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 A Structural and Functional Analysis of Herpes Simplex Virus Type 1 Glycoprotein L an Essential Component of the Viral Fusogenic Complex written by Michael J. Novotny and published by . This book was released on 1996 with total page 456 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book GENETIC STRUCTURE FUNCTION ANALYSIS OF THE ESSENTIAL GLYCOPROTEIN GB IN HERPES SIMPLEX VIRUS TYPE 1 INDUCED MEMBRANE FUSION VIRAL MEMBRANE PROTEIN written by PHILIP JOHN GAGE and published by . This book was released on 1992 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: cytoplasmic domain, which is essential for gB function in both viral penetration and cell fusion, presenting a paradox since this region of the molecule presumably does not interact with the adjacent cell plasma membrane.

Download or read book Identification of Regions in Herpes Simplex Virus Type 1 Glycoprotein D Critical for Receptor Binding and Membrane Fusion written by Cheryl Rosemarie Jogger and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The ability of HSV to induce membrane fusion is critical to its infection process. First, in order to gain entry into a cell, HSV must fuse its virion envelope with the cell plasma membrane. Second, as an effective means of promoting viral spread, HSV can induce fusion of infected cells with neighboring uninfected cells. Both fusion events are dependent on the binding of gD to an entry receptor, such as HVEM or nectin-1, and on the combined activities of viral gB, gD, gH and gL. The overall goal of this study was to define regions of HSV-1 gD critical for physical and functional interactions with each of the known HSV entry receptors, including nectin-2 and 3-O-S heparan sulfate. Extensive mutational analysis was performed to identify mutations in gD that alter its receptor usage.

Download or read book Differential Requirements for the Syncytial Phenotype of Herpes Simplex Virus Type 1 written by Akua Sarfo and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: HSV-1 encodes four glycoproteins that enable the viral membrane to fuse with the host cell, and this entry complex consists of gD (for receptor-binding), gB (the fusogen), and gH/gL (for signaling between gD and gB). Because this machinery appears on the plasma membrane of infected cells, it must be tightly regulated so that infected cells do not fuse with adjacent uninfected cells. Moreover, the fusion machinery and the proteins that regulate it are also involved in cell-to-cell spread, which enables the virus to move to uninfected cells through lateral junctions so that it can avoid neutralizing antibodies in the host. Syncytial mutants dysregulate this machinery, and cell-cell fusion results in the formation large syncytia, which contain many nuclei bounded by one membrane. Syn variants arise from mutations in any one of four HSV-1 genes, and these include gB, gK, UL20, and UL24. However, the Syn phenotype produced by these mutants is also regulated and requires accessory proteins that are involved in regulating the viral entry machinery. It has been assumed that an accessory protein required for one syn locus would be required across all the loci, and limited data support this. For example, it has been reported that accessory protein UL11 is required for both gBSyn and gKSyn. This dissertation project began with the observation that tegument protein UL21 is required for gBSyn. That is, deletion of the UL21-coding sequence from the gBSyn parent resulted in a virus that was lytic even though the syn mutation was present. Because of the assumption that accessory proteins required for one syn locus would be needed for all four, and because the UL21-coding sequence had been completely deleted, we were surprised to see syncytial variants arising from UL21/gBSyn. Similarly, passage of a virus lacking UL21 in an otherwise wild-type background also resulted in the appearance of syncytial variant viruses. We purified and sequenced these UL21 syncytial variants and found that all these mapped exclusively to glycoprotein K, a virion membrane protein capable of binding gB and thought to modulate membrane fusion events. A number of the changes we found were not gKSyn alleles described in the literature, so we followed up by creating recombinant viruses with these changes to confirm that they were indeed novel gKSyn alleles. We also confirmed that UL21 is not necessary for gKSyn-mediated fusion by building recombinant viruses with gK syncytial substitutions lacking UL21, which were immediately fusogenic following viral DNA transfection into Vero cells. Because a differential requirement for an accessory protein in syncytia formation had not been described in the literature, we tested additional gBSyn alleles for their requirement for UL21, as well as testing the requirement for UL21 in the context of UL20 and UL24 syncytial mutations. These studies revealed that UL21 is only required for gBSyn and not for any of the other syn loci. The viral proteins required for syncytia formation are thought to be similar to those needed for direct cell-to-cell spread. Herpesviruses use this spreading mechanism to avoid antibodies that could inactivate it within the infected host. To test whether UL21 is a component of the cell-to-cell spreading machinery, we examined the ability of the null virus to infect neighboring cells in the presence of neutralizing antibodies. For this, no syn mutations were present. Unlike the wild-type control, UL21 virus was found to be greatly impaired in its ability to infect adjacent cells. We hypothesize that this spreading defect provides a selective pressure for syn mutations, which compensate for the cell-to-cell spreading defect. Having identified the first example of a differential requirement for the Syn phenotype, we tested two viral proteins, gE and gI, that are well known to be required for cell-to-cell spread and the gBSyn phenotype. We tested the requirement for these two glycoproteins across the gK, UL20, and UL24Syn backgrounds. They seemed to be the logical next Syn accessory proteins to test because UL21, along with tegument proteins UL11 and UL16 forms a complex on the gE cytoplasmic tail, which is known to modulate gB function in the context of the syncytial mutation gB.A855V. We hypothesized that the requirements for gE and gI would be the same because these two proteins form a heterodimer, and based on the UL21 results, we hypothesized that neither of these glycoproteins would be required for gKSyn, UL20Syn, or UL24Syn. We were surprised to find that gE and gI are differentially required both across and within the syn loci, with UL24 syncytial mutations exhibiting a strict requirement for both gE and gI, UL20 syncytial mutations displaying a strict requirement for gE but not gI, and gK syncytial mutations displaying no requirement for gI, but an allele-specific requirement for gE. The differential requirement for gE within the gKSyn locus is the first example for an accessory protein being differentially required within one syn locus. In the course of our experiments, we also found evidence that additional syn loci might exist. This came from studies of a mutant virus that 1) lacks the UL11-binding site within the cytoplasmic tail of gE and 2) also has a gBSyn mutation (gECT(25)/gB.A855V). This virus was initially lytic when the DNA was transfected into cells; however, variants quickly arose that had the ability to fuse cells. We purified several independent variants, and confirmed that the two original mutations were present. Then, we hypothesized that the variants had gained a second syn mutation. Surprisingly, sequencing of the other three syn loci in these variants revealed no mutations. Because we could not predict what change(s) had occurred, a whole-genome, deep sequencing approach was used. The results revealed that all had mutations that prevented the expression of glycoprotein C, a viral protein implicated in adsorption of the virus to cells but also described in the literature as decidedly not a syn locus. This provides the first evidence that gC regulates the fusion activity of gB.

