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Sample records for dominant-negative recombinant herpes

  1. Immunization with a dominant-negative recombinant Herpes Simplex Virus (HSV type 1 protects against HSV-2 genital disease in guinea pigs

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    Brans Richard

    2010-06-01

    Full Text Available Abstract Background CJ9-gD is a novel dominant-negative recombinant herpes simplex virus type 1 (HSV-1 that is completely replication-defective, cannot establish detectable latent infection in vivo, and expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. In the present study, CJ9-gD was evaluated as a vaccine against HSV-2 genital infection in guinea pigs. Results Animals immunized with CJ9-gD developed at least 700-fold higher titers of HSV-2-specific neutralization antibodies than mock-immunized controls. After challenge with wild-type HSV-2, all 10 control guinea pigs developed multiple genital lesions with an average of 21 lesions per animal. In contrast, only 2 minor lesions were found in 2 of 8 CJ9-gD-immunized animals, representing a 40-fold reduction on the incidence of primary genital lesions in immunized animals (p Conclusions Collectively, we demonstrate that vaccination with the HSV-1 recombinant CJ9-gD elicits strong and protective immune responses against primary and recurrent HSV-2 genital disease and significantly reduces the extent of latent infection.

  2. Response to Multiple Radiation Doses of Human Colorectal Carcinoma Cells Infected With Recombinant Adenovirus Containing Dominant-Negative Ku70 Fragment

    International Nuclear Information System (INIS)

    Urano, Muneyasu; He Fuqiu; Minami, Akiko; Ling, C. Clifton; Li, Gloria C.

    2010-01-01

    Purpose: To investigate the effect of recombinant replication-defective adenovirus containing dominant-negative Ku70 fragment on the response of tumor cells to multiple small radiation doses. Our ultimate goal is to demonstrate the feasibility of using this virus in gene-radiotherapy to enhance the radiation response of tumor cells. Methods and Materials: Human colorectal HCT8 and HT29 carcinoma cells were plated in glass tubes, infected with virus (25 multiplicity of infection), and irradiated with a single dose or zero to five doses of 3 Gy each at 6-h intervals. Hypoxia was induced by flushing with 100% nitrogen gas. The cells were trypsinized 0 or 6 h after the final irradiation, and cell survival was determined by colony formation. The survival data were fitted to linear-quadratic model or exponential line. Results: Virus infection enhanced the radiation response of the HCT8 and HT29 cells. The virus enhancement ratio for single-dose irradiation at a surviving fraction of 0.1 was ∼1.3 for oxic and hypoxic HCT8 and 1.4 and 1.1 for oxic and hypoxic HT29, respectively. A similar virus enhancement ratio of 1.2-1.3 was observed for both oxic and hypoxic cells irradiated with multiple doses; however, these values were smaller than the values found for dominant-negative Ku70-transfected Rat-1 cells. This difference has been discussed. The oxygen enhancement ratio for HCT8 and HT29 receiving fractionated doses was 1.2 and 2.0, respectively, and virus infection altered them slightly. Conclusion: Infection of recombinant replication-defective adenovirus containing dominant-negative Ku70 fragment enhanced the response of human colorectal cancer cells to single and multiple radiation doses.

  3. Two step culture for production of recombinant herpes simplex virus ...

    African Journals Online (AJOL)

    Herpes simplex virus type 2 (HSV-2) was the major cause of genital herpes in humans. The HSV-2 glycoprotein D (gD2) had been proved to be a potentially effective vaccine for treatment of genital herpes. The present study was to develop a two step culture to express the recombinant gD2 protein using the immobilized ...

  4. Vaccinia Virus Recombinant Expressing Herpes Simplex Virus Type 1 Glycoprotein D Prevents Latent Herpes in Mice

    Science.gov (United States)

    Cremer, Kenneth J.; Mackett, Michael; Wohlenberg, Charles; Notkins, Abner Louis; Moss, Bernard

    1985-05-01

    In humans, herpes simplex virus causes a primary infection and then often a latent ganglionic infection that persists for life. Because these latent infections can recur periodically, vaccines are needed that can protect against both primary and latent herpes simplex infections. Infectious vaccinia virus recombinants that contain the herpes simplex virus type 1 (HSV-1) glycoprotein D gene under control of defined early or late vaccinia virus promoters were constructed. Tissue culture cells infected with these recombinant viruses synthesized a glycosylated protein that had the same mass (60,000 daltons) as the glycoprotein D produced by HSV-1. Immunization of mice with one of these recombinant viruses by intradermal, subcutaneous, or intraperitoneal routes resulted in the production of antibodies that neutralized HSV-1 and protected the mice against subsequent lethal challenge with HSV-1 or HSV-2. Immunization with the recombinant virus also protected the majority of the mice against the development of a latent HSV-1 infection of the trigeminal ganglia. This is the first demonstration that a genetically engineered vaccine can prevent the development of latency.

  5. Recombination Promoted by DNA Viruses: Phage λ to Herpes Simplex Virus

    Science.gov (United States)

    Weller, Sandra K.; Sawitzke, James A.

    2015-01-01

    The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. PMID:25002096

  6. Treatment of rat gliomas with recombinant retrovirus harboring Herpes simplex virus thymidine kinase suicide gene

    International Nuclear Information System (INIS)

    Hlavaty, J.; Hlubinova, K.; Altanerova, V.; Liska, J.; Altaner, C.

    1997-01-01

    The retrovirus vector containing Herpes simplex virus type 1 thymidine kinase (HSVtk) gene was constructed. The vector was transfected into the packaging cell line PG13. It was shown that individual transfected cells differ in the production of recombinant retrovirus and in their susceptibility to be killed by ganciclovir. Recombinant retrovirus with a gibbon envelope was able to transduced the HSVtk gene into rat glioma cells. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to influence subcutaneous and intracerebral tumors developed after injection of C 6 rat glioma cells with subsequent injection of HSVtk retrovirus producing cells. (author)

  7. Bioreactor production of recombinant herpes simplex virus vectors.

    Science.gov (United States)

    Knop, David R; Harrell, Heather

    2007-01-01

    Serotypical application of herpes simplex virus (HSV) vectors to gene therapy (type 1) and prophylactic vaccines (types 1 and 2) has garnered substantial clinical interest recently. HSV vectors and amplicons have also been employed as helper virus constructs for manufacture of the dependovirus adeno-associated virus (AAV). Large quantities of infectious HSV stocks are requisite for these therapeutic applications, requiring a scalable vector manufacturing and processing platform comprised of unit operations which accommodate the fragility of HSV. In this study, production of a replication deficient rHSV-1 vector bearing the rep and cap genes of AAV-2 (denoted rHSV-rep2/cap2) was investigated. Adaptation of rHSV production from T225 flasks to a packed bed, fed-batch bioreactor permitted an 1100-fold increment in total vector production without a decrease in specific vector yield (pfu/cell). The fed-batch bioreactor system afforded a rHSV-rep2/cap2 vector recovery of 2.8 x 10(12) pfu. The recovered vector was concentrated by tangential flow filtration (TFF), permitting vector stocks to be formulated at greater than 1.5 x 10(9) pfu/mL.

  8. Expression of Herpes Simplex Virus 1 Glycoprotein B by a Recombinant Vaccinia Virus and Protection of Mice against Lethal Herpes Simplex Virus 1 Infection

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    Cantin, Edouard M.; Eberle, Richard; Baldick, Joseph L.; Moss, Bernard; Willey, Dru E.; Notkins, Abner L.; Openshaw, Harry

    1987-08-01

    The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.

