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herpesvirus respiratory infections in immunocompromised patients: epidemiology, management, and outcomes.among immunocompromised individuals, members of the human herpesviridae family are frequently encountered pathogens. cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus, epstein-barr virus, and human herpesvirus-6, -7, and -8 all establish latency after infection and can reactivate during periods of immunosuppression, leading to both direct and indirect adverse effects on the host including severe organ dysfunction as well as allograft rejection and loss after transplantation. ...201627486740
an overview of infectious complications after allogeneic hematopoietic stem cell transplantation.infections are the most common and significant cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-hsct). the presence of neutropenia and mucosal damage are the leading risk factors in the early pre-engraftment phase. in the early post-engraftment phase, graft versus host disease (gvhd) induced infection risk is increased in addition to catheter related infections. in the late phase, in which reconstitution of cellular and humoral immunity continues, a ...201627344206
herpesvirus infections and childhood arterial ischemic stroke: results of the vips study.epidemiological studies demonstrate that childhood infections, including varicella zoster virus, are associated with an increased risk of arterial ischemic stroke (ais). other herpesviruses have been linked to childhood ais in case reports. we sought to determine whether herpesvirus infections, which are potentially treatable, increase the risk of childhood ais.201626813104
epstein-barr virus: the path from latent to productive infection.the intrinsic properties of different viruses have driven their study. for example, the capacity for efficient productive infection of cultured cells by herpes simplex virus 1 has made it a paradigm for this mode of infection for herpesviruses in general. epstein-barr virus, another herpesvirus, has two properties that have driven its study: it causes human cancers, and it exhibits a tractable transition from its latent to its productive cycle in cell culture. here, we review our understanding o ...201627578440
synthesis and antiviral activity of 1-(1,3-disubstitutedimidazolidyn-2-ylidene)-3-ethoxycarbonylmethylurea derivatives.novel 1-(1,3-disubstituted-imidazolidyn-2-ylidene)-3-ethoxycarbonylmethylurea derivatives (3a-3j) were obtained from appropriate 1-aryl-3-arylsulfonyl-1h-imidazolidine-2-imines (1a-1j) and ethyl isocyanatoacetate (2), which were subjected to condensation. seven compounds were tested for their antiviral activity against hsv-1 and cvb3 viruses. among the tested compounds, 3c was found to be active against hsv-1, proving that 4-methoxy substituent as r and 4-methyl substituent as r1 are most benefi ...201625798689
fatal neonatal herpes simplex infection likely from unrecognized breast lesions.type 1 herpes simplex virus (hsv-1) is very prevalent yet in rare circumstances can lead to fatal neonatal disease. genital acquisition of type 2 hsv is the usual mode for neonatal herpes, but hsv-1 transmission by genital or extragenital means may result in greater mortality rates. a very rare scenario is presented in which the mode of transmission was likely through breast lesions. the lesions were seen by nurses as well as the lactation consultant and obstetrician in the hospital after delive ...201626185119
large amounts of reactivated virus in tears precedes recurrent herpes stromal keratitis in stressed rabbits latently infected with herpes simplex virus.recurrent herpetic stromal keratitis (rhsk), due to an immune response to reactivation of herpes simplex virus (hsv-1), can cause corneal blindness. the development of therapeutic interventions such as drugs and vaccines to decrease rhsk have been hampered by the lack of a small and reliable animal model in which rhsk occurs at a high frequency during hsv-1 latency. the aim of this study is to develop a rabbit model of rhsk in which stress from elevated temperatures increases the frequency of hs ...201625859798
[kikuchi-fujimoto disease prior to childhood-systemic lupus erythematosus diagnosis].kikuchi-fujimoto disease (kfd) is a self-limiting histiocytic necrotizing lymphadenitis of unknown origin. of note, kfd was infrequently reported in adult systemic lupus erythematosus (sle), with rare occurrence in childhood-sle (c-sle) patients. to our knowledge, the prevalence of kfd in the paediatric lupus population was not studied. therefore, in a period of 29 consecutive years, 5,682 patients were followed at our institution and 289 (5%) met the american college of rheumatology classificat ...201625627306
antimicrobial photodynamic therapy to treat chemotherapy-induced oral lesions: report of three cases.the development of angular cheilitis and the reactivation of herpes simplex virus, could be related to a decrease in the resistance of the immune system in the infected host, being common in cancer patients receiving antineoplastic chemotherapy. the objective of the present manuscript is to report antimicrobial photodynamic therapy as a treatment of infected oral lesions of patients submitted to chemotherapy.201626222604
pediatric medulloblastoma xenografts including molecular subgroup 3 and cd133+ and cd15+ cells are sensitive to killing by oncolytic herpes simplex viruses.childhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (cscs), marked by the surface protein cd133 or cd15. brain tumors characteristically con ...201626188016
chronic herpes simplex type-1 encephalitis with intractable epilepsy in an immunosuppressed patient.chronic herpes simplex virus type-1 encephalitis (hse-1) is uncommon. past reports focused on its association with prior documented acute infection. here, we describe a patient with increasingly intractable epilepsy from chronic hse-1 reactivation without history of acute central nervous system infection.201626187268
increased neurovirulence and reactivation of the herpes simplex virus type 1 latency-associated transcript (lat)-negative mutant dlat2903 with a disrupted lat mir-h2.at least six micrornas (mirnas) appear to be encoded by the latency-associated transcript (lat) of herpes simplex virus type 1 (hsv-1). the gene for icp0, an important immediate early (ie) viral protein, is anti-sense to, and overlaps with, the region of lat from which mirna h2 (mir-h2) is derived. we recently reported that a mutant (mck-δh2) disrupted for mir-h2 on the wild-type hsv-1 strain mckrae genomic background has increased icp0 expression, increased neurovirulence, and slightly more rap ...201626069184