Download or read book Identification and Characterization of Low PH triggered Conformational Changes in the Herpes Simplex Virus Glycoprotein B written by Stephen Dollery and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Herpesviruses can enter host cells by pH-dependent endocytic pathways in a cell-specific manner. The role of pH in herpesvirus endocytosis is unclear. Herpes simplex virus (HSV) is a paradigm for virus membrane fusion via a complex of glycoproteins. HSV glycoproteins B, D and the heterodimer H-L are necessary and sufficient for membrane fusion. This work analyzes the structure and function of HSV glycoproteins B, D, and H-L at neutral pH, and at the physiological low-pH encountered during endocytic entry. It is demonstrated that mildly acidic low pH triggers specific conformational changes in HSV gB at a pH of 5.7 to 6.0. The antigenic structure of gB functional region I that is critical for fusion is specifically altered by mildly acidic pH both in vitro and during entry into host cells. Point mutations within gB functional region 1 that block membrane fusion still allow conformational changes in region 1. This suggests that specific hydrophobic residues are essential for fusion domain insertion into the host cell membrane but not conformational change. The detected conformational changes were reversible, similar to other class III fusion glycoproteins. Exposure to mildly acidic pH directly triggered the fusion function of HSV glycoproteins and caused gB, but not other glycoproteins, to become more hydrophobic. The oligomeric conformation of gB is altered at a similar pH range. In addition, several approaches were used to monitor gB throughout glycoprotein synthesis and maturation. It is shown that gB may cotranslationally fold and oligomerize as it is synthesized on the ribosome. As gB matures it then alters conformation and/or binding partner to form antigenically distinct populations of gB within the cell and virion. I conclude that intracellular low pH induces changes in gB conformation that, together with additional triggers such as receptor-binding, are essential for virion-cell fusion during herpesviral entry by endocytosis.