  9. Incorporation of a lambda phage recombination system and EGFP detection to simplify mutagenesis of Herpes simplex virus bacterial artificial chromosomes

    Directory of Open Access Journals (Sweden)

    Weir Jerry P

    2007-05-01

    Full Text Available Abstract Background Targeted mutagenesis of the herpesvirus genomes has been facilitated by the use of bacterial artificial chromosome (BAC technology. Such modified genomes have potential uses in understanding viral pathogenesis, gene identification and characterization, and the development of new viral vectors and vaccines. We have previously described the construction of a herpes simplex virus 2 (HSV-2 BAC and the use of an allele replacement strategy to construct HSV-2 recombinants. While the BAC mutagenesis procedure is a powerful method to generate HSV-2 recombinants, particularly in the absence of selective marker in eukaryotic culture, the mutagenesis procedure is still difficult and cumbersome. Results Here we describe the incorporation of a phage lambda recombination system into an allele replacement vector. This strategy enables any DNA fragment containing the phage attL recombination sites to be efficiently inserted into the attR sites of the allele replacement vector using phage lambda clonase. We also describe how the incorporation of EGFP into the allele replacement vector can facilitate the selection of the desired cross-over recombinant BACs when the allele replacement reaction is a viral gene deletion. Finally, we incorporate the lambda phage recombination sites directly into an HSV-2 BAC vector for direct recombination of gene cassettes using the phage lambda clonase-driven recombination reaction. Conclusion Together, these improvements to the techniques of HSV BAC mutagenesis will facilitate the construction of recombinant herpes simplex viruses and viral vectors.

  10. Incorporation of a lambda phage recombination system and EGFP detection to simplify mutagenesis of Herpes simplex virus bacterial artificial chromosomes.

    Science.gov (United States)

    Schmeisser, Falko; Weir, Jerry P

    2007-05-14

    Targeted mutagenesis of the herpesvirus genomes has been facilitated by the use of bacterial artificial chromosome (BAC) technology. Such modified genomes have potential uses in understanding viral pathogenesis, gene identification and characterization, and the development of new viral vectors and vaccines. We have previously described the construction of a herpes simplex virus 2 (HSV-2) BAC and the use of an allele replacement strategy to construct HSV-2 recombinants. While the BAC mutagenesis procedure is a powerful method to generate HSV-2 recombinants, particularly in the absence of selective marker in eukaryotic culture, the mutagenesis procedure is still difficult and cumbersome. Here we describe the incorporation of a phage lambda recombination system into an allele replacement vector. This strategy enables any DNA fragment containing the phage attL recombination sites to be efficiently inserted into the attR sites of the allele replacement vector using phage lambda clonase. We also describe how the incorporation of EGFP into the allele replacement vector can facilitate the selection of the desired cross-over recombinant BACs when the allele replacement reaction is a viral gene deletion. Finally, we incorporate the lambda phage recombination sites directly into an HSV-2 BAC vector for direct recombination of gene cassettes using the phage lambda clonase-driven recombination reaction. Together, these improvements to the techniques of HSV BAC mutagenesis will facilitate the construction of recombinant herpes simplex viruses and viral vectors.

  11. Evidence for repair of ultraviolet light-damaged herpes virus in human fibroblasts by a recombination mechanism

    International Nuclear Information System (INIS)

    Hall, J.D.; Featherston, J.D.; Almy, R.E.

    1980-01-01

    Human cells were either singly or multiply infected with herpes simplex virus (HSV-1) damaged by ultraviolet (uv) light, and the fraction of cells able to produce infectious virus was measured. The fraction of virus-producing cells was considerably greater for multiply infected cells than for singly infected cells at each uv dose examined. These high survival levels of uv-irradiated virus in multiply infected cells demonstrated that multiplicity-dependent repair, possibly due to genetic exchanges between damaged HSV-1 genomes, was occurring in these cells. To test whether uv light is recombinogenic for HSV-1, the effect of uv irradiation on the yield of temperature-resistant viral recombinants in cells infected with pairs of temperature-sensitive mutants was also investigated. The results of these experiments showed that the defective functions in these mutant host cells are not required for multiplicity-dependent repair or uv-stimulated viral recombination in herpes-infected cells

  12. Incorporation of a lambda phage recombination system and EGFP detection to simplify mutagenesis of Herpes simplex virus bacterial artificial chromosomes

    OpenAIRE

    Weir Jerry P; Schmeisser Falko

    2007-01-01

    Abstract Background Targeted mutagenesis of the herpesvirus genomes has been facilitated by the use of bacterial artificial chromosome (BAC) technology. Such modified genomes have potential uses in understanding viral pathogenesis, gene identification and characterization, and the development of new viral vectors and vaccines. We have previously described the construction of a herpes simplex virus 2 (HSV-2) BAC and the use of an allele replacement strategy to construct HSV-2 recombinants. Whi...

  13. The Neuroinvasive Profiles of H129 (Herpes Simplex Virus Type 1) Recombinants with Putative Anterograde-Only Transneuronal Spread Properties

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    Wojaczynski, Gregory J.; Engel, Esteban A.; Steren, Karina E.; Enquist, Lynn W.; Card, J. Patrick

    2014-01-01

    The use of viruses as transneuronal tracers has become an increasingly powerful technique for defining the synaptic organization of neural networks. Although a number of recombinant alpha herpesviruses are known to spread selectively in the retrograde direction through neural circuits only one strain, the H129 strain of herpes simplex virus type 1, is reported to selectively spread in the anterograde direction. However, it is unclear from the literature whether there is an absolute block or an attenuation of retrograde spread of H129. Here we demonstrate efficient anterograde spread, and temporally delayed retrograde spread, of H129 and three novel recombinants. In vitro studies revealed no differences in anterograde and retrograde spread of parental H129 and its recombinants through superior cervical ganglion neurons. In vivo injections of rat striatum revealed a clear bias of anterograde spread, although evidence of deficient retrograde transport was also present. Evidence of temporally delayed retrograde transneuronal spread of H129 in the retina was observed following injection of the lateral geniculate nucleus. The data also demonstrated that three novel recombinants efficiently express unique fluorescent reporters and have the capacity to infect the same neurons in dual infection paradigms. From these experiments we conclude that H129 and its recombinants efficiently infect neurons through anterograde transneuronal passage, but also are capable of temporally delayed retrograde transneuronal spread. In addition, the capacity to produce dual infection of projection targets following anterograde transneuronal passage provides an important addition to viral transneuronal tracing technology. PMID:24585022

  14. Expression of herpes simplex virus type 1 recombinant thymidine kinase and its application to a rapid antiviral sensitivity assay.