history and genomic sequence analysis of the herpes simplex virus 1 kos and kos1.1 sub-strains.a collection of genomic dna sequences of herpes simplex virus (hsv) strains has been defined and analyzed, and some information is available about genomic stability upon limited passage of viruses in culture. the nature of genomic change upon extensive laboratory passage remains to be determined. in this report we review the history of the hsv-1 kos laboratory strain and the related kos1.1 laboratory sub-strain, also called kos (m), and determine the complete genomic sequence of an early passage ...201626547038
ubiquitin-specific protease 9x in host cells interacts with herpes simplex virus 1 icp0.herpes simplex virus 1 (hsv-1) expresses infected cell protein 0 (icp0), a multi-functional protein with e3 ubiquitin ligase activity and a critical regulator of the viral life cycle. to obtain novel insights into the molecular mechanism by which icp0 regulates hsv-1 replication, we analyzed hep-2 cells infected with hsv-1 by tandem affinity purification and mass spectrometry-based proteomics. this screen identified 50 host-cell proteins that potentially interact with icp0, including ubiquitin-s ...201626596467
confocal microscopic analysis of a rabbit eye model of high-incidence recurrent herpes stromal keratitis.using cjlat, a chimeric herpes simplex virus (hsv-1) that produces a high incidence of herpes stromal keratitis (hsk) in latently infected rabbits, and in vivo confocal microscopy (cm), we characterized the cellular events that precede the development of hsk.201626555580
herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection.herpes simplex virus (hsv) was originally implicated in the aetiology of cervical cancer, and although high-risk human papillomavirus (hpv) is now the accepted causative agent, the epidemiological link between hsv and hpv-associated cancers persists. the annexin a2 heterotetramer (a2t) has been shown to mediate infectious hpv type 16 (hpv16) uptake by human keratinocytes, and secretory leukocyte protease inhibitor (slpi), an endogenous a2t ligand, inhibits hpv16 uptake and infection. interesting ...201626555393
herpes simplex encephalitis in a captive black howler monkey (alouatta caraya).an 18-month-old captive black howler monkey (alouatta caraya) died after a 3-day history of neurologic signs. gross findings at autopsy were limited to bloody, yellow, and foul-smelling intestinal contents. histologically, there was extensive necrotizing meningoencephalitis predominantly in both cerebral hemispheres, and lymphohistiocytic, neutrophilic infiltrate expanded the subarachnoid and virchow-robbin space. in the most severely affected regions, neurons contained eosinophilic intranuclear ...201626699521
analyses of herpes simplex virus type 1 latency and reactivation at the single cell level using fluorescent reporter mice.herpes simplex virus type 1 (hsv-1) establishes a latent infection in sensory neurons from which the virus can periodically reactivate. whilst latency establishment is thought to result from a failure to express immediate-early genes, we have previously shown that subpopulations of the latent neuronal reservoir have undergone lytic promoter activation prior to latency establishment. in the present study, we have investigated the biological properties of such latently infected neuronal subpopulat ...201626694770
photo inactivation of virus particles in microfluidic capillary systems.it has long been established that uvc light is a very effective method for inactivating pathogens in a fluid, yet the application of uvc irradiation to modern biotechnological processes is limited by the intrinsic short penetration distance of uvc light in optically dense protein solutions. this experimental and numerical study establishes that irradiating a fluid flowing continuously in a microfluidic capillary system, in which the diameter of the capillary is tuned to the depth of penetration ...201626694540
anti-n-methyl-d-aspartate receptor encephalitis in a young child with histological evidence on brain biopsy of coexistent herpes simplex virus type 1 infection.we report a 3-year-old boy with anti-n-methyl-d-aspartate receptor encephalitis with a typical syndrome of movement disorder and encephalopathy and evidence of herpes simplex virus (hsv) type 1 infection on brain biopsy. hsv type 1 infection and anti-n-methyl-d-aspartate receptor encephalitis are temporally linked in some cases: this case suggests that prodromal hsv type-1 infection may be clinically subtle and easily missed.201626658379
synthetic stigmastanes with dual antiherpetic and immunomodulating activities inhibit erk and akt signaling pathways without binding to glucocorticoid receptors.we have previously shown that some synthetic hydroxylated stigmastanes derived from plant sterols inhibit in vitro hsv-1 replication in ocular cell lines and decrease cytokine production in stimulated macrophages, suggesting that these steroids might combine antiviral and immunomodulating properties. in this paper we report the synthesis of some analogs fluorinated at c-6 in order to study the effect of this modification on bioactivity.201626518349
herpes simplex virus type 2 encephalitis as a cause of ischemic stroke: case report and systematic review of the literature.our objective is to describe a patient who developed an ischemic stroke as a complication of herpes simplex virus type 2 (hsv-2) encephalitis and to review the literature.201626542825
inhibition of herpes simplex virus type 1 by the cdk6 inhibitor pd-0332991 (palbociclib) through the control of samhd1.sterile α motif and histidine-aspartate domain-containing protein 1 (samhd1) has been shown to restrict retroviruses and dna viruses by decreasing the pool of intracellular deoxynucleotides. in turn, samhd1 is controlled by cyclin-dependent kinases (cdk) that regulate the cell cycle and cell proliferation. here, we explore the effect of cdk6 inhibitors on the replication of herpes simplex virus type 1 (hsv-1) in primary monocyte-derived macrophages (mdm).201626542306
prophylactic valacyclovir to prevent outbreaks of primary herpes gladiatorum at a 28-day wrestling camp: a 10-year review.to determine efficacy of using oral antiviral medication to reduce herpes gladiatorum (hg) at summer high-school wrestling camps.201626540599
quantitative trait locus based virulence determinant mapping of the hsv-1 genome in murine ocular infection: genes involved in viral regulatory and innate immune networks contribute to virulence.herpes simplex virus type 1 causes mucocutaneous lesions, and is the leading cause of infectious blindness in the united states. animal studies have shown that the severity of hsv-1 ocular disease is influenced by three main factors; innate immunity, host immune response and viral strain. we previously showed that mixed infection with two avirulent hsv-1 strains (od4 and cj994) resulted in recombinants that exhibit a range of disease phenotypes from severe to avirulent, suggesting epistatic inte ...201626962864