Download or read book Herpes Simplex Virus Type 1 HSV 1 UL31 UL33 and UL34 Proteins Play Essential Roles in Herpesvirion Morphogenesis written by Ashley Elizabeth Reynolds and published by . This book was released on 2002 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Structure function Analysis of the Virulence Protein Icp34 5 from Herpes Simplex Virus Type 2 written by Somik Chatterjee and published by . This book was released on 2009 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Glycoprotein M and ESCRT in Herpes Simplex Virus Type 1 Assembly written by Yudan Ren and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Herpes simplex virus type 1 (HSV-1) has a large linear double-stranded DNA genome in an icosahedral capsid shell, a cell-derived lipid envelope and a proteinaceous tegument layer. There are over fifty viral proteins and many host proteins identified in HSV-1 virions. The final formation of mature virus particles requires the membrane wrapping of tegumented capsids in the cytoplasm, a process termed secondary envelopment. This process involves the coordination of numerous viral and cellular proteins and results in double-membrane structures with enveloped virions contained within cellular vesicles. Mature viruses are then released through the fusion of these virion-containing vesicles and plasma membranes. This thesis describes investigation into the functions of viral glycoprotein M (gM) and the cellular Endosomal Sorting Complexes Required for Transport (ESCRT) in secondary envelopment. Firstly, it has been reported that gH/L can be efficiently internalised and targeted to the TGN by the co-expression of gM in transfection assays. In order to examine the role of gM in guiding the localisation of viral proteins in infected cells, a HSV-1 gM deletion virus (∆gM), and its revertant virus were constructed. The major phenotype demonstrated was that the absence of gM caused the internalisation of cell surface gH/L to be inhibited and higher levels of gH/L to be observed on the cell surface. Further, lower levels of gH/L were detected in purified ∆gM virions, which was in agreement with the delayed entry kinetics, smaller plaque sizes and greater replication deficits at low multiplicity of infection observed in ∆gM infected cells. Over all the results presented in this thesis demonstrate that in infected cells the efficient incorporation of gH/L into virions relies on the function of gM in HSV-1. Secondly, during HSV-1 secondary envelopment the budding and scission of the viral envelope from the host membrane share topological similarities with the formation of intraluminal vesicle in multivesicular bodies, retrovirus budding, and abscission at the end of cytokinesis, processes that require the cellular ESCRT machinery. There are four multiprotein ESCRT complexes and many associated proteins involved in their regulation. It has been previously shown that the ESCRT-III complex and a functional ATPase VPS4 are required for HSV-1 secondary envelopment, but different from the strategy utilised by HIV-1, the recruitment of ESCRT during HSV-1 infection is independent of TSG101 and/or ALIX. Data presented in this thesis demonstrate that CHMP4A/B/C proteins of the ESCRT-III complex are specifically crucial for HSV-1 secondary envelopment. Simultaneous depletion of CHMP4A/B/C proteins significantly inhibited HSV-1 replication. Ultrastructure analysis revealed that there were virtually no extracellular virions in CHMP4A/B/C depleted samples while more free capsids were observed in the cytoplasm, although the nuclear capsids and primary envelopment events appeared to be normal. In order to identify interactions between HSV-1 and ESCRT proteins, 22 HSV-1 tegument proteins were cloned and tested against a panel of ESCRT and ESCRT-associated proteins in yeast two-hydrid assays. Analysis of positive hits from yeast two-hybrid interaction screens using GST pull-down, co-immunoprecipitation and protein co-localisation assays have validated interactions of pUL47 with CC2D1A/1B, CIN85, CHMP6 and ALIX, pUL46 and pUL49 with CC2D1A/1B and CIN85, and pUL16 with CC2D1A/1B. Furthermore, the newly identified ESCRT associated proteins CC2D1A and CC2D1B have been detected in purified virions. The role of the identified ESCRT proteins in HSV-1 replication has been investigated using siRNA depletion. Unfortunately siRNA depletions of the various ESCRT candidates individually or in combinations did not show any significant effect on HSV-1 replication. Overall these data suggest that unlike HIV and other retroviruses, HSV-1 has evolved multiple parallel pathways to hijack the ESCRT machinery to facilitate its replication, particularly, through the interactions that lead directly to the recruitment of CHMP4A/B/C proteins. Disruption of some of these pathways did not prevent HSV-1 replication in tissue culture, suggesting any one potential pathway is sufficient for ESCRT recruitment to sites of HSV-1 assembly.