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    Shiota, Tomoyuki; Lixin, Wang; Takayama-Ito, Mutsuyo; Iizuka, Itoe; Ogata, Momoko; Tsuji, Masanori; Nishimura, Hidekazu; Taniguchi, Shuichi; Morikawa, Shigeru; Kurane, Ichiro; Mizuguchi, Masashi; Saijo, Masayuki

    2011-08-01

    Antiviral-resistant herpesvirus infection has become a great concern for immunocompromised patients. Herpes simplex virus type 1 (HSV-1) infections are treated with viral thymidine kinase (vTK)-associated drugs such as acyclovir (ACV), and most ACV-resistance (ACV(r)) is due to mutations in the vTK. The standard drug sensitivity test is usually carried out by the plaque reduction assay-based method, which requires over 10 days. To shorten the time required, a novel system was developed by the concept, in which 293T cells transiently expressing recombinant vTK derived from the test sample by transfection of the cells with an expression vector were infected with vTK-deficient and ACV(r) HSV-1 (TAR), and then cultured in a maintenance medium with or without designated concentrations of ACV, ganciclovir (GCV) and brivudine (BVdU). The replication of TAR was strongly inhibited by ACV, GCV and BVdU in 293T cells expressing recombinant vTK of the ACV-sensitive HSV-1, whereas replication was not or slightly inhibited in cells expressing the recombinant vTK of highly resistant or intermediately resistant HSV-1, respectively. An inverse correlation was demonstrated in the 50% effective concentrations (EC(50)s) and inhibitory effects of these compounds on the replication of TAR among ACV(s) and ACV(r) HSV-1 clones. These results indicate that the EC(50)s of the vTK-associated drugs including ACV can be assumed by measuring the inhibitory effect of drugs in 293T cells expressing recombinant vTK of the target virus. The newly developed antiviral sensitivity assay system for HSV-1 makes it possible to estimate EC(50) for vTK-associated drugs, when whole vTK gene is available for use by gene amplification directly from lesion's samples or from virus isolates. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Dominant negative retinoic acid receptor initiates tumor formation in mice

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    Farias Eduardo F

    2006-03-01

    Full Text Available Abstract Background Retinoic acid suppresses cell growth and promotes cell differentiation, and pharmacological retinoic acid receptor (RAR activation is anti-tumorigenic. This begs the question of whether chronic physiological RAR activation by endogenous retinoids is likewise anti-tumorigenic. Results To address this question, we generated transgenic mice in which expression of a ligand binding defective dominant negative RARα (RARαG303E was under the control of the mouse mammary tumor virus (MMTV promoter. The transgene was expressed in the lymphoid compartment and in the mammary epithelium. Observation of aging mice revealed that transgenic mice, unlike their wild type littermates, developed B cell lymphomas at high penetrance, with a median latency of 40 weeks. MMTV-RARαG303E lymphomas were high grade Pax-5+, surface H+L Ig negative, CD69+ and BCL6- and cytologically and phenotypically resembled human adult high grade (Burkitt's or lymphoblastic lymphomas. We postulated that mammary tumors might arise after a long latency period as seen in other transgenic models of breast cancer. We tested this idea by transplanting transgenic epithelium into the cleared fat pads of wild type hosts, thus bypassing lymphomagenesis. At 17 months post-transplantation, a metastatic mammary adenocarcinoma developed in one of four transplanted glands whereas no tumors developed in sixteen of sixteen endogenous glands with wild type epithelium. Conclusion These findings suggest that physiological RAR activity may normally suppress B lymphocyte and mammary epithelial cell growth and that global RAR inactivation is sufficient to initiate a stochastic process of tumor development requiring multiple transforming events. Our work makes available to the research community a new animal resource that should prove useful as an experimental model of aggressive sporadic lymphoma in immunologically uncompromised hosts. We anticipate that it may also prove useful as a

  16. Properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector

    International Nuclear Information System (INIS)

    Watanabe, Daisuke; Brockman, Mark A.; Ndung'u, Thumbi; Mathews, Lydia; Lucas, William T.; Murphy, Cynthia G.; Felber, Barbara K.; Pavlakis, George N.; Deluca, Neal A.; Knipe, David M.

    2007-01-01

    Herpes simplex virus (HSV) recombinants induce durable immune responses in rhesus macaques and mice and have induced partial protection in rhesus macaques against mucosal challenge with virulent simian immunodeficiency virus (SIV). In this study, we evaluated the properties of a new generation HSV vaccine vector, an HSV-1 multiple immediate-early (IE) gene deletion mutant virus, d106, which contains deletions in the ICP4, ICP27, ICP22, and ICP47 genes. Because several of the HSV IE genes have been implicated in immune evasion, inactivation of the genes encoding these proteins was expected to result in enhanced immunogenicity. The d106 virus expresses few HSV gene products and shows minimal cytopathic effect in cultured cells. When d106 was inoculated into mice, viral DNA accumulated at high levels in draining lymph nodes, consistent with an ability to transduce dendritic cells and activate their maturation and movement to lymph nodes. A d106 recombinant expressing Escherichia coli β-galactosidase induced durable β-gal-specific IgG and CD8 + T cell responses in naive and HSV-immune mice. Finally, d106-based recombinants have been constructed that express simian immunodeficiency virus (SIV) gag, env, or a rev-tat-nef fusion protein for several days in cultured cells. Thus, d106 shows many of the properties desirable in a vaccine vector: limited expression of HSV gene products and cytopathogenicity, high level expression of transgenes, ability to induce durable immune responses, and an ability to transduce dendritic cells and induce their maturation and migration to lymph nodes

  17. High-titer recombinant adeno-associated virus production utilizing a recombinant herpes simplex virus type I vector expressing AAV-2 Rep and Cap.

    Science.gov (United States)

    Conway, J E; Rhys, C M; Zolotukhin, I; Zolotukhin, S; Muzyczka, N; Hayward, G S; Byrne, B J

    1999-06-01

    Recombinant adeno-associated virus type 2 (rAAV) vectors have recently been used to achieve long-term, high level transduction in vivo. Further development of rAAV vectors for clinical use requires significant technological improvements in large-scale vector production. In order to facilitate the production of rAAV vectors, a recombinant herpes simplex virus type I vector (rHSV-1) which does not produce ICP27, has been engineered to express the AAV-2 rep and cap genes. The optimal dose of this vector, d27.1-rc, for AAV production has been determined and results in a yield of 380 expression units (EU) of AAV-GFP produced from 293 cells following transfection with AAV-GFP plasmid DNA. In addition, d27.1-rc was also efficient at producing rAAV from cell lines that have an integrated AAV-GFP provirus. Up to 480 EU/cell of AAV-GFP could be produced from the cell line GFP-92, a proviral, 293 derived cell line. Effective amplification of rAAV vectors introduced into 293 cells by infection was also demonstrated. Passage of rAAV with d27. 1-rc results in up to 200-fold amplification of AAV-GFP with each passage after coinfection of the vectors. Efficient, large-scale production (>109 cells) of AAV-GFP from a proviral cell line was also achieved and these stocks were free of replication-competent AAV. The described rHSV-1 vector provides a novel, simple and flexible way to introduce the AAV-2 rep and cap genes and helper virus functions required to produce high-titer rAAV preparations from any rAAV proviral construct. The efficiency and potential for scalable delivery of d27.1-rc to producer cell cultures should facilitate the production of sufficient quantities of rAAV vectors for clinical application.

  18. Protection from lethal herpes simplex virus type 1 infection by vaccination with a UL41-deficient recombinant strain.