silencing status epilepticus-induced bdnf expression with herpes simplex virus type-1 based amplicon vectors.brain-derived neurotrophic factor (bdnf) has been found to produce pro- but also anti-epileptic effects. thus, its validity as a therapeutic target must be verified using advanced tools designed to block or to enhance its signal. the aim of this study was to develop tools to silence the bdnf signal. we generated herpes simplex virus type 1 (hsv-1) derived amplicon vectors, i.e. viral particles containing a genome of 152 kb constituted of concatameric repetitions of an expression cassette, enabli ...201626954758
evasion of host antiviral innate immunity by hsv-1, an update.herpes simplex virus type 1 (hsv-1) infection triggers a rapid induction of host innate immune responses. the type i interferon (ifn) signal pathway is a central aspect of host defense which induces a wide range of antiviral proteins to control infection of incoming pathogens. in some cases, viral invasion also induces dna damage response, autophagy, endoplasmic reticulum stress, cytoplasmic stress granules and other innate immune responses, which in turn affect viral infection. however, hsv-1 h ...201626952111
viral forensic genomics reveals the relatedness of classic herpes simplex virus strains kos, kos63, and kos79.herpes simplex virus 1 (hsv-1) is a widespread global pathogen, of which the strain kos is one of the most extensively studied. previous sequence studies revealed that kos does not cluster with other strains of north american geographic origin, but instead clustered with asian strains. we sequenced a historical isolate of the original kos strain, called kos63, along with a separately isolated strain attributed to the same source individual, termed kos79. genomic analyses revealed that kos63 clos ...201626950505
uv-inactivated hsv-1 potently activates nk cell killing of leukemic cells.herein we demonstrate that oncolytic herpes simplex virus-1 (hsv-1) potently activates human peripheral blood mononuclear cells (pbmcs) to lyse leukemic cell lines and primary acute myeloid leukemia samples, but not healthy allogeneic lymphocytes. intriguingly, we found that uv light-inactivated hsv-1 (uv-hsv-1) is equally effective in promoting pbmc cytolysis of leukemic cells and is 1000- to 10 000-fold more potent at stimulating innate antileukemic responses than uv-inactivated cytomegaloviru ...201626941401
lychee flower extract inhibits proliferation and viral replication of hsv-1-infected corneal epithelial cells.herpes simplex virus type i (hsv-1) is capable of causing a wide array of human ocular diseases. herpes simplex virus keratitis (hsk)-induced cytopathogenicity together with the chronic immune-inflammatory reaction can trigger stromal scarring, thinning, and neovascularization which may lead to permanent vision impairment. lychee flower extract (lfe) is known for its antioxidant and anti-inflammatory effects. therefore, in this study, we investigated the mechanism of the statens seruminstitut ra ...201626937165
gd-independent superinfection exclusion of alphaherpesviruses.many viruses have the capacity to prevent a cell from being infected by a second virus, often termed superinfection exclusion. alphaherpesviruses, including the human pathogen herpes simplex virus 1 (hsv-1) and the animal herpesvirus pseudorabies virus (prv), encode a membrane-bound glycoprotein, gd, that can interfere with subsequent virion entry. we sought to characterize the timing and mechanism of superinfection exclusion during hsv-1 and prv infection. to this end, we utilized recombinant v ...201626842480
the herpes simplex virus latency-associated transcript gene is associated with a broader repertoire of virus-specific exhausted cd8+ t cells retained within the trigeminal ganglia of latently infected hla transgenic rabbits.persistent pathogens, such as herpes simplex virus 1 (hsv-1), have evolved a variety of immune evasion strategies to avoid being detected and destroyed by the host's immune system. a dynamic cross talk appears to occur between the hsv-1 latency-associated transcript (lat), the only viral gene that is abundantly transcribed during latency, and the cd8(+)t cells that reside in hsv-1 latently infected human and rabbit trigeminal ganglia (tg). the reactivation phenotype of tg that are latently infec ...201626842468
two modes of the axonal interferon response limit alphaherpesvirus neuroinvasion.infection by alphaherpesviruses, including herpes simplex virus (hsv) and pseudorabies virus (prv), typically begins at epithelial surfaces and continues into the peripheral nervous system (pns). inflammatory responses are induced at the infected peripheral site prior to invasion of the pns. when the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (ifns). the fundamental question is how do pns cell bodies res ...201626838720
protective effect of amyloid-β peptides against herpes simplex virus-1 infection in a neuronal cell culture model.senile amyloid plaques are one of the main hallmarks of alzheimer's disease (ad). they correspond to insoluble deposits of amyloid-β peptides (aβ) and are responsible for the inflammatory response and neurodegeneration that lead to loss of memory. recent data suggest that aβ possess antimicrobial and anti-viral activity in vitro. here, we have used cocultures of neuroglioma (h4) and glioblastoma (u118-mg) cells as a minimal in vitro model to investigate whether aβ is produced by neuroglioma cell ...201626836158
expression and immunogenicity of recombinant glycoprotein d of herpes simplex virus 1 in drosophila s2 cells.herpes simplex virus type 1 (hsv-1) is responsible for cold sores in the general population, but also contributes to the development of other more serious diseases in some circumstances. the viral glycoprotein d (gd) is essential for virus entry into host cells. in the present study, the drosophila melanogaster schneider 2 (s2) expression system (des) was evaluated for the expression of recombinant gd1. the dna sequences encoding the full-length gd1 (369aa, flgd1) and a truncated gd1 form corres ...201626835587
mir-h28 and mir-h29 expressed late in productive infection are exported and restrict hsv-1 replication and spread in recipient cells.we report on the properties and function of two herpes simplex virus-1 (hsv-1) micrornas (mirnas) designated "mir-h28" and "mir-h29." both mirnas accumulate late in productive infection at a time when, for the most part, viral dna and proteins have been made. ectopic expression of mirna mimics in human cells before infection reduced the accumulation of viral mrnas and proteins, reduced plaque sizes, and at vey low multiplicities of infection reduced viral yields. the specificity of the mirna mim ...201626831114
ifn-γ primes keratinocytes for hsv-1-induced inflammasome activation.inflammasomes are immune complexes that induce an inflammatory response upon sensing of different stress signals. this effect is mainly mediated by activation and secretion of the proinflammatory cytokines proil-1β and -18. here we report that infection of human primary keratinocytes with the double-stranded dna viruses modified vaccinia virus ankara (mva) or herpes simplex virus type 1 (hsv-1)-induced secretion of mature il-1β and -18. this secretion was dependent on several inflammasome comple ...201626739094
