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 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 Genetics of Herpes Simplex Virus Type 1 Tegument Proteins Involved in Virion Morphogenesis and Egress written by Preston Fulmer and published by . This book was released on 2007 with total page 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 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 Herpes Simplex Virus Type I HSV 1 induced Cell Fusion written by Tracy L. Terry-Allison and published by . This book was released on 1999 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Herpes Simplex Virus Type 1 UL31 and UL34 Proteins and Their Roles in Viral Envelopment at the Inner Nuclear Membrane written by Li Liang and published by . This book was released on 2005 with total page 438 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Herpes Simplex Virus Type 1 written by Kari Lynn Roberts and published by . This book was released on 2011 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: Herpes simplex virus type 1 (HSV-1) replicates in the nucleus and buds through the nuclear membrane to access the cytosol and complete the maturation process. The HSV-1 protein pUL31, along with its binding partner, pUL34, has been previously shown to be required for nucleocapsids to successfully bud through the nuclear membrane. pUL31 is also required for efficient viral DNA synthesis and packaging. After the HSV-1 exits the nucleus, the capsid acquires several accessory proteins (tegument) and finally a mature envelope by budding into vesicles of the trans-Golgi network (TGN). These virion-laden vesicles traffic toward the cell periphery and through cortical actin until ultimately the virion is secreted upon fusion of the TGN vesicle with the plasma membrane. The data presented here reveals new roles for pUL31, as cells infected with a UL31-null virus were delayed for viral gene expression as well as activation of NF[kappa]B and c-Jun N-terminal kinase (JNK) in multiple cell lines. At least one representative from each kinetic class of viral genes was examined at various times post infection. The protein expression defects were not caused by a failure to enter cells, was not rescued by ICP27 expressed in trans and correlated with NF[kappa]B activation. The data shows that these defects were not observed in the absence of the pUL31 binding partner, pUL34, and that while most pUL31 is expressed at late times post infection, low levels are detectable as early as 2 hours post infection. Data presented in this work also demonstrates a role for the actin motor myosin Va in the secretion of HSV-1 virions. Expression of two isoforms of dominant negative myosin Va (DN-myoVa) decreased virion secretion by 5075% as well as significantly decreased surface expression of viral glycoproteins B, M and D. DN-myoVa colocalized with TGN markers and the conformation of native myosin Va in infected cells was altered by 4 hours post infection. These data suggest that myosin Va is involved in the egress of virion-laden TGN vesicles as they transit through cortical actin toward the plasma membrane.

Download or read book Roles of the Herpes Simplex Virus 1 U L17 and U L28 Genes in Viral DNA Cleavage and Packaging written by Naomi Sachiko Taus and published by . This book was released on 1999 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 Role of Cell Surface Heparan Sulfate in the Binding and Entry of Herpes Simplex Virus and in Virus induced Cell Fusion written by Mei-Tsu Shieh and published by . This book was released on 1992 with total page 312 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 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 The Functional Role of Herpes Simplex Virus Type 1 HSV 1 Glycoproteins in Induction of Cell Fusion written by Ali Saharkhiz-Langroodi and published by . This book was released on 1996 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Dissertation Abstracts International written by and published by . This book was released on 2005 with total page 794 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Host And Viral Factors Involved In Regulation Of Nuclear Egress Of Herpes Simplex Virus written by Fan Mou and published by . This book was released on 2009 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The nascent nucleocapsids of Herpes Simplex Virus (HSV) egress from the infected cell nuclei by budding at the inner nuclear membrane (INM), and become enveloped primary virions in the perinuclear space. The envelope then fuses with the outer nuclear membrane (ONM) and the capsids are released into the cytosol, where they acquire tegument proteins and the final envelope at the trans-Golgi network and are delivered to the extracelluar space via secretory vesicles. This complicated process involves interactions between both viral and host factors. The products of viral UL31 and UL34 genes form a complex on the INM that is essential to initiate the primary envelopment reaction. The proper positioning of this complex requires a kinase encoded by the viral US3 gene. In the absence of pUS3 kinase activity, pUL31/pUL34 complexes aggregate on the nuclear rim and perinuclear virions accumulate within invaginations of the INM. I discovered that the nuclear lamina was dramatically perforated near those pUL31/pUL34 aggregations, and identified lamin A/C as a putative substrate of US3 kinase in vitro. The kinase activity was found to be sufficient to induce partial dissolution of lamin A/C from permeabilized cell nuclei. Two-dimensional electrophoretic analyses confirmed that lamin A/C was phosphorylated in HSV-infected cells, and the optimal phosphorylation required US3 kinase activity. These data suggest that US3 kinase activity regulates HSV-1 capsid nuclear egress at least in part by phosphorylation of lamin A/C. Lamins A/C and B1 were shown to interact with pUL34. To determine the roles of these interactions on viral infectivity and pUL34 targeting, the localization of pUL34 was examined in lamin knockout mouse embryonic fibroblasts (MEFs) in the presence or absence of pUS3 kinase activity. It was determined that both lamin proteins directly or indirectly modified pUL34 distribution but neither was required for its INM targeting during viral infection. The elimination of lamin B1 made cells less permissive for viral replication, whereas lamin A/C was dispensable for viral infection. Furthermore, in cells infected by the US3 defective virus, the lack of lamin A/C precluded accumulation of perinuclear virions and partially restored replication of this virus. These observations reveal different roles of specific lamins in HSV infection, suggesting that lamin A/C normally impedes viral nuclear egress and that US3 kinase helps alleviate this impediment, whereas lamin B1 is necessary for efficient viral replication, probably through its effects on many cellular signaling pathways. pUL31, the binding partner of pUL34, is also a substrate of pUS3. The N-terminus of pUL31 was found to be critical for the protein's normal function and contains multiple phosphorylation sites for US3 kinase. The phosphorylation was not essential for productive infection, but was necessary for optimal viral growth kinetics. Phosphorylation-deficient pUL31 caused pUL31/pUL34 complex aggregation as well as perinuclear virion accumulation, similar to the phenotype caused by abolishing US3 kinase activity. Mimicking phosphorylation of pUL31 by replacement of phosphorylated residues with glutamic acid largely restored the smooth distribution of pUL34/pUL31, and precluded the perinuclear virion herniations, regardless of US3 kinase activity. However, the pseudo-phosphorylated protein hindered the primary envelopment of capsids. These results indicate that pUL31 phosphorylation is a dynamic event, which mediates pUS3 regulatory functions in both primary envelopment of nucleocapsids and subsequent de-envelopment of perinuclear virions.

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.