Download or read book Within host Diversity of Kaposi Sarcoma associated Herpesvirus written by Jan Clement Ang Santiago and published by . This book was released on 2021 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt: Kaposi sarcoma (KS) is a progressive, incurable soft tissue disease that is the most common cancer of men in regions of sub-Saharan African and the second most common among people with HIV. Kaposi Sarcoma-associated Herpesvirus (KSHV) is the infectious cause of KS, but why only a small fraction of those infected develop KS is not understood. Immune status, viral co-infection, host genetics and environmental factors all are likely to play a role. My thesis sought to identify a possible viral genetic component of KS, through an analysis of the diversity of whole KSHV genomes within individuals afflicted by KS. Strain variation or de novo mutations occurring in other oncoviruses have been associated with variations in disease risk, disease manifestation and clinical course. These variations have the potential to become diagnostic biomarkers and help reveal insights into the pathogenicity of the virus. To identify potential tumor-associated mutations in KSHV I analyzed the ~131 kb unique sequence regions of 43 whole KSHV genomes from tumors and oral swabs from 22 individuals and then screened additional tumors by targeted sequencing and ddPCR to better assess the frequency of identified mutations. In total, 65 KS tumors and 18 oral swabs were evaluated from a cohort of 30 study participants with KS, all from the Uganda Cancer Institute. In addition, the major internal repeat regions of the KSHV genome were examined from 16 individuals. The newly developed technologies of duplex Unique Molecular Identifier (dUMI) and single molecule real time sequencing with UMI (SMRT-UMI) were employed to provide an unprecedented accuracy and depth of study of herpesvirus populations within individuals. These studies revealed recurring tumor-associated mutations, specifically an overrepresentation of a specific region encompassing the K5 and K6 genes and inactivating mutations in the K8.1 gene, both of which were found in at least a third of the cohort and had associations with late-stage tumor characteristics. In contrast, the translation potential of full-length Kaposin proteins from IR2 was lost in a majority of individuals, but no tumor association or clinical correlate was identified. Rearrangement breakpoints were sometimes shared between different tumors from the same person, indicating spread by metastases, helper viruses or residual infectivity. In summary, these studies revealed the presence of selection for tumor- and clinical-stage specific changes the KSHV genome. Hypotheses on whether these changes play a role in KS tumor formation, immune evasion and driving persistence in the host are put forth along with proposed experiments to test them. Among them, findings from my thesis suggest that targeted screening of the K5-K6 and K8.1 gene regions can be helpful in tumor classification.
Download or read book Research on Kaposi s sarcoma associated herpesvirus past present and future written by Keiji Ueda and published by Frontiers E-books. This book was released on with total page 185 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has been 16 years since Kaposi's sarcoma-associated herpesvirus (KSHV) was found from Kaposi's sarcoma. Very extensive studies on KSHV have been performed and we now know well that KSHV is actually the very etiologic agent to cause Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease and this virus is an oncogenic DNA virus in such sense. Though a lot of reports have been published, there are lots of enigmas on its epidemiology, entry, lytic replication/induction, viral particle assembly/egress, latency, oncogenesis and so on. At this time point, it is better for us to review what we learned from the studies of this virus and consider what we have to clarify about this virus nature for future by comparing the virus with the other virus research.
Download or read book Kaposi Sarcoma Herpesvirus New Perspectives written by Chris Boshoff and published by Springer Science & Business Media. This book was released on 2006-10-28 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: will follow
Download or read book HIV AIDS Associated Viral Oncogenesis written by Craig Meyers and published by Springer. This book was released on 2018-12-06 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most important aspects of AIDS is the loss of protective immune function in the infected host which leads to increased prevalence of opportunistic infections and cancers. This book specifically addresses viral-induced human cancers associated with AIDS and observed in the AIDS population. It addresses the specific treatment required in this special population and the molecular biology of the causative viral agents.
Download or read book Molecular and Cellular Interactions Between the Host and Herpesviruses written by and published by Frontiers Media SA. This book was released on 2021-11-09 with total page 179 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Human Herpesviruses written by Ann Arvin and published by Cambridge University Press. This book was released on 2007-08-16 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.