cellular transcriptional coactivator ranbp10 and herpes simplex virus 1 icp0 interact and synergistically promote viral gene expression and replication.to investigate the molecular mechanism(s) by which herpes simplex virus 1 (hsv-1) regulatory protein icp0 promotes viral gene expression and replication, we screened cells overexpressing icp0 for icp0-binding host cell proteins. tandem affinity purification of transiently expressed icp0 coupled with mass spectrometry-based proteomics technology and subsequent analyses showed that icp0 interacted with cell protein ranbp10, a known transcriptional coactivator, in hsv-1-infected cells. knockdown of ...201626739050
th2 biased upper airway inflammation is associated with an impaired response to viral infection with herpes simplex virus 1.we aimed to elucidate possible differences in antiviral defense in chronic rhinosinusitis with nasal polyps (crswnp) mucosal tissue compared to healthy mucosal tissue (hmt) upon herpes simplex virus 1 (hsv1) exposure.201626702454
inflammatory and non-inflammatory breast cancer: a potential role for detection of multiple viral dnas in disease progression.inflammatory breast cancer (ibc) is the most lethal form of breast cancer. multiple viral infections in ibc tissues were found to be associated with disease pathogenesis.201626508152
detection of virus in csf from the cases with meningoencephalitis by next-generation sequencing.we screened for viral dna in cerebrospinal fluid samples using next-generation sequencing (ngs) technology to diagnose cns viral infections. we collected csf samples from four cases with clinically suspected viral meningoencephalitis. dna extracted from the samples was analyzed with ngs, and the results were further validated using pcr. herpes simplex virus 1 (hsv-1) was detected in the csf of two patients, hsv-2 and human herpes virus type 3 (hhv-3, vzv) in the csf of two other patients separat ...201626506841
reactivation of hsv-1 following explant of tree shrew brain.herpes simplex virus type i (hsv-1) latently infects peripheral nervous system (pns) sensory neurons, and its reactivation leads to recurring cold sores. the reactivated hsv-1 can travel retrograde from the pns into the central nervous system (cns) and is known to be causative of herpes simplex viral encephalitis. hsv-1 infection in the pns is well documented, but little is known on the fate of hsv-1 once it enters the cns. in the murine model, hsv-1 genome persists in the cns once infected thro ...201626501779
calcium spirulan derived from spirulina platensis inhibits herpes simplex virus 1 attachment to human keratinocytes and protects against herpes labialis.chronic infections with herpes simplex virus (hsv) type 1 are highly prevalent in populations worldwide and cause recurrent oral lesions in up to 40% of infected subjects.201626341274
genome-wide lentiviral shrna screen identifies serine/arginine-rich splicing factor 2 as a determinant of oncolytic virus activity in breast cancer cells.oncolytic human herpes simplex virus type 1 (hsv-1) shows promising treatment efficacy in late-stage clinical trials. the anticancer activity of oncolytic viruses relies on deregulated pathways in cancer cells, which make them permissive to oncolysis. to identify pathways that restrict hsv-1 km100-mediated oncolysis, this study used a pooled genome-wide short hairpin rna library and found that depletion of the splicing factor arginine-rich splicing factor 2 (srsf2) leads to enhanced cytotoxicity ...201626257065
database on natural polymorphisms and resistance-related non-synonymous mutations in thymidine kinase and dna polymerase genes of herpes simplex virus types 1 and 2.the use of genotypic resistance testing of herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) is increasing because the rapid availability of results significantly improves the treatment of severe infections, especially in immunocompromised patients. however, an essential precondition is a broad knowledge of natural polymorphisms and resistance-associated mutations in the thymidine kinase (tk) and dna polymerase (pol) genes, of which the dna polymerase (pol) enzyme is targeted by the highly ef ...201626433780
locked-in-like fulminant infantile guillain-barré syndrome associated with herpes simplex virus 1 infection.guillain-barré syndrome (gbs) may rarely manifest as a peripheral locked-in syndrome.201626372816
prior corneal scarification and injection of immune serum are not required before ocular hsv-1 infection for uv-b-induced virus reactivation and recurrent herpetic corneal disease in latently infected mice.blinding ocular herpetic disease in humans is due to spontaneous reactivation of herpes simplex virus type 1 (hsv-1) from latency, rather than to primary acute infection. mice latently infected with hsv-1 undergo little or no in vivo spontaneous reactivation with accompanying virus shedding in tears. hsv-1 reactivation can be induced in latently infected mice by several in vivo procedures, with uv-b-induced reactivation being one commonly used method. in the uv-b model, corneas are scarified (li ...201626398722
pentagalloylglucose blocks the nuclear transport and the process of nucleocapsid egress to inhibit hsv-1 infection.herpes simplex virus type 1 (hsv-1), a widespread virus, causes a variety of human viral diseases worldwide. the serious threat of drug-resistance highlights the extreme urgency to develop novel antiviral drugs with different mechanisms of action. pentagalloylglucose (pgg) is a natural polyphenolic compound with significant anti-hsv activity; however, the mechanisms underlying its antiviral activity need to be defined by further studies. in this study, we found that pgg treatment delays the nucl ...201626166506
lack of evidence for a role of hhv-6 in the pathogenesis of alzheimer's disease.alzheimer's disease (ad), the most common form of dementia worldwide, is associated with impairment in the mechanisms of the clearing of amyloid-β within a scenario of neuroinflammation. the etiopathogenesis of the ad is unclear, but a role for viral infection is suspected to play a role in initiating the disease. we recently described a positive correlation between high titers of hsv-1-specific antibodies (ab) and the volumes of brain regions typically affected in disease.201626444787
hsv-1 glycoproteins are delivered to virus assembly sites through dynamin-dependent endocytosis.herpes simplex virus-1 (hsv-1) is a large enveloped dna virus that belongs to the family of herpesviridae. it has been recently shown that the cytoplasmic membranes that wrap the newly assembled capsids are endocytic compartments derived from the plasma membrane. here, we show that dynamin-dependent endocytosis plays a major role in this process. dominant-negative dynamin and clathrin adaptor ap180 significantly decrease virus production. moreover, inhibitors targeting dynamin and clathrin lead ...201626459807
