scholarly journals Loss of endothelial cells in viral DNA-positive grafts after keratoplasty: a 2-year follow-up study

2020 ◽  
pp. bjophthalmol-2020-317629
Author(s):  
Jing-Hao Qu ◽  
Rong-Mei Peng ◽  
Ge-Ge Xiao ◽  
Hong-Qiang Qu ◽  
Ting Yu ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Loss Rate ◽  
Corneal Transplantation ◽  
Lamellar Keratoplasty ◽  
Viral Dna ◽  
Herpes Simplex Virus 1 ◽  
Varicella Zoster ◽  
Peking University ◽  
Simplex Virus

BackgroundTo compare endothelial loss between recipients who received viral DNA-positive grafts and controls 2 years after corneal transplantation.MethodsWe retrospectively analysed the clinical data and endothelial cell density of recipients of viral DNA-positive grafts and age-, sex-, aetiology- and operation-matched controls from April 2017 to July 2019 at the Peking University Third Hospital, Beijing, China.ResultsA total of 23/942 (2.44%) donor corneal buttons tested virus-positive by real-time PCR. A total of 27 recipients (except for 2 recipients) of viral DNA-positive grafts and 48 recipients of viral DNA-negative grafts were included in this study. Recipients of viral DNA-positive grafts had a higher endothelial cell (EC) loss rate post-penetrating keratoplasty and post-descemet stripping automated endothelial keratoplasty (p<0.05), but post-deep lamellar keratoplasty, the EC loss rate was similar to that of the controls. Recipients of herpes simplex virus-1-, cytomegalovirus- and varicella-zoster virus-positive grafts all had a higher EC loss rate than the controls during the 12- and 24-month follow-up periods (p<0.05).ConclusionWe inferred that viruses might be hidden in corneal grafts and mainly incubate in the corneal endothelium. Viral DNA-positive grafts do not need to be replaced immediately and can be followed up for a long time.

scholarly journals Engagement of the Lysine-Specific Demethylase/HDAC1/CoREST/REST Complex by Herpes Simplex Virus 1

2009 ◽  
Vol 83 (9) ◽  
pp. 4376-4385 ◽  
Author(s):  
Haidong Gu ◽  
Bernard Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nuclear Bodies ◽  
Wild Type Virus ◽  
Viral Dna ◽  
Herpes Simplex Virus 1 ◽  
Lysine Specific Demethylase ◽  
Repressor Complex ◽  
Infected Cells ◽  
Simplex Virus

ABSTRACT Among the early events in herpes simplex virus 1 replication are localization of ICP0 in ND10 bodies and accumulation of viral DNA-protein complexes in structures abutting ND10. ICP0 degrades components of ND10 and blocks silencing of viral DNA, achieving the latter by dislodging HDAC1 or -2 from the lysine-specific demethylase 1 (LSD1)/CoREST/REST repressor complex. The role of this process is apparent from the observation that a dominant-negative CoREST protein compensates for the absence of ICP0 in a cell-dependent fashion. HDAC1 or -2 and the CoREST/REST complex are independently translocated to the nucleus once viral DNA synthesis begins. The focus of this report is twofold. First, we report that in infected cells, LSD1, a key component of the repressor complex, is partially degraded or remains stably associated with CoREST and is ultimately also translocated, in part, to the cytoplasm. Second, we examined the distribution of the components of the repressor complex and ICP8 early in infection in wild-type-virus- and ICP0 mutant virus-infected cells. The repressor component and ultimately ICP8 localize in structures that abut the ND10 nuclear bodies. There is no evidence that the two compartments fuse. We propose that ICP0 must dynamically interact with both compartments in order to accomplish its functions of degrading PML and SP100 and suppressing silencing of viral DNA through its interactions with CoREST. In turn, the remodeling of the viral DNA-protein complex enables recruitment of ICP8 and initiation of formation of replication compartments.

scholarly journals Varicella-Zoster Virus and Herpes Simplex Virus 1 Differentially Modulate NKG2D Ligand Expression during Productive Infection