Download or read book Kaposi s Sarcoma Associated Herpesvirus Manipulates Host Cell Transcriptional and Translational Pathways to Aid Viral Replication written by Elena May Harrington and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterizing the Molecular Basis for MRNA Targeting and Destruction by the Kaposi s Sarcoma Associated Herpesvirus KSHV Protein SOX written by Sergio Covarrubias and published by . This book was released on 2012 with total page 60 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lytic infection with gamma herpesviruses such as Epstein Barr Virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) results in a global depletion of cellular mRNA, which manifests in a general suppression of host gene expression, termed host shutoff. The importance of targeting cellular gene expression at the posttranscriptional level is highlighted by the observation that many changes in important cellular gene programs result in drastic changes in RNA stability. Hence, virus targeting of host gene expression at this level likely represents an efficient way to change the cellular environment into one the supports maximal viral production. In KSHV, the host shutoff phenotype is caused by virally encoded multifunctional nuclease, SOX, that is conserved throughout all gamma-herpesviruses. Here I provide detailed mechanistic insight into how SOX targets host messages to enact host shutoff activity in cells. I show that with in the cytoplasm, SOX specifically targets conserved mRNA features, which normally promote their efficient expression. Furthermore, I demonstrate that this mechanism of mRNA targeting is conserved across various other viruses, likely demonstrating an evolutionarily convergent strategy. Characterizing how viruses co-op specific cellular factors involved in gene expression will yield a better understanding of the signals that initiate activation of RNA turnover pathways needed for viral replication success.
Download or read book Kaposi s Sarcoma associated Herpesvirus as a Model of the Pathogen host Equilibrium written by and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Kaposi s Sarcoma associated Herpesvirus Transmission and Infection Among Young Zambian Children written by Landon N. Olp and published by . This book was released on 2015 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt: Additionally, next-generation deep sequencing was used to examine KSHV genomic diversity in an endemic setting as the first step to investigate the possible impact of genetic variations on pathogenesis and transmission. We detected distinct phylogenetic clustering between KSHV isolates from Zambia and Western countries, and identified four genes with unprecedented levels of polymorphisms.
Download or read book Quantification Genetic Diversity and Therapeutic Response of Human Herpesvirus 8 in Human Immunodeficiency Virus 1 Infected Patients with Kaposi s Sarcoma written by Taryn Page and published by . This book was released on 2004 with total page 170 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Kaposi s Sarcoma associated Herpesvirus Replication and Transcription Activator Regulates Extracellular Matrix Signal Pathway written by Daniel Pfalmer and published by . This book was released on 2016 with total page 130 pages. Available in PDF, EPUB and Kindle. Book excerpt: Kaposi’s Sarcoma (KS) is a malignancy caused by infection with Kaposi’s Sarcoma-associated Herpesvirus [KSHV; also known as Human Herpesvirus 8 (HHV8)] in which tumor cells show a characteristic ‘spindle-like’ morphology. The transcription factor RTA (Replication and Transcription Activator) is the viral protein responsible for reactivating KSHV from its latent state. Production of RTA in latently infected cells causes a number of viral proteins to be produced and leads to a cascade of gene expression changes in both viral and host genes. Previous work in our lab showed that RTA was capable of reprogramming cells in vitro to display a spindle-like morphology. In this study we aimed to identify the host gene expression changes caused directly by RTA which could be responsible for that reprogramming. To that end, Madin-Darby Canine Kidney cells (MDCK cells) were chosen as a model for KSHV-naïve mammalian cells. Differences in host gene expression levels in a culture of MDCK cells transfected with a plasmid coding for expression of RTA compared to MDCK cells transfected with a similar plasmid lacking the RTA gene were measured by whole transcriptome sequencing (RNA-Seq). Cells containing the RTA-coding plasmid adopted a spindle-like morphology and showed at least a two-fold change in expression level in approximately 180 genes. Those 180 genes were then screened for known associations to signaling pathways in order to determine which might be involved with the morphological changes observed and/or biological significance. The expression levels of the 10 genes identified by that screening were then verified by quantitative real time PCR (qPCR). Of those 10 genes, eight were identified as potentially associated with the morphological changes, including three genes associated with extra cellular matrix (ECM) destruction (MMP9, CTSD, and CTSS) that were down-regulated; two genes associated with blocking ECM destruction (TIMP1 and TIMP2) that were pregulated; two ECM component genes (LAMC2 and COL1A2) that were upregulated; and one gene associated with blocking cell-cell and cell-ECM adhesion (MUC1) that was downregulated. The remaining two genes (MAP2K1 and podoplanin) were identified as potentially biologically significant, but not directly involved in regulating morphology. MAP2K1 is associated with epithelial dedifferentiation and was down-regulated; and the lymphatic endothelial specific marker podoplanin (PDPN) was up-regulated. Taken together, the differences in morphology and gene expression between RTA-producing cells and controls suggest a possible role for RTA in the formation of the spindle cells that characterize Kaposi’s sarcoma.