internal proteins of the procapsid and mature capsids of herpes simplex virus 1 mapped by bubblegram imaging.the herpes simplex virus 1 (hsv-1) capsid is a huge assembly, ∼1,250 å in diameter, and is composed of thousands of protein subunits with a combined mass of ∼200 mda, housing a 100-mda genome. first, a procapsid is formed through coassembly of the surface shell with an inner scaffolding shell; then the procapsid matures via a major structural transformation, triggered by limited proteolysis of the scaffolding proteins. three mature capsids are found in the nuclei of infected cells. a capsids are ...201626984725
novel role for protein inhibitor of activated stat 4 (pias4) in the restriction of herpes simplex virus 1 by the cellular intrinsic antiviral immune response.small ubiquitin-like modifier (sumo) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (hsv-1). despite characterization of the host factors that rely on sumoylation to exert their antiviral effects, the enzymes that mediate these sumoylation events remain to be defined. we show that unconjugated sumo levels are largely maintained throughout infection regardless of the presence of icp0, the hsv-1 sumo-targeted ubiquitin ligase. moreove ...201626937035
involvement of aberrant calcium signalling in herpetic neuralgia.alpha-herpesviruses, herpes simplex viruses (hsv) and varicella zoster virus (vzv), are pathogens of the peripheral nervous system. after primary infection, these viruses establish latency within sensory ganglia, while retaining the ability to reactivate. reactivation of vzv results in herpes zoster, a condition characterized by skin lesions that leads to post-herpetic neuralgia. recurrent reactivations of hsv, which cause mucocutaneous lesions, may also result in neuralgia. during reactivation ...201626684187
autophagy interaction with herpes simplex virus type-1 infection.more than 50% of the u.s. population is infected with herpes simplex virus type-i (hsv-1) and global infectious estimates are nearly 90%. hsv-1 is normally seen as a harmless virus but debilitating diseases can arise, including encephalitis and ocular diseases. hsv-1 is unique in that it can undermine host defenses and establish lifelong infection in neurons. viral reactivation from latency may allow hsv-1 to lay siege to the brain (herpes encephalitis). recent advances maintain that hsv-1 prote ...201626934628
prenylated phenyl polyketides and acylphloroglucinols from hypericum peplidifolium.in search for new or chemo-taxonomically relevant bioactive compounds from chemically unexplored hypericum species, four previously undescribed natural products, named peplidiforones a-d were isolated and characterized from hypericum peplidifolium a. rich., together with six known compounds. the structures of all compounds were elucidated by extensive 1d- and 2d-nmr experiments, high resolution mass spectrometric analyses (hr-ms), and by comparison with data reported in the literature. seven of ...201626880290
infected cell protein 0 functional domains and their coordination in herpes simplex virus replication.herpes simplex virus 1 (hsv-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. its unique life cycle requires a balanced "conquer and compromise" strategy to deal with the host anti-viral defenses. one of hsv-1 α (immediate early) gene products, infected cell protein 0 (icp0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. these pathways may locate in different cell compartments, which then migrate ...201626870669
extensive subunit contacts underpin herpesvirus capsid stability and interior-to-exterior allostery.the herpesvirus capsid is a complex protein assembly that includes hundreds of copies of four major subunits and lesser numbers of several minor proteins, all of which are essential for infectivity. cryo-electron microscopy is uniquely suited for studying interactions that govern the assembly and function of such large functional complexes. here we report two high-quality capsid structures, from human herpes simplex virus type 1 (hsv-1) and the animal pseudorabies virus (prv), imaged inside inta ...201627111889
redox imbalance and viral infections in neurodegenerative diseases.reactive oxygen species (ros) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. an imbalance in the production and elimination of ros is associated with human diseases including neurodegenerative disorders. in the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. it is known in literature that enhan ...201627110325
polyhydroxylated sulfated steroids derived from 5α-cholestanes as antiviral agents against herpes simplex virus.twelve polyhydroxylated sulfated steroids synthesized from a 5α-cholestane skeleton with different substitutions in c-2, c-3 and c-6 were evaluated for cytotoxicity and antiviral activity against herpes simplex virus (hsv) by a virus plaque reduction assay. four compounds elicited a selective inhibitory effect against hsv. the disodium salt of 2β,3α-dihydroxy-6e-hydroximine-5α-cholestane-2,3-disulfate, named compound 7, was the most effective inhibitor of hsv-1, hsv-2 and pseudorabies virus (prv ...201627101075
extended release of an anti-heparan sulfate peptide from a contact lens suppresses corneal herpes simplex virus-1 infection.to prolong the release of a heparan sulfate binding peptide, g2-c, using a commercially available contact lens as a delivery vehicle and to demonstrate the ability of the released peptide to block herpes simplex virus-1 (hsv-1) infection using in vitro, ex vivo, and in vivo models of corneal hsv-1 infection.201626780322
development of a multiplex real-time pcr for the simultaneous detection of herpes simplex and varicella zoster viruses in cerebrospinal fluid and lesion swab specimens.herpes simplex viruses (hsv) and varicella zoster virus (vzv) can have very similar and wide-ranging clinical presentations. rapid identification is necessary for timely antiviral therapy, especially with infections involving the central nervous system, neonates, and immunocompromised individuals. detection of hsv-1, hsv-2 and vzv was combined into one real-time pcr reaction utilizing hydrolysis probes. the assay was validated on the lightcycler(®) (roche) and applied biosystems 7500 real-time p ...201626711555
nectin-1 and hvem: cellular receptors for hsv-1 in skin. 201627031306
immunogenic cell death by oncolytic herpes simplex virus type 1 in squamous cell carcinoma cells.molecules essential for the induction of immunogenic cell death (icd) are called damage-associated molecular patterns (damps). the effects of oncolytic herpes simplex virus type 1 (hsv-1) on the production of damps were examined in squamous cell carcinoma (scc) cells. the cytopathic effects of hsv-1 rh2 were observed in mouse sccvii cells infected at a high multiplicity of infection (moi), and the amounts of viable cells were decreased. after being infected with rh2, atp and high mobility group ...201626987291