Download or read book The Epstein Barr Virus written by M. A. Epstein and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 467 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Epstein-Barr virus was discovered 15 years ago. Since that time an immense body of information has been accumu lated on this agent which has come to assume great signifi cance in many different fields of biological science. Thus, the virus has very special relevance in human medicine and oncology, in tumor virology, in immunology, and in mole cular virology, since it is the cause of infectious mononu cleosis and also the first human cancer virus, etiologically related to endemic Burkitt's lymphoma and probably to nasopharyngeal carcinoma. In addition, continuous human lymphoid cell lines initiated and maintained by the transform ing function of the virus genome provide a laboratory tool with wide and ever-growing applications. Innumerable papers on the Epstein-Barr virus have ap peared over recent years and reports of work with this agent now constitute a veritable flood. The present book provides the first and only comprehensive, authoritative over-view of all aspects of the virus by authors who have been the original and major contributors in their particular disciplines. A complete and up-to-date survey of this unique and important agent is thus provided which should be of great interest to experts, teachers, and students engaged in cancer research, virology, immunology, molecular biology, epide miology, and cell culture. Where topics have been dealt with from more than one of these viewpoints, some inevitable overlap and duplication has resulted; although this has been kept to a minimum, it has been retained in some places because of positive usefulness.

Download or read book Cell Biology of Herpes Viruses written by Klaus Osterrieder and published by Springer. This book was released on 2017-05-20 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: Herpes viruses are widely distributed in nature, causing disease in organisms as diverse as bivalves and primates, including humans. Each virus appears to have established a long-standing relationship with its host, and the viruses have the ability to manipulate and control the metabolism of host cells, as well as innate and adaptive antiviral immune responses. Herpes viruses maintain themselves within hosts in a latent state resulting in virus persistence for years – usually for the life span of the hosts. Herpes viruses comprise a large number of pathogens with diverse cellular targets and biological consequences of infection. What they have in common is their structure and the fact that they establish a dormant (latent) infection in their hosts that usually persists for life. The reviews here will highlight the general principles of herpes virus infection, with equal attention to overall principle and important difference. Also, the cell type- and life-style dependent differences in the establishment and maintenance of virus persistence will be covered.

Download or read book Genetics and Functions of Herpes Simplex Virus Type 1 Membrane Proteins in Virus induced Cell Fusion Virion Morphogenesis and Egress written by Jeffrey M. Melancon 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 Structural Mechanics of Class 1 Viral Membrane Fusion Proteins written by Mark Alexander Benhaim and published by . This book was released on 2020 with total page 145 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein-mediated membrane fusion is a highly regulated biological process essential for cellular and organismal functions and infection by enveloped viruses. During viral entry, the membrane fusion reaction is catalyzed by specialized protein machinery on the viral surface. These viral fusion proteins undergo a series of dramatic structural changes during membrane fusion where they engage, remodel, and ultimately fuse with the host membrane. The structural and dynamic nature of these conformational changes and their impact on the membranes have long-eluded characterization. Furthermore, the native pre-fusion structural and conformational dynamics of these fusion machines remains unclear as the conventional structural approaches employed by structural biologists are not well suited for studying these dynamic protein machines on the viral surface. The objective of this dissertation is to characterize the complete mechanism of Influenza virus hemagglutinin (HA) fusion activation and membrane fusion, and to profile and characterize the structural and conformational dynamics of the HIV-1 Env fusion glycoprotein on the viral surface. In chapter 2 I use continuous labeling HDX-MS to characterize the structural dynamics and conformational homogeneity of the HIV-1 Env fusion glycoprotein on the surface of two distinct engineered and authentic viral vaccine platforms. By HDX-MS we observed significant amounts of non-native Env present in one vaccine platform, whereas all Env present in the other resembled trimeric Env in the closed conformation. In chapter 3, I use pulse labeling HDX-MS to characterize the mechanism of HA fusion activation and HA mediated membrane fusion in situ using whole infectious virions. Our data reveal how concurrent reorganizations at the HA1 receptor binding domain interface and HA2 fusion subunit produce a dynamic fusion intermediate ensemble in full-length HA. In contrast, the soluble HA ectodomain transitions directly to the post-fusion state with no observable intermediate. These data provide unprecedented insight into the structural mechanics of HA which has served as the prototypical class 1 viral fusion protein and informed our understanding about how all class 1 viral fusion proteins function. In chapter 4 I present developments and improvements on the HDX-MS workflows that will enable more complete characterizations of HA's mechanism and the structural and conformational dynamics of other class 1 viral fusion proteins. Together these works have dramatically furthered our understanding of the structural mechanics of class 1 fusion proteins and lay the foundation for future studies on influenza virus and other enveloped viruses and their membrane fusion machinery.

