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  1. Article ; Online: Revisiting the genomes of herpesviruses

    Bhupesh K Prusty / Adam W Whisnant

    eLife, Vol

    2020  Volume 9

    Abstract: Combining integrative genomics and systems biology approaches has revealed new and conserved features in the genome of human herpesvirus 6. ...

    Abstract Combining integrative genomics and systems biology approaches has revealed new and conserved features in the genome of human herpesvirus 6.
    Keywords human herpesvirus 6 ; RNA-seq ; ribosome profiling ; genome annotations ; herpesvirus ; transcriptomics ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Tissue specific signature of HHV-6 infection in ME/CFS

    Francesca Kasimir / Danny Toomey / Zheng Liu / Agnes C. Kaiping / Maria Eugenia Ariza / Bhupesh K. Prusty

    Frontiers in Molecular Biosciences, Vol

    2022  Volume 9

    Abstract: First exposure to various human herpesviruses (HHVs) including HHV-6, HCMV and EBV does not cause a life-threatening disease. In fact, most individuals are frequently unaware of their first exposure to such pathogens. These herpesviruses acquire lifelong ...

    Abstract First exposure to various human herpesviruses (HHVs) including HHV-6, HCMV and EBV does not cause a life-threatening disease. In fact, most individuals are frequently unaware of their first exposure to such pathogens. These herpesviruses acquire lifelong latency in the human body where they show minimal genomic activity required for their survival. We hypothesized that it is not the latency itself but a timely, regionally restricted viral reactivation in a sub-set of host cells that plays a key role in disease development. HHV-6 (HHV-6A and HHV-6B) and HHV-7 are unique HHVs that acquire latency by integration of the viral genome into sub-telomeric region of human chromosomes. HHV-6 reactivation has been linked to Alzheimer’s Disease, Chronic Fatigue Syndrome, and many other diseases. However, lack of viral activity in commonly tested biological materials including blood or serum strongly suggests tissue specific localization of active HHV-6 genome. Here in this paper, we attempted to analyze active HHV-6 transcripts in postmortem tissue biopsies from a small cohort of ME/CFS patients and matched controls by fluorescence in situ hybridization using a probe against HHV-6 microRNA (miRNA), miR-aU14. Our results show abundant viral miRNA in various regions of the human brain and associated neuronal tissues including the spinal cord that is only detected in ME/CFS patients and not in controls. Our findings provide evidence of tissue-specific active HHV-6 and EBV infection in ME/CFS, which along with recent work demonstrating a possible relationship between herpesvirus infection and ME/CFS, provide grounds for renewed discussion on the role of herpesviruses in ME/CFS.
    Keywords HHV-6 ; ME/CFS ; EBV ; epstein-barr virus ; herpesvirus ; viral pathology ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Chronic persistent HHV‐6B infection after sulfasalazine‐induced DRESS with demonstration of HHV‐6 encoded small noncoding RNAs (sncRNAs) in Crohn’s‐like colitis

    Vincent Descamps / Agnès Gautheret‐Dejean / Anne‐Laure Pelletier / Pascale Bonnafous / Lydia Deschamps / Bhupesh K. Prusty

    Clinical Case Reports, Vol 9, Iss 2, Pp 841-

    Case report

    2021  Volume 844

    Abstract: Abstract 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 ... ...

    Abstract Abstract 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 looking for HHV‐6 reactivation in DRESS.
    Keywords Crohn's disease ; drug reaction with eosinophilia and systemic symptoms ; drug‐induced hypersensitivity syndrome ; human herpesvirus 6B ; Medicine ; R ; Medicine (General) ; R5-920
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Chromosomal integration of HHV-6A during non-productive viral infection

    Nitish Gulve / Celina Frank / Maximilian Klepsch / Bhupesh K. Prusty

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 11

    Abstract: Abstract 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 ... ...

    Abstract Abstract 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 integrated viral genome in individuals carrying inherited HHV-6 (iciHHV-6) showed unexpected number of viral DR copies. Hence, we created an in vitro infection model and studied retention of full or partial viral genome over a period of time. We observed an exceptional event where cells retained viral direct repeats (DRs) alone in the absence of the full viral genome. Finally, we found evidence for non-telomeric integration of HHV-6A DR in both cultured cells and in an iciHHV-6 individual. Our results shed light on several novel features of HHV-6A chromosomal integration and provide valuable information for future screening techniques.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Decoding murine cytomegalovirus.