sumo ligase protein inhibitor of activated stat1 (pias1) is a constituent promyelocytic leukemia nuclear body protein that contributes to the intrinsic antiviral immune response to herpes simplex virus 1.aspects of intrinsic antiviral immunity are mediated by promyelocytic leukemia nuclear body (pml-nb) constituent proteins. during herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. central to the execution of this particular antiviral response is the small ubiquitin-like modifier (sumo) signaling pathway. however, the participating sumoylation enzymes are not fully ch ...201627099310
innate defense mechanisms against hsv-1 infection in the target tissues, skin and brain.herpes simplex virus type 1 (hsv-1) initiates productive infection in mucocutaneous tissues to cause cold sores and establishes latent infection in the trigeminal ganglia. under certain circumstances, hsv-1 may cause encephalitis. here, we compared host innate defenses against hsv-1 in the two clinically relevant tissues, skin and brain, using a unique ex vivo system of organ culture. upon hsv-1 infection and spread, apoptosis induction was observed in the skin, but not in brain tissues. while t ...201627098517
effects of rna interference therapy against herpes simplex virus type 1 encephalitis.herpetic encephalitis (hse) is caused mainly by herpes simplex virus type 1 (hsv-1) with an annual incidence of 1-4 cases/million inhabitants. currently, hse treatment faces difficulties such as the use of antivirals with elevated toxicity, metabolic side effects and hsv-1 resistance. an alternative to antivirals is the use of small interfering rna (sirna) as a viral replication inhibitor. in this work, sirna targeting the ul-39 region was evaluated for hse treatment in vivo.201626669609
evaluation of an automated chemiluminescent immunoassay in typing detection of igg antibodies against herpes simplex virus.herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) are common infectious agents worldwide and the primary infection of hsv remains a major problem in the pregnant women in china nowadays. at present, typing detection of hsv is mainly based on elisa in china.201626666528
abalone hemocyanin blocks the entry of herpes simplex virus 1 into cells: a potential new antiviral strategy.a marine-derived compound, abalone hemocyanin, from haliotis rubra was shown to have a unique mechanism of antiviral activity against herpes simplex virus 1 (hsv-1) infections. in vitro assays demonstrated the dose-dependent and inhibitory effect of purified hemocyanin against hsv-1 infection in vero cells with a 50% effective dose (ed50) of 40 to 50 nm and no significant toxicity. in addition, hemocyanin specifically inhibited viral attachment and entry by binding selectively to the viral surfa ...201626643336
a sting-dependent innate-sensing pathway mediates resistance to corneal hsv-1 infection via upregulation of the antiviral effector tetherin.type 1 interferons (ifns; ifnα/β) mediate immunological host resistance to numerous viral infections, including herpes simplex virus type 1 (hsv-1). the pathways responsible for ifnα/β signaling during the innate immune response to acute hsv-1 infection in the cornea are incompletely understood. using a murine ocular infection model, we hypothesized that the stimulator of ifn genes (sting) mediates resistance to hsv-1 infection at the ocular surface and preserves the structural integrity of this ...201626627457
talimogene laherparepvec: first global approval.talimogene laherparepvec (imlygic™) is an oncolytic viral therapy that is being developed by biovex (a subsidiary of amgen) for the intralesional treatment of various cancers, including malignant melanoma. talimogene laherparepvec is a genetically modified, live, attenuated, herpes simplex virus type 1 that is designed to promote an antitumour response through selective viral replication in tumour cells and stimulation of systemic antitumour immunity. in october 2015, talimogene laherparepvec wa ...201626620366
herpes simplex virus seroprevalence and seroconversion among active duty us air force members with hiv infection.herpes simplex virus (hsv) infection is associated with an increased risk of both hiv transmission and acquisition. we evaluated longitudinal hsv serology and sexually transmitted infections (stis) among active duty us air force (usaf) members with hiv infection.201626615389
predictors of outcome in hsv encephalitis.this study aims to explore the clinical features, radiological findings, management and the factors influencing prognosis in pcr-confirmed herpes simplex virus encephalitis (hse). this is a retrospective review of consecutive patients diagnosed with hse at mayo clinic, rochester, mn, between january 1995 and december 2013. only hse cases confirmed by pcr were included. univariate and multivariate analysis was used to identify factors associated with good (modified rankin scale of 0-2) or poor ou ...201626568560
herpes simplex induced necrotizing tonsillitis in an immunocompromised patient with ulcerative colitis.we here present the case of a 22-year-old female of suriname ethnicity with ulcerative colitis who received treatment with mercaptopurine and infliximab. she presented herself with a severe necrotizing tonsillitis due to herpes simplex virus type-1 (hsv-1). combination therapy consisting of immunomodulators and anti-tumor necrosis factor (tnf) agents is increasingly being used. anti-tnf therapy is associated with an increased risk of developing serious infections, and especially patients receivi ...201626881193
protection from lethal herpes simplex virus type 1 infection by vaccination with a ul41-deficient recombinant strain.the ul41 gene of herpes simplex virus type 1 (hsv-1) encodes a virion host shut off protein which is involved in immune evasion.　the growth and virulence of hsv-1 is markedly reduced by the deletion of ul41.　in this report, the ul41-deleted recombinant hsv-1 strain vr∆41 was evaluated as a prophylactic live attenuated vaccine against lethal hsv-1 infection in a mouse model.　intraperitoneal (i.p.) inoculation with the vr∆41 strain clearly inhibited lethal wild-type hsv-1 (vr-3 strain) infection a ...201626983589
alphaherpesvirus latency: a dynamic state of transcription and reactivation.alphaherpesviruses infect a variety of species from sea turtles to man and can cause significant disease in mammals including humans and livestock. these viruses are characterized by a lytic and latent state in nerve ganglia, with the ability to establish a lifelong latent infection that is interrupted by periodic reactivation. previously, it was accepted that latency was a dominant state and that only during relatively infrequent reactivation episodes did latent genomes within ganglia become tr ...201626997590