    Science.gov (United States)

    Koshizuka, Tetsuo; Ishioka, Ken; Kobayashi, Takahiro; Ikuta, Kazufumi; Suzutani, Tatsuo

    2016-06-08

    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 after both i.p. and intracerebral (i.c.) inoculations. Vaccination with the VR∆41 strain was safer than VR-3 vaccination and was able to protect against a wild-type challenge to the same degree as VR-3 vaccination. In contrast, i.p. inoculation with ultraviolet-irradiated VR-3 induced resistance against i.p. infection, but not against i.c. Although replication of the VR∆41 strain in mice was greatly reduced compared to that of the VR-3 strain, VR∆41 strain maintained the ability to spread to the central nervous system (CNS) from a peripheral inoculation site. These results indicated that the VR∆41 strain evoked a potent immune reaction through viral protein expression within CNS without the induction of lethal encephalitis. The entry of antigens into the CNS was essential for the establishment of protective immunity against the lethal HSV encephalitis. We concluded that only a live attenuated vaccine is able to afford a prophylactic effect against CNS infection with HSV. In order to fulfill this requirement, UL41-deleted viruses provide a strong candidate for use as a recombinant live vaccine.

  19. Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin made using a recombinant herpes simplex virus production method.

    Science.gov (United States)

    Chulay, Jeffrey D; Ye, Guo-Jie; Thomas, Darby L; Knop, David R; Benson, Janet M; Hutt, Julie A; Wang, Gensheng; Humphries, Margaret; Flotte, Terence R

    2011-02-01

    Recombinant adeno-associated virus (rAAV) vectors offer promise for gene therapy of alpha-1 antitrypsin (AAT) deficiency. A toxicology study in mice evaluated intramuscular injection of an rAAV vector expressing human AAT (rAAV-CB-hAAT) produced using a herpes simplex virus (HSV) complementation system or a plasmid transfection (TFX) method at doses of 3 × 10(11) vg (1.2 × 10(13) vg/kg) for both vectors and 2 × 10(12) vg (8 × 10(13) vg/kg) for the HSV-produced vector. The HSV-produced vector had favorable in vitro characteristics in terms of purity, efficiency of transduction, and hAAT expression. There were no significant differences in clinical findings or hematology and clinical chemistry values between test article and control groups and no gross pathology findings. Histopathological examination demonstrated minimal to mild changes in skeletal muscle at the injection site, consisting of focal chronic interstitial inflammation and muscle degeneration, regeneration, and vacuolization, in vector-injected animals. At the 3 × 10(11) vg dose, serum hAAT levels were higher with the HSV-produced vector than with the TFX-produced vector. With the higher dose of HSV-produced vector, the increase in serum hAAT levels was dose-proportional in females and greater than dose-proportional in males. Vector copy numbers in blood were highest 24 hr after dosing and declined thereafter, with no detectable copies present 90 days after dosing. Antibodies to hAAT were detected in almost all vector-treated animals, and antibodies to HSV were detected in most animals that received the highest vector dose. These results support continued development of rAAV-CB-hAAT for treatment of AAT deficiency.

  20. Herpes - resources

    Science.gov (United States)

    Genital herpes - resources; Resources - genital herpes ... following organizations are good resources for information on genital herpes : March of Dimes -- www.marchofdimes.com/pregnancy/complications- ...

  1. Herpes Keratitis

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    ... Stories Español Eye Health / Eye Health A-Z Herpes Keratitis Sections What is Herpes Keratitis? Herpes Keratitis ... Herpes Keratitis Symptoms Herpes Keratitis Treatment What is Herpes Keratitis? Leer en Español: ¿Qué es la queratitis ...

  2. Genital Herpes

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    Genital herpes is a sexually transmitted disease (STD) caused by a herpes simplex virus (HSV). It can cause sores on ... also infect their babies during childbirth. Symptoms of herpes are called outbreaks. You usually get sores near ...

  3. Flip-Flop HSV-BAC: bacterial artificial chromosome based system for rapid generation of recombinant herpes simplex virus vectors using two independent site-specific recombinases

    Directory of Open Access Journals (Sweden)

    Todo Tomoki

    2006-09-01

    Full Text Available Abstract Background Oncolytic herpes simplex virus (HSV vectors that specifically replicate in and kill tumor cells sparing normal cells are a promising cancer therapy. Traditionally, recombinant HSV vectors have been generated through homologous recombination between the HSV genome and a recombination plasmid, which usually requires laborious screening or selection and can take several months. Recent advances in bacterial artificial chromosome (BAC technology have enabled cloning of the whole HSV genome as a BAC plasmid and subsequent manipulation in E. coli. Thus, we sought a method to generate recombinant oncolytic HSV vectors more easily and quickly using BAC technology. Results We have developed an HSV-BAC system, termed the Flip-Flop HSV-BAC system, for the rapid generation of oncolytic HSV vectors. This system has the following features: (i two site-specific recombinases, Cre and FLPe, are used sequentially to integrate desired sequences and to excise the BAC sequences, respectively; and (ii the size of the HSV-BAC-insert genome exceeds the packaging limit of HSV so only correctly recombined virus grows efficiently. We applied this to the construction of an HSV-BAC plasmid that can be used for the generation of transcriptionally-targeted HSV vectors. BAC sequences were recombined into the UL39 gene of HSV ICP4-deletion mutant d120 to generate M24-BAC virus, from which HSV-BAC plasmid pM24-BAC was isolated. An ICP4 expression cassette driven by an exogenous promoter was re-introduced to pM24-BAC by Cre-mediated recombination and nearly pure preparations of recombinant virus were obtained typically in two weeks. Insertion of the ICP4 coding sequence alone did not restore viral replication and was only minimally better than an ICP4-null construct, whereas insertion of a CMVIE promoter-ICP4 transgene (bM24-CMV efficiently drove viral replication. The levels of bM24-CMV replication in tumor cells varied considerably compared to hrR3 (UL39

  4. Conditional Expression of Human PPARδ and a Dominant Negative Variant of hPPARδ In Vivo

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    Larry G. Higgins

    2012-01-01

    Full Text Available The nuclear receptor, NR1C2 or peroxisome proliferator-activated receptor (PPAR-δ, is ubiquitously expressed and important for placental development, fatty acid metabolism, wound healing, inflammation, and tumour development. PPARδ has been hypothesized to function as both a ligand activated transcription factor and a repressor of transcription in the absence of agonist. In this paper, treatment of mice conditionally expressing human PPARδ with GW501516 resulted in a marked loss in body weight that was not evident in nontransgenic animals or animals expressing a dominant negative derivative of PPARδ. Expression of either functional or dominant negative hPPARδ blocked bezafibrate-induced PPARα-dependent hepatomegaly and blocked the effect of bezafibrate on the transcription of PPARα target genes. These data demonstrate, for the first time, that PPARδ could inhibit the activation of PPARα in vivo and provide novel models for the investigation of the role of PPARδ in pathophysiology.

  5. Pregnancy and herpes

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    HSV; Congenital herpes; Herpes - congenital; Birth-acquired herpes; Herpes during pregnancy ... Newborn infants can become infected with herpes virus: In the uterus (this is ... herpes, the most common method of infection) Right ...

  6. Herpes - oral

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    ... virus type 2 (HSV-2) most often causes genital herpes . However, sometimes HSV-2 is spread to the ... the virus to the genitals. Both oral and genital herpes viruses can sometimes be spread, even when you ...

  7. Genital Herpes

    Science.gov (United States)

    ... legs, buttocks, or genital area Swollen glands Unusual vaginal discharge If you have any symptoms of genital herpes, ... J.M. (2008). Understanding Herpes Simplex Virus: Transmission, Diagnosis, and Considerations in Pregnancy ... ...