    Manivel Lodha / Ihsan Muchsin / Christopher Jürges / Vanda Juranic Lisnic / Anne L'Hernault / Andrzej J Rutkowski / Bhupesh K Prusty / Arnhild Grothey / Andrea Milic / Thomas Hennig / Stipan Jonjic / Caroline C Friedel / Florian Erhard / Lars Dölken

    PLoS Pathogens, Vol 19, Iss 5, p e

    2023  Volume 1010992

    Abstract: The genomes of both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) were first sequenced over 20 years ago. Similar to HCMV, the MCMV genome had initially been proposed to harbor ≈170 open reading frames (ORFs). More recently, omics ... ...

    Abstract The genomes of both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) were first sequenced over 20 years ago. Similar to HCMV, the MCMV genome had initially been proposed to harbor ≈170 open reading frames (ORFs). More recently, omics approaches revealed HCMV gene expression to be substantially more complex comprising several hundred viral ORFs. Here, we provide a state-of-the art reannotation of lytic MCMV gene expression based on integrative analysis of a large set of omics data. Our data reveal 365 viral transcription start sites (TiSS) that give rise to 380 and 454 viral transcripts and ORFs, respectively. The latter include >200 small ORFs, some of which represented the most highly expressed viral gene products. By combining TiSS profiling with metabolic RNA labelling and chemical nucleotide conversion sequencing (dSLAM-seq), we provide a detailed picture of the expression kinetics of viral transcription. This not only resulted in the identification of a novel MCMV immediate early transcript encoding the m166.5 ORF, which we termed ie4, but also revealed a group of well-expressed viral transcripts that are induced later than canonical true late genes and contain an initiator element (Inr) but no TATA- or TATT-box in their core promoters. We show that viral upstream ORFs (uORFs) tune gene expression of longer viral ORFs expressed in cis at translational level. Finally, we identify a truncated isoform of the viral NK-cell immune evasin m145 arising from a viral TiSS downstream of the canonical m145 mRNA. Despite being ≈5-fold more abundantly expressed than the canonical m145 protein it was not required for downregulating the NK cell ligand, MULT-I. In summary, our work will pave the way for future mechanistic studies on previously unknown cytomegalovirus gene products in an important virus animal model.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: HHV-6 encoded small non-coding RNAs define an intermediate and early stage in viral reactivation

    Bhupesh K. Prusty / Nitish Gulve / Suvagata Roy Chowdhury / Michael Schuster / Sebastian Strempel / Vincent Descamps / Thomas Rudel

    npj Genomic Medicine, Vol 3, Iss 1, Pp 1-

    2018  Volume 10

    Abstract: 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 ... ...

    Abstract 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. They reawakened the virus with a drug stimulus and detected several sncRNAs but few other viral RNAs that might promote replication or protein production. They term this unique stage of the viral life cycle ‘transactivation’, and show that it alters both host and viral physiology. The authors also describe a teenage girl with high sncRNA levels in her blood who fell ill after an acne drug spurred the reactivation of a dormant HHV-6 infection. They thus argue that sncRNAs could serve as an early diagnostic indicator of HHV-6 reactivation.
    Keywords Medicine ; R ; Genetics ; QH426-470
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Detection of parvovirus B19 and human herpesvirus 6 in pediatric dilated cardiomyopathy

    Bibhuti B Das / Bhupesh K Prusty / Jianli Niu / Meei-Li Huang / Haiying Zhu / Eva Eliassen / Jane M Kuypers / Keith R Jerome

    Annals of Pediatric Cardiology, Vol 13, Iss 4, Pp 301-

    Impact after heart transplantation

    2020  Volume 308

    Abstract: Objectives: The aim of this study is to evaluate HHV-6 and PVB19 infection using polymerase chain reaction (PCR) and immunofluorescent assay (IFA) in the myocardium of pediatric patients with dilated cardiomyopathy (DCM) and the impact of viral ... ...