2015 ◽  
Vol 89 (15) ◽  
pp. 7932-7943 ◽  
Author(s):  
Tessa M. Campbell ◽  
Brian P. McSharry ◽  
Megan Steain ◽  
Barry Slobedman ◽  
Allison Abendroth
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Cell Activity ◽  
Nkg2d Ligand ◽  
Nk Cell Activity ◽  
Herpes Simplex Virus 1 ◽  
Varicella Zoster ◽  
Ligand Expression ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTNatural killer (NK) cell-deficient patients are particularly susceptible to severe infection with herpesviruses, especially varicella-zoster virus (VZV) and herpes simplex virus 1 (HSV-1). The critical role that NK cells play in controlling these infections denotes an intricate struggle for dominance between virus and NK cell antiviral immunity; however, research in this area has remained surprisingly limited. Our study addressed this absence of knowledge and found that infection with VZV was not associated with enhanced NK cell activation, suggesting that the virus uses specific mechanisms to limit NK cell activity. Analysis of viral regulation of ligands for NKG2D, a potent activating receptor ubiquitously expressed on NK cells, revealed that VZV differentially modulates expression of the NKG2D ligands MICA, ULBP2, and ULBP3 by upregulating MICA expression while reducing ULBP2 and ULBP3 expression on the surface of infected cells. Despite being closely related to VZV, infection with HSV-1 produced a remarkably different effect on NKG2D ligand expression. A significant decrease in MICA, ULBP2, and ULBP3 was observed with HSV-1 infection at a total cellular protein level, as well as on the cell surface. We also demonstrate that HSV-1 differentially regulates expression of an additional NKG2D ligand, ULBP1, by reducing cell surface expression while total protein levels are unchanged. Our findings illustrate both a striking point of difference between two closely related alphaherpesviruses, as well as suggest a powerful capacity for VZV and HSV-1 to evade antiviral NK cell activity through novel modulation of NKG2D ligand expression.IMPORTANCEPatients with deficiencies in NK cell function experience an extreme susceptibility to infection with herpesviruses, in particular, VZV and HSV-1. Despite this striking correlation, research into understanding how these two alphaherpesviruses interact with NK cells is surprisingly limited. Through examination of viral regulation of ligands to the activating NK cell receptor NKG2D, we reveal patterns of modulation by VZV, which were unexpectedly varied in response to regulation by HSV-1 infection. Our study begins to unravel the undoubtedly complex interactions that occur between NK cells and alphaherpesvirus infection by providing novel insights into how VZV and HSV-1 manipulate NKG2D ligand expression to modulate NK cell activity, while also illuminating a distinct variation between two closely related alphaherpesviruses.

scholarly journals Transient DNA Binding Induces RNA Polymerase II Compartmentalization During Herpesviral Infection Distinct From Phase Separation

2018 ◽  
Author(s):  
David T McSwiggen ◽  
Anders S Hansen ◽  
Hervé Marie-Nelly ◽  
Sheila Teves ◽  
Alec B Heckert ◽  
...  
Keyword(s):  
Phase Separation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Protein Interactions ◽  
Viral Dna ◽  
Herpes Simplex Virus 1 ◽  
Pol Ii ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Simplex Virus

SummaryDuring lytic infection, Herpes Simplex Virus 1 generates replication compartments (RCs) in host nuclei that efficiently recruit protein factors, including host RNA Polymerase II (Pol II). Pol II and other cellular factors form hubs in uninfected cells that are proposed to phase separate via multivalent protein-protein interactions mediated by their intrinsically disordered regions. Using a battery of live cell microscopic techniques, we show that although RCs superficially exhibit many characteristics of phase separation, the recruitment of Pol II instead derives from nonspecific interactions with the viral DNA. We find that the viral genome remains nucleosome-free, profoundly affecting the way Pol II explores RCs by causing it to repetitively visit nearby binding sites, thereby creating local Pol II accumulations. This mechanism, distinct from phase separation, allows viral DNA to outcompete host DNA for cellular proteins. Our work provides new insights into the strategies used to create local molecular hubs in cells.