Download or read book Human Cytomegalovirus written by Thomas E. Shenk and published by Springer Science & Business Media. This book was released on 2008-05-09 with total page 477 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume has gathered some of the experts in the field to review aspects of our understanding of CMV and to offer perspectives of the current problems associated with CMV. The editors and authors hope that the chapters will lead to a better understanding of the virus that will assist in the development of new and unique antivirals, a protective vaccine, and a full understanding of CMV's involvement in human disease.

Download or read book Origin and Evolution of Viruses written by Esteban Domingo and published by Elsevier. This book was released on 2008-06-23 with total page 573 pages. Available in PDF, EPUB and Kindle. Book excerpt: New viral diseases are emerging continuously. Viruses adapt to new environments at astounding rates. Genetic variability of viruses jeopardizes vaccine efficacy. For many viruses mutants resistant to antiviral agents or host immune responses arise readily, for example, with HIV and influenza. These variations are all of utmost importance for human and animal health as they have prevented us from controlling these epidemic pathogens. This book focuses on the mechanisms that viruses use to evolve, survive and cause disease in their hosts. Covering human, animal, plant and bacterial viruses, it provides both the basic foundations for the evolutionary dynamics of viruses and specific examples of emerging diseases. - NEW - methods to establish relationships among viruses and the mechanisms that affect virus evolution - UNIQUE - combines theoretical concepts in evolution with detailed analyses of the evolution of important virus groups - SPECIFIC - Bacterial, plant, animal and human viruses are compared regarding their interation with their hosts

Download or read book Structural and Functional Study of Bovine Herpesvirus 1 Glycoprotein B in the Interaction with Madin Darby Bovine Kidney Cells written by and published by . This book was released on 1996 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Entry of herpesviruses is mediated by the interactions between viral glycoproteins and cellular receptors. Among these glycoproteins, gB plays an important role. In this study, my major focus was to study gB's functions in the virus entry process and the structural requirements for gB to conduct its functions. The virus model in my study is bovine herpesvirus 1 (BHV-1), a member of the alphaherpesviruses. BHV-1 gB is a type I integral membrane protein with a potential transmembrane anchor at the C-terminal region. A cleavage site in the middle divides this molecule into two subunits, gBb and gBc. In this study, a truncated gB, gBt (residues 1 to 763), and N-terminal subunit, gBb (residues 1 to 505), were first expressed under the control of the bovine heat-shock protein 70A (hsp70A) gene promoter in stably transfected Madin Darby bovine kidney (MDBK) cells. Both forms of gB were secreted into the medium with apparent molecular weights as anticipated, and they were reactive to all gB-specific monoclonal antibodies used in this study. Affinity-purified gBt and gBb were able to elicit antibody responses in mice to an extent comparable to those induced by authentic gB. These results suggest that gBt and gBb retain the structural and antigenic properties of authentic gB. Furthermore, the intracellular processing of gBt and gBb was similar to that of authentic gB in virus-infected cells. Finally, gBt was proteolytically cleaved after conversion of the high mannose-containing precursor to the mature form. These truncated gBs that were prepared served as reagents for the core of my studies. BHV-I gB can bind to heparin sulfate (HS) and another non-HS receptor on MDBK cells. We assume that high-affinity binding to the non-HS receptor is important for BHV-1 infectivity. BHV-1 gB forms dimers in infected cells and in virions, and its dimerization domain may be located between residues 506 to 763. The cytoplasmic domain of BHV-1 gB is important for the existence of the high-aff.

Download or read book Heparanase written by Israel Vlodavsky and published by Springer Nature. This book was released on 2020-04-09 with total page 871 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by internationally recognized leaders in Heparanase biology, the book’s eight chapters offer an opportunity for scientists, clinicians and advanced students in cell biology, tumor biology and oncology to obtain a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications. Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.