  8. Cardioselective Dominant-negative Thyroid Hormone Receptor (Δ337T) Modulates Myocardial Metabolism and Contractile Dfficiency

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    Hyyti, Outi M.; Olson, Aaron; Ge, Ming; Ning, Xue-Han; Buroker, Norman E.; Chung, Youngran; Jue, Thomas; Portman, Michael A.

    2008-06-03

    Dominant- negative thyroid hormone receptors (TRs) show elevated expression relative to ligand-binding TRs during cardiac hypertrophy. We tested the hypothesis that overexpression of a dominant-negative TR alters cardiac metabolism and contractile efficiency (CE). We used mice expressing the cardioselective dominant-negative TRβ1 mutation Δ337T. Isolated working Δ337T hearts and nontransgenic control (Con) hearts were perfused with 13C-labeled free fatty acids (FFA), acetoacetate (ACAC), lactate, and glucose at physiological concentrations for 30 min. 13C NMR spectroscopy and isotopomer analyses were used to determine substrate flux and fractional contributions (Fc) of acetyl-CoA to the citric acid cycle (CAC). Δ337T hearts exhibited rate depression but higher developed pressure and CE, defined as work per oxygen consumption (MV˙ O2). Unlabeled substrate Fc from endogenous sources was higher in Δ337T, but ACAC Fc was lower. Fluxes through CAC, lactate, ACAC, and FFA were reduced in Δ337T. CE and Fc differences were reversed by pacing Δ337T to Con rates, accompanied by an increase in FFA Fc. Δ337T hearts lacked the ability to increase MV˙ O2. Decreases in protein expression for glucose transporter-4 and hexokinase-2 and increases in pyruvate dehydrogenase kinase-2 and -4 suggest that these hearts are unable to increase carbohydrate oxidation in response to stress. These data show that Δ337T alters the metabolic phenotype in murine heart by reducing substrate flux for multiple pathways. Some of these changes are heart rate dependent, indicating that the substrate shift may represent an accommodation to altered contractile protein kinetics, which can be disrupted by pacing stress.

  9. Glassy-state stabilization of a dominant negative inhibitor anthrax vaccine containing aluminum hydroxide and glycopyranoside lipid A adjuvants.

    Science.gov (United States)

    Hassett, Kimberly J; Vance, David J; Jain, Nishant K; Sahni, Neha; Rabia, Lilia A; Cousins, Megan C; Joshi, Sangeeta; Volkin, David B; Middaugh, C Russell; Mantis, Nicholas J; Carpenter, John F; Randolph, Theodore W

    2015-02-01

    During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better understand and prevent such losses, dominant negative inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. Immunogenicity of liquid vaccines also decreased when stored at 40°C for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40°C. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40°C and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40°C were observed. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Non-DNA binding, dominant-negative, human PPARγ mutations cause lipodystrophic insulin resistance

    Science.gov (United States)

    Agostini, Maura; Schoenmakers, Erik; Mitchell, Catherine; Szatmari, Istvan; Savage, David; Smith, Aaron; Rajanayagam, Odelia; Semple, Robert; Luan, Jian'an; Bath, Louise; Zalin, Anthony; Labib, Mourad; Kumar, Sudhesh; Simpson, Helen; Blom, Dirk; Marais, David; Schwabe, John; Barroso, Inês; Trembath, Richard; Wareham, Nicholas; Nagy, Laszlo; Gurnell, Mark; O'Rahilly, Stephen; Chatterjee, Krishna

    2006-01-01

    Summary PPARγ is essential for adipogenesis and metabolic homeostasis. We describe mutations in the DNA and ligand binding domains of human PPARγ in lipodystrophic, severe insulin resistance. These receptor mutants lack DNA binding and transcriptional activity but can translocate to the nucleus, interact with PPARγ coactivators and inhibit coexpressed wild-type receptor. Expression of PPARγ target genes is markedly attenuated in mutation-containing versus receptor haploinsufficent primary cells, indicating that such dominant-negative inhibition operates in vivo. Our observations suggest that these mutants restrict wild-type PPARγ action via a non-DNA binding, transcriptional interference mechanism, which may involve sequestration of functionally limiting coactivators. PMID:17011503

  11. Cancer-associated PTEN mutants act in a dominant negative manner to suppress PTEN protein function

    OpenAIRE

    Papa, Antonella; Wan, Lixin; Bonora, Massimo; Salmena, Leonardo; Song, Min Sup; Hobbs, Robin M.; Lunardi, Andrea; Webster, Kaitlyn; Ng, Christopher; Newton, Ryan H.; Knoblauch, Nicholas; Guarnerio, Jlenia; Ito, Keisuke; Turka, Laurence A.; Beck, Andy H.

    2014-01-01

    PTEN dysfunction plays a crucial role in the pathogenesis of hereditary and sporadic cancers. Here we show that PTEN homo-dimerizes, and in this active conformation exerts lipid phosphatase activity on PtdIns(3,4,5)P3. We demonstrate that catalytically inactive cancer-associated PTEN mutants hetero-dimerize with wild-type PTEN and constrain its phosphatase activity in a dominant-negative manner. To study the consequences of homo- and hetero-dimerization of wild-type and mutant PTEN in vivo, w...

  12. A dominant negative zebrafish Ahr2 partially protects developing zebrafish from dioxin toxicity.

    Directory of Open Access Journals (Sweden)

    Kevin A Lanham

    Full Text Available The toxicity by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD is thought to be caused by activation of the aryl hydrocarbon receptor (AHR. However, our understanding of how AHR activation by TCDD leads to toxic effects is poor. Ideally we would like to manipulate AHR activity in specific tissues and at specific times. One route to this is expressing dominant negative AHRs (dnAHRs. This work describes the construction and characterization of dominant negative forms of the zebrafish Ahr2 in which the C-terminal transactivation domain was either removed, or replaced with the inhibitory domain from the Drosophila engrailed repressor protein. One of these dnAhr2s was selected for expression from the ubiquitously active e2fα promoter in transgenic zebrafish. We found that these transgenic zebrafish expressing dnAhr2 had reduced TCDD induction of the Ahr2 target gene cyp1a, as measured by 7-ethoxyresorufin-O-deethylase activity. Furthermore, the cardiotoxicity produced by TCDD, pericardial edema, heart malformation, and reduced blood flow, were all mitigated in the zebrafish expressing the dnAhr2. These results provide in vivo proof-of-principle results demonstrating the effectiveness of dnAHRs in manipulating AHR activity in vivo, and demonstrating that this approach can be a means for blocking TCDD toxicity.

  13. The Bipolar Filaments Formed by Herpes Simplex Virus Type 1 SSB/Recombination Protein (ICP8) Suggest a Mechanism for DNA Annealing

    Energy Technology Data Exchange (ETDEWEB)

    Makhov, A.M.; Simon, M.; Sen, A.; Yu, X.; Griffith, J. D.; Egelman, E. H.