scholarly journals The Therapeutic Effect of Corneal Transplantation for Refractory Pseudomonas Aeruginosa Corneal Ulcer

2019 ◽  
Author(s):  
Yan Li ◽  
Ting Wang ◽  
Qiang Wang ◽  
Shanhao Jiang ◽  
Xin Wang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Visual Acuity ◽  
Corneal Ulcer ◽  
Corneal Transplantation ◽  
Corneal Graft ◽  
Successful Outcome ◽  
Lamellar Keratoplasty ◽  
Corneal Transplant ◽  
Surgical Method

Abstract Purpose To observe the treatment outcome of corneal transplantation for advanced medically uncontrolled culture-proven pseudomonas aeruginosa corneal ulcer.Design Retrospective analysisSubjects and methods 26 patients (eyes) with refractory culture-positive pseudomonas aeruginosa corneal ulcer who failed to respond to drug therapy and underwent consecutive corneal transplant procedures in a hospital (2008.1-2018.8). Etiology, medical history, clinical features, surgical type, vision, recurrence, complications and treatment were recorded, and the relationship between postoperative recovery and selection of surgical method was analyzed.Results Of the 26 patients with pseudomonas aeruginosa corneal ulcer, 9 (34.6%) received penetrating keratoplasty (PKP) and 17 (65.4%) received lamellar keratoplasty (LKP). 22 patients (84.6%) obtained a successful outcome through one corneal transplantation. Of the 9 patients who received PKP, 1 patient having graft rejection 6 months after surgery (endothelial type) obtained successful outcome through adequate drug treatment., while 1 case received success by graft repair combined with amniotic membrane transplantation on the 5 months postoperatively for fungal corneal graft ulcer. In the 17 patients underwent LKP, 2 received a second successful lamellar corneal transplantation for corneal graft melting 2 months after the first surgery. In all the 26 patients, the corneal infection was effectively brought under control by corneal transplantation, and none of them had recurrent ulcers during at least 6months' follow-up. The visual acuity was significantly improved at the last follow-up compared with that before surgery. The postoperative visual acuity of patients underwent LKP was better than that of those who underwent PKP ( p =0.018).Conclusions Corneal transplantation can effectively treat refractory pseudomonas aeruginosa corneal ulcer worsening despite adequate medical treatment and improve eyesight. Compared with PKP, LKP can be the main surgical method to treat refractory pseudomonas aeruginosa corneal ulcer.

scholarly journals RNA Polymerase II Promoter-Proximal Pausing and Release to Elongation Are Key Steps Regulating Herpes Simplex Virus 1 Transcription

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Claire H. Birkenheuer ◽  
Joel D. Baines
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Rna Polymerase Ii ◽  
Viral Genome ◽  
Viral Dna ◽  
Herpes Simplex Virus 1 ◽  
Pol Ii ◽  
Late Genes ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (Pol II). Expression of viral immediate early (α) genes is followed sequentially by early (β), late (γ1), and true late (γ2) genes. We used precision nuclear run-on with deep sequencing to map and to quantify Pol II on the HSV-1(F) genome with single-nucleotide resolution. Approximately 30% of total Pol II relocated to viral genomes within 3 h postinfection (hpi), when it occupied genes of all temporal classes. At that time, Pol II on α genes accumulated most heavily at promoter-proximal pause (PPP) sites located ∼60 nucleotides downstream of the transcriptional start site, while β genes bore Pol II more evenly across gene bodies. At 6 hpi, Pol II increased on γ1 and γ2 genes while Pol II pausing remained prominent on α genes. At that time, average cytoplasmic mRNA expression from α and β genes decreased, relative to levels at 3 hpi, while γ1 relative expression increased slightly and γ2 expression increased more substantially. Cycloheximide treatment during the first 3 h reduced the amount of Pol II associated with the viral genome and confined most of the remaining Pol II to α gene PPP sites. Inhibition of both cyclin-dependent kinase 9 activity and viral DNA replication reduced Pol II on the viral genome and restricted much of the remaining Pol II to PPP sites. IMPORTANCE These data suggest that viral transcription is regulated not only by Pol II recruitment to viral genes but also by control of elongation into viral gene bodies. We provide a detailed map of Pol II occupancy on the HSV-1 genome that clarifies features of the viral transcriptome, including the first identification of Pol II PPP sites. The data indicate that Pol II is recruited to late genes early in infection. Comparing α and β gene occupancy at PPP sites and gene bodies suggests that Pol II is released more efficiently into the bodies of β genes than α genes at 3 hpi and that repression of α gene expression late in infection is mediated by prolonged promoter-proximal pausing. In addition, DNA replication is required to maintain full Pol II occupancy on viral DNA and to promote elongation on late genes later in infection.