antiviral activity of hatay propolis against replication of herpes simplex virus type 1 and type 2.background propolis is a bee product widely used in folk medicine and possessing many pharmacological properties. in this study we aimed to investigate: i) the antiviral activities of hatay propolis samples against hsv-1 and hsv-2 in hep-2 cell line, and ii) the presence of the synergistic effects of propolis with acyclovir against these viruses. material and methods all experiments were carried out in hep-2 cell cultures. proliferation assays were performed in 24-well flat bottom microplates. w ...201626856414
the agma1 poly(amidoamine) inhibits the infectivity of herpes simplex virus in cell lines, in human cervicovaginal histocultures, and in vaginally infected mice.the development of topical microbicides is a valid approach to protect the genital mucosa from sexually transmitted infections that cannot be contained with effective vaccination, like hsv and hiv infections. a suitable target of microbicides is the interaction between viral proteins and cell surface heparan sulfate proteoglycans (hspgs). agma1 is a prevailingly cationic agmatine-containing polyamidoamine polymer previously shown to inhibit hspgs dependent viruses, including hsv-1, hsv-2, and hp ...201626854390
characterization of the nuclear import mechanisms of hsv-1 ul31.as an important protein, ul31 has been demonstrated to play multiple roles in herpes simplex virus 1 (hsv-1) replication. previous studies showed that ul31 predominantly locates in the nucleus in chemical fixed cells and live cells, however, the determining mechanisms for its nuclear translocation is not clear. in the present study, by utilizing live cells fluorescent microscopy and co-immunoprecipitation assays, the nuclear import of ul31 was characterized to be dependent on ran-, importin α1- ...201626854290
formulation and evaluation of a mucoadhesive thermoresponsive system containing brazilian green propolis for the treatment of lesions caused by herpes simplex type i.the aim of the present work was to develop a topical delivery system that contains brazilian green propolis extract (pe-8) to increase efficiency and convenience when applied to herpetic lesions. the cytotoxicity and antiherpetic activity was determined in vitro and in vivo. the pe-8 was added to a system that contained poloxamer 407 and carbopol 934p. the in vitro characterization of the system included rheological studies, texture profile analysis, and mucoadhesion analysis. the pe-8 inhibited ...201626852846
hsv-1 infection modulates the radioresponse of a hpv16-positive head and neck cancer cell line.the combined effects of human papillomavirus (hpv) and herpes simplex type 1 (hsv-1) infections and their effects on cancer cell radioresistance are unexplored.201626851010
overexpression of thyroid hormone receptor β1 altered thyroid hormone-mediated regulation of herpes simplex virus-1 replication in differentiated cells.thyroid hormone (t3) has been suggested to play a role in herpes simplex virus 1 (hsv-1) replication. it was previously reported that hsv-1 replication was suppressed by t3 in mouse neuroblastoma cells overexpressing thyroid hormone receptor β1 (trβ1). using a human neuro-endocrine cells lncap differentiated by androgen deprivation, hsv-1 replication was active but decreased by t3 at very low moi, probably due to low copy of trβ1. in this study, a recombinant hsv-1 was constructed expressing trβ ...201626843385
frequency of varicella zoster virus dna in human adrenal glands.varicella zoster virus (vzv) becomes latent in ganglionic neurons derived from neural crest cells. because the adrenal gland also contains medullary chromaffin cells of neural crest origin, we examined human adrenal glands and medullary chromaffin cell tumors (pheochromocytomas) for vzv and herpes simplex virus type 1 (hsv-1). we found vzv, but not hsv-1, dna in 4/63 (6 %) normal adrenal glands. no vzv transcripts or antigens were detected in the 4 vzv dna-positive samples. no vzv or hsv-1 dna w ...201626843382
the hsv-1 latency-associated transcript functions to repress latent phase lytic gene expression and suppress virus reactivation from latently infected neurons.herpes simplex virus 1 (hsv-1) establishes life-long latent infection within sensory neurons, during which viral lytic gene expression is silenced. the only highly expressed viral gene product during latent infection is the latency-associated transcript (lat), a non-protein coding rna that has been strongly implicated in the epigenetic regulation of hsv-1 gene expression. we have investigated lat-mediated control of latent gene expression using chromatin immunoprecipitation analyses and lat-nega ...201627055281
novel structure and unexpected rna-binding ability of the c-terminal domain of herpes simplex virus 1 tegument protein ul21.proteins forming the tegument layers of herpesviral virions mediate many essential processes in the viral replication cycle, yet few have been characterized in detail. ul21 is one such multifunctional tegument protein and is conserved among alphaherpesviruses. while ul21 has been implicated in many processes in viral replication, ranging from nuclear egress to virion morphogenesis to cell-cell spread, its precise roles remain unclear. here we report the 2.7-å crystal structure of the c-terminal ...201627053559
high-risk corneal graft rejection in the setting of previous corneal herpes simplex virus (hsv)-1 infection.the "high-risk phenotype" of corneal graft recipients is considered to be related to preexisting vascularization such as that associated with herpes simplex virus-1 (hsv-1) keratitis (hsk). the purpose of this study was to investigate the immunologic mechanisms underlying accelerated corneal graft rejection using a mouse model of hsk.201627050878
extracellular vesicles during herpes simplex virus type 1 infection: an inquire.extracellular vesicles are defined as a heterogeneous group of vesicles that are released by prokaryotic to higher eukaryotic cells and by plant cells in an evolutionary conserved manner. the significance of these vesicles lies in their capacity to transfer selected cargo composed of proteins, lipids and nucleic acids to both recipient and parent cells and to influence various physiological and pathological functions. microorganisms such as parasites, fungi and protozoa and even single cell orga ...201627048572
role of nd10 nuclear bodies in the chromatin repression of hsv-1.herpes simplex virus (hsv) is a neurotropic virus that establishes lifelong latent infection in human ganglion sensory neurons. this unique life cycle necessitates an intimate relation between the host defenses and virus counteractions over the long course of infection. two important aspects of host anti-viral defense, nuclear substructure restriction and epigenetic chromatin regulation, have been intensively studied in the recent years. upon viral dna entering the nucleus, components of discret ...201627048561
