleotides listed in Supplementary file 4. DOI: http://dx.doi.org/10.7554/eLife.21465.035
Data
Chlamydia trachomatis strains. Listed are all C. trachomatis strains used and generated in this study. All C. trachomatis strains generated by transformation and selection originate from the C. trachomatis LGV L2 (434) (ATCC VR-902B) strain. DOI: http://dx.doi.org/10.7554/eLife.21465.036
Data
Raw data for quantitative analysis of Mcl-1 ubiquitination level shown in Figure 1.DOI: http://dx.doi.org/10.7554/eLife.21465.003
Data
Raw data for analysis of relative enzymatic activity of Cdu1 in Ub-AMC hydrolysis assay shown in Figure 2—figure supplement 1.DOI: http://dx.doi.org/10.7554/eLife.21465.009
Data
Raw data for quantitative analysis of apoptosis resistance analyzed by PARP cleavage and analysis of infectivity after IFNγ-treatment shown in Figure 7.DOI: http://dx.doi.org/10.7554/eLife.21465.027