scholarly journals Varicella-Zoster Virus (VZV) Glycoprotein E Is a Serological Antigen for Detection of Intrathecal Antibodies to VZV in Central Nervous System Infections, without Cross-Reaction to Herpes Simplex Virus 1

2011 ◽  
Vol 18 (8) ◽  
pp. 1336-1342 ◽  
Author(s):  
Anna Grahn ◽  
Marie Studahl ◽  
Staffan Nilsson ◽  
Elisabeth Thomsson ◽  
Malin Bäckström ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Igg Antibodies ◽  
Herpes Simplex Virus 1 ◽  
Glycoprotein E ◽  
Varicella Zoster ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTHerpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) cause serious central nervous system (CNS) diseases that are diagnosed with PCR using samples of cerebrospinal fluid (CSF) and, during later stages of such infections, with assays of intrathecal IgG antibody production. However, serological diagnoses have been hampered by cross-reactions between HSV-1 and VZV IgG antibodies and are commonly reported in patients with herpes simplex encephalitis (HSE). In this study we have evaluated VZV glycoprotein E (gE) as a new antigen for serological diagnosis of VZV-induced CNS infections. Paired samples of CSF and serum from 29 patients with clinical diagnosis of VZV CNS infection (n= 15) or HSE (n= 14), all confirmed by PCR, were analyzed. VZV gE and whole VZV were compared as antigens in enzyme-linked immunosorbent assays (ELISAs) for serological assays in which the CSF/serum sample pairs were diluted to identical IgG concentrations. With the gE antigen, none of the HSE patients showed intrathecal IgG antibodies against VZV, compared to those shown by 11/14 patients using whole-VZV antigen (P< 0.001). In the patients with VZV infections, significantly higher CSF/serum optical density (OD) ratios were found in the VZV patients using the VZV gE antigen compared to those found using the whole-VZV antigen (P= 0.001). These results show that gE is a sensitive antigen for serological diagnosis of VZV infections in the CNS and that this antigen was devoid of cross-reactivity to HSV-1 IgG in patients with HSE. We therefore propose that VZV gE can be used for serological discrimination of CNS infections caused by VZV and HSV-1.

Endothelial cell density after posterior lamellar keratoplasty (Melles techniques): 3 years follow-up

2004 ◽  
Vol 138 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Bart Van Dooren ◽  
Paul G.H. Mulder ◽  
Carla P. Nieuwendaal ◽  
W.H. Beekhuis ◽  
Gerrit R.J. Melles
Keyword(s):  
Endothelial Cell ◽  
Cell Density ◽  
Endothelial Cell Density ◽  
Lamellar Keratoplasty ◽  
Posterior Lamellar Keratoplasty

scholarly journals The Herpes Simplex Virus 1 UL34 Protein Interacts with a Cytoplasmic Dynein Intermediate Chain and Targets Nuclear Membrane

2000 ◽  
Vol 74 (3) ◽  
pp. 1355-1363 ◽  
Author(s):  
Guo-Jie Ye ◽  
Kevin T. Vaughan ◽  
Richard B. Vallee ◽  
Bernard Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nuclear Membrane ◽  
Viral Proteins ◽  
Cytoplasmic Dynein ◽  
Dependent Manner ◽  
Viral Dna ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Intermediate Chain