    Abstract Objectives: The aim of this study is to evaluate HHV-6 and PVB19 infection using polymerase chain reaction (PCR) and immunofluorescent assay (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 samples from 48 pediatric DCM patients and 10 control subjects. Of the 48 DCM patients, 44 underwent HT. After HT, consecutive endomyocardial biopsy (EMB) samples were analyzed for the presence of PVB19 and HHV-6 antigens using IFA and the patients were evaluated for rejections, coronary vasculopathy, and graft loss. Results: Of the 48 DCM patients, 14 had positive viral PCR results in explanted/autopsy hearts. Among them, PVB19 was found in 8/48, HHV6 in 4/48, both PVB19 and HHV6 in 1/48, and enterovirus in one, but no adenovirus was found. The EMB samples obtained after HT were positive for PVB19 and HHV-6 in 7/44 and 3/44 cases, respectively. Viral presence in both the explanted heart and the cardiac allograft was demonstrated in 4 patients, 3 of whom were positive for PVB19, and one of whom was positive for HHV-6 pretransplant. Coronary vasculopathy and graft loss were more common in patients with PVB19-positive myocardial tissues versus those who were PVB19-negative. Conclusions: There is an association between PVB19 and HHV-6 infection and DCM in children. The study suggests the persistence of PVB19 and HHV-6 in the host can lead to subsequent viral reactivation in the transplanted heart, even in those recipients who do not have active myocarditis. PVB19 in the cardiac allograft tended toward higher adverse post-HT events.
    Keywords cardiotropic viruses ; coronary vasculopathy ; dilated cardiomyopathy ; immunofluorescent assay ; pediatric heart transplantation ; polymerase chain reaction ; Medicine ; R ; Pediatrics ; RJ1-570 ; Diseases of the circulatory (Cardiovascular) system ; RC666-701
    Subject code 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Wolters Kluwer Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27

    Xiuye Wang / Thomas Hennig / Adam W. Whisnant / Florian Erhard / Bhupesh K. Prusty / Caroline C. Friedel / Elmira Forouzmand / William Hu / Luke Erber / Yue Chen / Rozanne M. Sandri-Goldin / Lars Dölken / Yongsheng Shi

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Herpes simplex virus-1 (HSV-1) infection disrupts transcription termination (DoTT) of host genes, but underlying mechanisms are unclear. Here, Wang et al. show that the HSV-1 immediate early protein ICP27 induces DoTT through interaction with the mRNA 3’ ...

    Abstract Herpes simplex virus-1 (HSV-1) infection disrupts transcription termination (DoTT) of host genes, but underlying mechanisms are unclear. Here, Wang et al. show that the HSV-1 immediate early protein ICP27 induces DoTT through interaction with the mRNA 3’ processing factor CPSF and disruption of the processing complex.
    Keywords Science ; Q
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: GP96 interacts with HHV-6 during viral entry and directs it for cellular degradation.

    Bhupesh K Prusty / Christine Siegl / Nitish Gulve / Yasuko Mori / Thomas Rudel

    PLoS ONE, Vol 9, Iss 12, p e

    2014  Volume 113962

    Abstract: CD46 and CD134 mediate attachment of Human Herpesvirus 6A (HHV-6A) and HHV-6B to host cell, respectively. But many cell types interfere with viral infection through rapid degradation of viral DNA. Hence, not all cells expressing these receptors are ... ...

    Abstract CD46 and CD134 mediate attachment of Human Herpesvirus 6A (HHV-6A) and HHV-6B to host cell, respectively. But many cell types interfere with viral infection through rapid degradation of viral DNA. Hence, not all cells expressing these receptors are permissive to HHV-6 DNA replication and production of infective virions suggesting the involvement of additional factors that influence HHV-6 propagation. Here, we used a proteomics approach to identify other host cell proteins necessary for HHV-6 binding and entry. We found host cell chaperone protein GP96 to interact with HHV-6A and HHV-6B and to interfere with virus propagation within the host cell. In human peripheral blood mononuclear cells (PBMCs), GP96 is transported to the cell surface upon infection with HHV-6 and interacts with HHV-6A and -6B through its C-terminal end. Suppression of GP96 expression decreased initial viral binding but increased viral DNA replication. Transient expression of human GP96 allowed HHV-6 entry into CHO-K1 cells even in the absence of CD46. Thus, our results suggest an important role for GP96 during HHV-6 infection, which possibly supports the cellular degradation of the virus.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection

    Christine Siegl / Bhupesh K. Prusty / Karthika Karunakaran / Jörg Wischhusen / Thomas Rudel

    Cell Reports, Vol 9, Iss 3, Pp 918-

    2014  Volume 929

    Abstract: Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is ... ...

    Abstract Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.
    Keywords Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2014-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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