    2009-02-20

    Herpes simplex virus type 1 encodes a multifunctional protein, ICP8, which serves both as a single-strand binding protein and as a recombinase, catalyzing reactions involved in replication and recombination of the viral genome. In the presence of divalent ions and at low temperature, previous electron microscopic studies showed that ICP8 will form long left-handed helical filaments. Here, electron microscopic image reconstruction reveals that the filaments are bipolar, with an asymmetric unit containing two subunits of ICP8 that constitute a symmetrical dimer. This organization of the filament has been confirmed using scanning transmission electron microscopy. The pitch of the filaments is {approx} 250 {angstrom}, with {approx} 6.2 dimers per turn. Docking of a crystal structure of ICP8 into the reconstructed filament shows that the C-terminal domain of ICP8, attached to the body of the subunit by a flexible linker containing {approx} 10 residues, is packed into a pocket in the body of a neighboring subunit in the crystal in a similar manner as in the filament. However, the interactions between the large N-terminal domains are quite different in the filament from that observed in the crystal. A previously proposed model for ICP8 binding single-stranded DNA (ssDNA), based upon the crystal structure, leads to a model for a continuous strand of ssDNA near the filament axis. The bipolar nature of the ICP8 filaments means that a second strand of ssDNA would be running through this filament in the opposite orientation, and this provides a potential mechanism for how ICP8 anneals complementary ssDNA into double-stranded DNA, where each strand runs in opposite directions.

  14. Suppressing autoimmunity in Arabidopsis thaliana with dominant negative immune receptors

    DEFF Research Database (Denmark)

    Greeff, Michael Christiaan

    Cell Death 11 (acd11) leads to inappropriate activation of hypersensitive cell death. We have previously performed a large-scale survival screen for suppressors of acd11 and found that cell death in acd11 is suppressed by mutations in a gene encoding an R protein. We have thus proposed that loss of ACD......11 results in HR cell death because LAZ5 directly or indirectly guards it. The LAZ5 alleles we first found were dominant negative (laz5-DN). The laz-DN allele mutation was found in a conserved functionally important ATP binding region, the P-loop. Site-directed DN mutant alleles can be made for other......A small set of Resistance proteins (R-proteins), guards plants against a large set of pathogen effector proteins that can suppress or subvert plant defense responses. The guard model attempts to solve this discrepancy by proposing that a major function of R proteins is to monitor host effector...

  15. Functional analysis of a dominant negative mutation of interferon regulatory factor 5.

    Directory of Open Access Journals (Sweden)

    Long Yang

    Full Text Available BACKGROUND: Interferon regulatory factor (IRF family members have been implicated as critical transcription factors that function in immune response, hematopoietic differentiation and cell growth regulation. Activation of IRF-5 results in the production of pro-inflammatory cytokines such as TNFalpha, IL6 and IL12p40, as well as type I interferons. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we identify a G202C (position relative to translation start codon missense-mutation transcript of IRF-5 in transformed B and T cell lines, which were either infected or non-infected by viruses, and peripheral blood from ATL or CLL patients. The mutated transcript encodes a novel protein in which the sixty-eighth amino acid, Alanine, is substituted by Proline (IRF-5P68 in the DNA binding domain of IRF-5. IRF-5P68 phenotype results in a complete loss of its DNA-binding activity and functions as a dominant negative molecule through interacting with wild type IRF-5. Co-expression of IRF-5P68 inhibits MyD88-mediated IRF-5 transactivation. Moreover, Toll-like receptor (TLR-dependent IL6 and IL12P40 production induced by lipopolysaccharide (LPS, R837 or CpG ODN 1826 was reduced in IRF-5 (P68 expressing cells as compared to the control cells. CONCLUSION: IRF-5P68 acts as a dominant negative regulator that interferes with IRF-5-mediated production of pro-inflammatory cytokines. The functional characterization of the novel IRF-5 mutant in transformed B and T cell lines and in ATL and CLL patients may lead to a better understanding of the role of these transcriptional regulators in hematopoietic malignancies.

  16. Recombinant adeno-associated virus type 2 replication and packaging is entirely supported by a herpes simplex virus type 1 amplicon expressing Rep and Cap.

    Science.gov (United States)

    Conway, J E; Zolotukhin, S; Muzyczka, N; Hayward, G S; Byrne, B J

    1997-11-01

    Recombinant adeno-associated virus (AAV) type 2 (rAAV) vectors have recently been shown to have great utility as gene transfer agents both in vitro and in vivo. One of the problems associated with the use of rAAV vectors has been the difficulty of large-scale vector production. Low-efficiency plasmid transfection of the rAAV vector and complementing AAV type 2 (AAV-2) functions (rep and cap) followed by superinfection with adenovirus has been the standard approach to rAAV production. The objectives of this study were to demonstrate the ability of a recombinant herpes simplex virus type 1 (HSV-1) amplicon expressing AAV-2 Rep and Cap to support replication and packaging of rAAV vectors. HSV-1 amplicon vectors were constructed which contain the AAV-2 rep and cap genes under control of their native promoters (p5, p19, and p40). An HSV-1 amplicon vector, HSV-RC/KOS or HSV-RC/d27, was generated by supplying helper functions with either wild-type HSV-1 (KOS strain) or the ICP27-deleted mutant of HSV-1, d27-1, respectively. Replication of the amplicon stocks is not inhibited by the presence of AAV-2 Rep proteins, which highlights important differences between HSV-1 and adenovirus replication and the mechanism of providing helper function for productive AAV infection. Coinfection of rAAV and HSV-RC/KOS resulted in the replication and amplification of rAAV genomes. Similarly, rescue and replication of rAAV genomes occurred when rAAV vector plasmids were transfected into cells followed by HSV-RC/KOS infection and when two rAAV proviral cell lines were infected with HSV-RC/KOS or HSV-RC/d27. Production of infectious rAAV by rescue from two rAAV proviral cell lines has also been achieved with HSV-RC/KOS and HSV-RC/d27. The particle titer of rAAV produced with HSV-RC/d27 is equal to that achieved by supplying rep and cap by transfection followed by adenovirus superinfection. Importantly, no detectable wild-type AAV-2 is generated with this approach. These results demonstrate

  17. Genital herpes

    OpenAIRE

    Hollier, Lisa M; Straub, Heather

    2011-01-01

    Genital herpes is an infection with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2). The typical clinical features include painful shallow anogenital ulceration. It is among the most common sexually transmitted diseases, with up to 23% of adults in the UK and US having antibodies to HSV-2.

  18. A dominant-negative mutant inhibits multiple prion variants through a common mechanism.

    Directory of Open Access Journals (Sweden)

    Fen Pei

    2017-10-01

    Full Text Available Prions adopt alternative, self-replicating protein conformations and thereby determine novel phenotypes that are often irreversible. Nevertheless, dominant-negative prion mutants can revert phenotypes associated with some conformations. These observations suggest that, while intervention is possible, distinct inhibitors must be developed to overcome the conformational plasticity of prions. To understand the basis of this specificity, we determined the impact of the G58D mutant of the Sup35 prion on three of its conformational variants, which form amyloids in S. cerevisiae. G58D had been previously proposed to have unique effects on these variants, but our studies suggest a common mechanism. All variants, including those reported to be resistant, are inhibited by G58D but at distinct doses. G58D lowers the kinetic stability of the associated amyloid, enhancing its fragmentation by molecular chaperones, promoting Sup35 resolubilization, and leading to amyloid clearance particularly in daughter cells. Reducing the availability or activity of the chaperone Hsp104, even transiently, reverses curing. Thus, the specificity of inhibition is determined by the sensitivity of variants to the mutant dosage rather than mode of action, challenging the view that a unique inhibitor must be developed to combat each variant.