ABSTRACT To express the function encoded in its genome, the herpes simplex virus 1 capsid-tegument structure released by deenvelopment during entry into cells must be transported retrograde to the nuclear pore where viral DNA is released into the nucleus. This path is essential in the case of virus entering axons of dorsal root ganglia. The objective of the study was to identify the viral proteins that may be involved in the transport. We report the following findings. (i) The neuronal isoform of the intermediate chain (IC-1a) of the dynein complex pulled down, from lysates of [35S]methionine-labeled infected cells, two viral proteins identified as the products of UL34 and UL31 open reading frames, respectively. UL34 protein is a virion protein associated with cellular membranes and phosphorylated by the viral kinase US3. UL31 protein is a largely insoluble, evenly dispersed nuclear phosphoprotein required for optimal processing and packaging of viral DNA into preformed capsids. Reciprocal pulldown experiments verified the interaction of IC-1a and UL34 protein. In similar experiments, UL34 protein was found to interact with UL31 protein and the major capsid protein ICP5. (ii) To determine whether UL34 protein is transported to the nuclear membrane, a requirement if it is involved in transport, the UL34 protein was inserted into a baculovirus vector under the cytomegalovirus major early promoter. Cells infected with the recombinant baculovirus expressed UL34 protein in a dose-dependent manner, and the UL34 protein localized primarily in the nuclear membrane. An unexpected finding was that UL34-expressing cells showed a dissociation of the inner and outer nuclear membranes reminiscent of the morphologic changes seen in cells productively infected with herpes simplex virus 1. UL34, like many other viral proteins, may have multiple functions expressed both early and late in infection.

scholarly journals Deep Anterior Lamellar Keratoplasty followed by Toric Lens Implantation for the Treatment of Concomitant Anterior Stromal Diseases and Cataract

2017 ◽  
Vol 1 (1) ◽  
pp. oapoc.0000008 ◽  
Author(s):  
Vincenzo Scorcia ◽  
Andrea Lucisano ◽  
Vincenzo Savoca Corona ◽  
Valentina De Luca ◽  
Adriano Carnevali ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Endothelial Cell ◽  
Cataract Surgery ◽  
Lamellar Keratoplasty ◽  
Deep Anterior Lamellar Keratoplasty ◽  
Toric Iol ◽  
Iol Implantation ◽  
Anterior Lamellar Keratoplasty ◽  
Topographic Astigmatism

Purpose To evaluate the outcomes of deep anterior lamellar keratoplasty (DALK) followed by phacoemulsification and toric intraocular lens (IOL) implantation for the treatment of concomitant stromal disease and cataract. Methods In this retrospective non-comparative interventional case series, ten eyes affected by stromal disease and cataract underwent DALK followed by phacoemulsification with toric IOL implantation after a minimum period of 5 months from complete suture removal. In each case, topographic astigmatism, refraction, visual acuity, and endothelial cell density were recorded before DALK and 1, 6, and 12 months after cataract surgery. In addition, IOL rotation was evaluated using anterior segment optical coherence tomography. Results Big-bubble DALK was performed in all eyes but one that received manual dissection. Topographic astigmatism averaged 5.6 ± 2.2 diopters (D) after suture removal; refractive astigmatism decreased to 0.55 ± 0.61 D as early as one month after cataract surgery and did not change substantially throughout the follow-up period. In all patients, one month after phacoemulsification uncorrected and best spectacle-corrected visual acuity were, respectively, ≥20/40 and ≥20/25 with a residual spherical equivalent of 0.00 ± 0.84 D. At the latest follow-up visit, in all cases the IOL rotation was ≤5 degrees from the intended position and the endothelial cell loss within 8.5%. No complications were recorded. Conclusions DALK followed by phacoemulsification with toric IOL implantation optimizes visual and refractive outcomes in patients with concomitant stromal disease and cataract. In comparison with a combined procedure, the sequential approach offers better predictability of the postoperative refraction in the absence of an increased risk of complications.

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