herpes simplex virus-1 encephalitis induced by chemoradiotherapy and steroids in an esophageal cancer patient: a case report.systemic chemotherapy combined with steroids used as prophylactic antiemetics have been reported to induce immunosuppression. further, herpes simplex virus-1 (hsv-1) infection has been reported to occur in patients with small cell carcinomas after chemoradiotherapy that includes brain irradiation. here, we report a case of hsv-1 encephalitis that occurred in a patient undergoing chemoradiotherapy for advanced esophageal cancer.201626988237
characterization of the c-terminal nuclease domain of herpes simplex virus pul15 as a target of nucleotidyltransferase inhibitors.the natural product α-hydroxytropolones manicol and β-thujaplicinol inhibit replication of herpes simplex viruses 1 and 2 (hsv-1 and hsv-2, respectively) at nontoxic concentrations. because these were originally developed as divalent metal-sequestering inhibitors of the ribonuclease h activity of hiv-1 reverse transcriptase, α-hydroxytropolones likely target related hsv proteins of the nucleotidyltransferase (ntase) superfamily, which share an "rnase h-like" fold. one potential candidate is pul1 ...201626829613
broad and potent antiviral activity of the nae inhibitor mln4924.in terms of infected human individuals, herpesviruses range among the most successful virus families. subclinical herpesviral infections in healthy individuals contrast with life-threatening syndromes under immunocompromising and immunoimmature conditions. based on our finding that cytomegaloviruses interact with cullin roc ubiquitin ligases (crls) in the context of interferon antagonism, we systematically assessed viral dependency on crls by utilizing the drug mln4924. crl activity is regulated ...201626829401
high conservation of herpes simplex virus ul5/ul52 helicase-primase complex in the era of new antiviral therapies.the emergence of herpes simplex virus (hsv) resistance to current antiviral drugs, that all target the viral dna polymerase, constitutes a major obstacle to antiviral treatment effectiveness of hsv infections, especially in immunocompromised patients. a novel and promising class of inhibitors of the hsv ul5/ul52 helicase-primase (hp) complex has been reported to hinder viral replication with a high potency. in this study, we describe the low natural polymorphism (interstrain identity >99.1% at b ...201626826441
regulable transgene expression in dorsal root ganglia of a replication-defective herpes simplex virus type 1 vector by means of sciatic nerve injection.targeted and controllable gene delivery to neurons is essential to efforts to facilitate peripheral nerve regeneration. the authors investigated both the in vitro and in vivo expression profiles of a tetracycline-controlled, replication-defective, herpes simplex virus type 1-based vector.201626818323
h2ax phosphorylation and dna damage kinase activity are dispensable for herpes simplex virus replication.herpes simplex virus type 1 (hsv-1) can establish both lytic and latent infections in humans. the phosphorylation of histone h2ax, a common marker of dna damage, during lytic infection by hsv-1 is well established. however, the role(s) of h2ax phosphorylation in lytic infection remain unclear.201626817608
probing the nuclear import signal and nuclear transport molecular determinants of prv icp22.herpes simplex virus 1 (hsv-1) icp22 is a multifunctional protein and important for hsv-1 replication. pseudorabies virus (prv) icp22 (p-icp22) is a homologue of hsv-1 icp22 and is reported to be able to selectively modify the transcription of different kinetic classes of prv genes, however, the subcellular localization, localization signal and molecular determinants for its transport to execute this function is less well understood.201626816613
activation of cellular immunity in herpes simplex virus type 1-infected mice by the oral administration of aqueous extract of moringa oleifera lam. leaves.moringa oleifera lam. is used as a nutritive vegetable and spice. its ethanol extract has been previously shown to be significantly effective in alleviating herpetic skin lesions in mice. in this study, we evaluated the alleviation by the aqueous extract (aqmol) and assessed the mode of its anti-herpetic action in a murine cutaneous herpes simplex virus type 1 (hsv-1) infection model. aqmol (300 mg/kg) was administered orally to hsv-1-infected mice three times daily on days 0 to 5 after infectio ...201626814058
extensive cd4 and cd8 t cell cross-reactivity between alphaherpesviruses.the alphaherpesvirinae subfamily includes hsv types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (vzv). t cells, controlled by tcr and hla molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. we show that memory pbmc expansion with either hsv or vzv enriches for cd4 t cell lines that recognize the other agent at the whole-virus, protein, and peptide levels, consistent with bidirectional cross-reactivity. hsv-specific cd4 t ...201626810224
role of proteolipid protein in hsv-1 entry in oligodendrocytic cells.herpes simplex virus type 1 (hsv-1) has the ability to enter many different hosts and cell types by several strategies. this highly prevalent alphaherpesvirus can enter target cells using different receptors and different pathways: fusion at a neutral ph, low-ph-dependent and low-ph-independent endocytosis. several cell receptors for viral entry have been described, but several observations suggest that more receptors for hsv-1 might exist. in this work, we propose a novel role for the proteolip ...201626807581
inhibition of herpes virus infection in oligodendrocyte cultured cells by valproic acid.valproic acid (vpa) is a small fatty acid used for treatment of different neurologic diseases such as epilepsy, migraines or bipolar disorders. vpa modulates different processes of cell metabolism that can lead to alterations in susceptibility of several cell types to the infection of human immunodeficiency virus (hiv), epstein-barr virus (ebv), as well as to exert an inhibitory effect on the replication of different enveloped viruses in cultured cells. taken these data into account and the fact ...201626805038
synthetic α-hydroxytropolones inhibit replication of wild-type and acyclovir-resistant herpes simplex viruses.herpes simplex virus 1 (hsv-1) and hsv-2 remain major human pathogens despite the development of anti-hsv therapeutics as some of the first antiviral drugs. current therapies are incompletely effective and frequently drive the evolution of drug-resistant mutants. we recently determined that certain natural troponoid compounds such as β-thujaplicinol readily suppress hsv-1 and hsv-2 replication. here, we screened 26 synthetic α-hydroxytropolones with the goals of determining a preliminary structu ...201626787704
a central role for sympathetic nerves in herpes stromal keratitis in mice.herpes simplex virus type 1 (hsv-1) is a neurotrophic virus that can cause herpes stromal keratitis (hsk), a severe corneal inflammation that can lead to corneal scarring and blindness. this study identified neurologic changes that occur in hsv-1-infected corneas and related them to hsv-1-induced immunopathology.201627070108
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