  19. Study of Vaccinia and Cowpox viruses' replication in Rac1-N17 dominant-negative cells

    Directory of Open Access Journals (Sweden)

    Ana Paula Carneiro Salgado

    2013-08-01

    Full Text Available Interfering with cellular signal transduction pathways is a common strategy used by many viruses to create a propitious intracellular environment for an efficient replication. Our group has been studying cellular signalling pathways activated by the orthopoxviruses Vaccinia (VACV and Cowpox (CPXV and their significance to viral replication. In the present study our aim was to investigate whether the GTPase Rac1 was an upstream signal that led to the activation of MEK/ERK1/2, JNK1/2 or Akt pathways upon VACV or CPXV' infections. Therefore, we generated stable murine fibroblasts exhibiting negative dominance to Rac1-N17 to evaluate viral growth and the phosphorylation status of ERK1/2, JNK1/2 and Akt. Our results demonstrated that VACV replication, but not CPXV, was affected in dominant-negative (DN Rac1-N17 cell lines in which viral yield was reduced in about 10-fold. Viral late gene expression, but not early, was also reduced. Furthermore, our data showed that Akt phosphorylation was diminished upon VACV infection in DN Rac1-N17 cells, suggesting that Rac1 participates in the phosphoinositide-3 kinase pathway leading to the activation of Akt. In conclusion, our results indicate that while Rac1 indeed plays a role in VACV biology, perhaps another GTPase may be involved in CPXV replication.

  20. A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR– B cells

    Science.gov (United States)

    Boisson, Bertrand; Wang, Yong-Dong; Bosompem, Amma; Ma, Cindy S.; Lim, Annick; Kochetkov, Tatiana; Tangye, Stuart G.; Casanova, Jean-Laurent; Conley, Mary Ellen

    2013-01-01

    Approximately 90% of patients with isolated agammaglobulinemia and failure of B cell development have mutations in genes required for signaling through the pre–B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agammaglobulinemia and markedly decreased numbers of peripheral B cells. The B cells that could be detected had an unusual phenotype characterized by the increased expression of CD19 but the absence of a B cell receptor. Genetic studies demonstrated that all 4 patients had the exact same de novo mutation in the broadly expressed transcription factor E47. The mutant protein (E555K) was stable in patient-derived EBV-transformed cell lines and cell lines transfected with expression vectors. E555K in the transfected cells localized normally to the nucleus and resulted in a dominant negative effect when bound to DNA as a homodimer with wild-type E47. Mutant E47 did permit DNA binding by a tissue-specific heterodimeric DNA-binding partner, myogenic differentiation 1 (MYOD). These findings document a mutational hot-spot in E47 and represent an autosomal dominant form of agammaglobulinemia. Further, they indicate that E47 plays a critical role in enforcing the block in development of B cell precursors that lack functional antigen receptors. PMID:24216514

  1. A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells.

    Science.gov (United States)

    Boisson, Bertrand; Wang, Yong-Dong; Bosompem, Amma; Ma, Cindy S; Lim, Annick; Kochetkov, Tatiana; Tangye, Stuart G; Casanova, Jean-Laurent; Conley, Mary Ellen

    2013-11-01

    Approximately 90% of patients with isolated agammaglobulinemia and failure of B cell development have mutations in genes required for signaling through the pre–B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agammaglobulinemia and markedly decreased numbers of peripheral B cells. The B cells that could be detected had an unusual phenotype characterized by the increased expression of CD19 but the absence of a B cell receptor. Genetic studies demonstrated that all 4 patients had the exact same de novo mutation in the broadly expressed transcription factor E47. The mutant protein (E555K) was stable in patient-derived EBV-transformed cell lines and cell lines transfected with expression vectors. E555K in the transfected cells localized normally to the nucleus and resulted in a dominant negative effect when bound to DNA as a homodimer with wild-type E47. Mutant E47 did permit DNA binding by a tissue-specific heterodimeric DNA-binding partner, myogenic differentiation 1 (MYOD). These findings document a mutational hot-spot in E47 and represent an autosomal dominant form of agammaglobulinemia. Further, they indicate that E47 plays a critical role in enforcing the block in development of B cell precursors that lack functional antigen receptors.

  2. Dominant negative mutations of Caenorhabditis elegans daf-7 confer a novel developmental phenotype.

    Science.gov (United States)

    Crook, Matt; Grant, Warwick N

    2013-06-01

    TGF-β signaling pathways are involved in the control of development in every member of the animal kingdom. As such, TGF-β ligands are widely divergent yet retain a set of core conserved features, specifically, a pre-protein cleavage site and several conserved ligand domain residues, the disruption of which produces a dominant negative phenotype. We have extended these observations into an invertebrate system by creating a series of loss-of-function Caenorhabditis elegans daf-7 transgenes. When we tested these mutant transgenes in a daf-7/+ background, we saw a molting and excretory canal phenotype. Members of both pathways downstream of daf-4 were required for this phenotype. Our results show that the basic mechanisms of TGF-β function are conserved across the animal kingdom. A subset of our daf-7 mutations also produced an unexpected and novel phenotype. Epistasis experiments demonstrated that both daf-3/-5 and sma-4/-9 were downstream of our mutant daf-7 transgenes, which suggests not only a role for DAF-7 in the control of molting and the development of the excretory system but also that daf-7 and dbl-1 signaling may converge downstream of their shared Type II receptor, daf-4. Our approach may unveil new roles in development for other invertebrate TGF-β ligands. Copyright © 2013 Wiley Periodicals, Inc.

  3. Dominant negative actions of human prostacyclin receptor variant through dimerization: implications for cardiovascular disease.

    Science.gov (United States)

    Ibrahim, Salam; Tetruashvily, Mazell; Frey, Alex J; Wilson, Stephen J; Stitham, Jeremiah; Hwa, John; Smyth, Emer M

    2010-09-01

    Prostacyclin and thromboxane mediate opposing cardiovascular effects through their receptors, the prostacyclin receptor (IP) and thromboxane receptor (TP). Individuals heterozygous for an IP variant, IP(R212C), displayed exaggerated loss of platelet IP responsiveness and accelerated cardiovascular disease. We examined association of IP(R212C) into homo- and heterodimeric receptor complexes and the impact on prostacyclin and thromboxane biology. Dimerization of the IP, IP(R212C), and TPalpha was examined by bioluminesence resonance energy transfer in transfected HEK293 cells. We observed an equal propensity for formation of IPIP homodimers and IPTPalpha heterodimers. Compared with the IP alone, IP(R212C) displayed reduced cAMP generation and increased endoplasmic reticulum localization but underwent normal homo- and heterodimerization. When the IP(R212C) and IP were coexpressed, a dominant negative action of the variant was evident with enhanced wild-type IP localization to the endoplasmic reticulum and reduced agonist-dependent signaling. Further, the TPalpha activation response, which was shifted from inositol phosphate to cAMP generation following IPTPalpha heterodimerization, was normalized when the TPalpha instead dimerized with IP(R212C). IP(R212C) exerts a dominant action on the wild-type IP and TPalpha through dimerization. This likely contributes to accelerated cardiovascular disease in individuals carrying 1 copy of the variant allele.