Download or read book The Role of Host Cell Factors in the Lytic Reactivation of Kaposi s Sarcoma associated Herpesvirus from Latency written by L. Dalton-Griffin and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Role of Host Cell Factors in the Lytic Reactivation of Kaposi s Sarcoma associated Herpesvirus from Latency written by Lucy Dalton-Griffin and published by . This book was released on 2010 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Kaposi Sarcoma Associated Herpesvirus and Heme Oxygenase 1 the Bidirectional Relationship Between Virus and Host written by Sara Botto and published by . This book was released on 2016 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book An Analysis of the Cis and Trans acting Elements of Kaposi s Sarcoma associated Herpesvirus During Latent Infection written by and published by . This book was released on 2014 with total page 418 pages. Available in PDF, EPUB and Kindle. Book excerpt: Kaposi's Sarcoma-associated Herpesvirus (KSHV) is an oncogenic human herpesvirus that is causally associated with at least two malignancies. KSHV is present in proliferating cells of these malignancies primarily in its latent form as a multicopy plasmid. Its persistence in close to 100% of the proliferating tumor cells reveals two important features of its latency; first, the latent genomes have to replicate each cell cycle efficiently enough to ensure that they are retained in a majority of the daughter cells; and second, the latent genes must provide selective advantages, likely to be proliferative and/or anti-apoptotic in nature, to the tumor cells to ensure that the cells that retain them outgrow those that don't. This work describes findings on the necessary cis- and trans-acting factors that contribute to both of these features of KSHV's latency. Each KSHV genome encodes many potential origins of latent replication. Here I have shown that these many origins provide an essential advantage to KSHV allowing the DNAs not only to be synthesized and partitioned into daughter cells efficiently, but also to persist in the dividing cells for a long-term without rearrangement. I have also shown that the correct spacing between KSHV's origins of DNA synthesis is required for them to support synthesis efficiently. Additionally, this work has allowed us to generate a minimal replicon of KSHV that can be used as a model with which aspects of KSHV's latent replication can be studied. I have also provided insights into the selective advantages that latent KSHV provides infected tumor cells by forcing their loss from latently infected cells of Primary Effusion Lymphomas (PEL). The survival of more than 98% of the cells in multiple PEL cell lines tested was inhibited upon the eviction of KSHV genomes, providing direct evidence that KSHV provides survival factors to these cells. Complementation of these KSHV-evicted cells with anti-apoptotic genes was not sufficient to rescue their survival, indicating that the contributions of KSHV to PELs extend beyond protection from apoptosis. Evicting latent KSHV genomes from infected tumor cells could, thus, be therapeutically beneficial for patients with PELs and other KSHV-associated malignancies.
Download or read book Role of Long Non coding RNAs in Kaposi s Sarcoma Associated Herpesvirus Lytic Reactivation written by Wanyu Li and published by . This book was released on 2020 with total page 56 pages. Available in PDF, EPUB and Kindle. Book excerpt: Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, an AIDS-related endothelial malignancy. In an infected cell population, KSHV largely exists as a latent episome, while a small percentage of latent virus undergoes lytic reactivation. The latent-to-lytic switch of KSHV is pathologically important, tightly regulated event that involves extensive host-virus crosstalk. Long non-coding RNAs (lncRNAs) are a diverse class of RNA regulators that have been shown to involve in the life cycles of many different viruses. However, the roles of lncRNAs in KSHV lytic reactivation have been unexplored. This study utilizes two cellular models of KSHV latent infection of different tissue origins to uncover differentially expressed lncRNAs during KSHV lytic reactivation via RNA-seq, revealing lncRNAs that may function in modulating virus lytic replication. Using CRISPR interference (CRISPRi), one of the novel differentially expressed lncRNAs, AC017002.3, was found to positively regulate KSHV early lytic transcript level. Since lncRNAs tend to function in ribonucleoprotein complexes, to address the mechanism by which AC017002.3 functions, RNA affinity pull-down was performed to search for its potential interacting proteins. hnRNP K and ILF2 were found to associate with AC017002.3. While functional validation of possible ribonucleoproteins involving AC017002.3 need to be conducted, this study provides the first evidence that host lncRNAs regulate KSHV lytic reactivation.