  4. A cancer-predisposing "hot spot" mutation of the fumarase gene creates a dominant negative protein.

    Science.gov (United States)

    Lorenzato, Annalisa; Olivero, Martina; Perro, Mario; Brière, Jean Jacques; Rustin, Pierre; Di Renzo, Maria Flavia

    2008-02-15

    The Fumarase (Fumarate Hydratase, FH) is a tumor suppressor gene whose germline heterozygous mutations predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). The FH gene encodes an enzyme of the Krebs cycle, functioning as a homotetramer and catalyzing the hydration of fumarate to malate. Among the numerous FH mutations reported so far, the R190H missense mutation is the most frequent in HLRCC patients. Here we show the functional analyses of the R190H, in comparison to the better characterized E319Q mutation. We first expressed wild-type and mutated proteins in FH deficient human skin fibroblasts, using lentiviral vectors. The wild-type transgene was able to restore the FH enzymatic activity in cells, while the R190H- and E319Q-FH were not. More interestingly, when the same transgenes were expressed in normal, FH-proficient cells, only the R190H-FH reduced the endogenous FH enzymatic activity. By enforcing the expression of equal amount of wild-type and R190H-FH in the same cell, we showed that the mutated FH protein directly inhibited enzymatic activity by nearly abrogating the FH homotetramer formation. These data demonstrate the dominant negative effect of the R190H missense mutation in the FH gene and suggest that the FH tumor-suppressing activity might be impaired in cells carrying a heterozygous mutation. (c) 2007 Wiley-Liss, Inc.

  5. Response to Multiple Radiation Doses of Fibroblasts Over-Expressing Dominant Negative Ku70

    International Nuclear Information System (INIS)

    Urano, Muneyasu; Huang Yunhong; He Fuqiu; Minami, Akiko; Ling, C. Clifton; Li, Gloria C.

    2008-01-01

    Purpose: To evaluate the response of cells over-expressing dominant negative (DN) Ku70 to single and multiple small radiation doses. Methods and Materials: Clones of fibroblasts over-expressing DNKu70, DNKu70-7, DNKu70-11, and parental Rat-1 cells were irradiated under oxic or hypoxic conditions with single or multiple doses. Cells were trypsinized 0 or 6 h after irradiation to determine surviving fraction (SF). Results: Oxic DNKu70-7 or -11 cells trypsinized 6 h after irradiation were 1.52 or 1.25 and 1.28 or 1.15 times more sensitive than oxic Rat-1 at SF of 0.5 and 0.1, respectively. Hypoxic DNKu70-7 or -11 cells trypsinized 6 h after irradiation were 1.44 or 1.70 and 1.33 or 1.51 times more sensitive than hypoxic Rat-1 at SF of 0.5 and 0.1, respectively. To the multiple doses, oxic and hypoxic DNKu70-7 or -11 cells were 1.35 or 1.37 and 2.23 or 4.61 times more sensitive than oxic and hypoxic Rat-1, respectively, resulting in very small oxygen enhancement ratios. Namely, enhancement caused by DNKu70 under hypoxia after multiple doses was greater than that under oxic conditions and greater than that after single dose. Conclusions: Over-expression of DNKu70 enhances cells' response to radiation given as a single dose and as multiple small doses. The enhancement after multiple doses was stronger under hypoxic than under oxic conditions. These results encourage the use of DNKu70 fragment in a gene-radiotherapy

  6. Dominant-negative CK2alpha induces potent effects on circadian rhythmicity.

    Directory of Open Access Journals (Sweden)

    Elaine M Smith

    2008-01-01

    Full Text Available Circadian clocks organize the precise timing of cellular and behavioral events. In Drosophila, circadian clocks consist of negative feedback loops in which the clock component PERIOD (PER represses its own transcription. PER phosphorylation is a critical step in timing the onset and termination of this feedback. The protein kinase CK2 has been linked to circadian timing, but the importance of this contribution is unclear; it is not certain where and when CK2 acts to regulate circadian rhythms. To determine its temporal and spatial functions, a dominant negative mutant of the catalytic alpha subunit, CK2alpha(Tik, was targeted to circadian neurons. Behaviorally, CK2alpha(Tik induces severe period lengthening (approximately 33 h, greater than nearly all known circadian mutant alleles, and abolishes detectable free-running behavioral rhythmicity at high levels of expression. CK2alpha(Tik, when targeted to a subset of pacemaker neurons, generates period splitting, resulting in flies exhibiting both long and near 24-h periods. These behavioral effects are evident even when CK2alpha(Tik expression is induced only during adulthood, implicating an acute role for CK2alpha function in circadian rhythms. CK2alpha(Tik expression results in reduced PER phosphorylation, delayed nuclear entry, and dampened cycling with elevated trough levels of PER. Heightened trough levels of per transcript accompany increased protein levels, suggesting that CK2alpha(Tik disturbs negative feedback of PER on its own transcription. Taken together, these in vivo data implicate a central role of CK2alpha function in timing PER negative feedback in adult circadian neurons.

  7. Generation of a Retinoblastoma (Rb1-inducible dominant negative (DN mouse model

    Directory of Open Access Journals (Sweden)

    Shikha eTarang

    2015-02-01

    Full Text Available Retinoblastoma 1 (Rb1 is an essential gene regulating cellular proliferation, differentiation, and homeostasis. To exert these functions, Rb1 is recruited and physically interacts with a growing variety of signaling pathways. While Rb1 does not appear to be ubiquitously expressed, its expression has been confirmed in a variety of hematopoietic and neuronal-derived cells, including the inner ear hair cells (HCs. Studies in transgenic mice demonstrate that complete germline or conditional Rb1 deletion leads to abnormal cell proliferation, followed by massive apoptosis; making it difficult to fully address Rb1’s biochemical activities. To overcome these limitations, we developed a tetracycline-inducible TetO-CB-myc6-Rb1 (CBRb mouse model to achieve transient and inducible dominant negative (DN inhibition of the endogenous RB1 protein. Our strategy involved fusing the Rb1 gene to the lysosomal protease pre-procathepsin B (CB, thus allowing for further routing of the DN-CBRb fusion protein and its interacting complexes for proteolytic degradation. Moreover, reversibility of the system is achieved upon suppression of doxycycline (Dox administration. Preliminary characterization of DN-CBRb mice bred to a ubiquitous rtTA mouse line demonstrated a significant inhibition of the endogenous RB1 protein in the inner ear and in a number of other organs where RB1 is expressed. Examination of the postnatal (P DN-CBRb mice inner ear at P10 and P28 showed the presence of supernumerary inner HCs in the lower turns of the cochleae, which corresponds to the described expression domain of the endogenous Rb1 gene. Selective and reversible suppression of gene expression is both an experimental tool for defining function and a potential means to medical therapy. Given the limitations associated with Rb1-null mice lethality, this model provides a valuable resource for understanding RB1 activity, relative contribution to HC regeneration and its potential therapeutic

  8. Induced expression of nucleolin phosphorylation-deficient mutant confers dominant-negative effect on cell proliferation.

    Directory of Open Access Journals (Sweden)

    Shu Xiao

    Full Text Available Nucleolin (NCL is a major nucleolar phosphoprotein that has pleiotropic effects on cell proliferation and is elevated in a variety of tumors. NCL is highly phosphorylated at the N-terminus by two major kinases: interphase casein kinase 2 (CK2 and mitotic cyclin-dependent kinase 1 (CDK1. Earlier we demonstrated that a NCL-mutant that is partly defective in undergoing phosphorylation by CK2 inhibits chromosomal replication through its interactions with Replication Protein A, mimicking the cellular response to DNA damage. We further delineated that the N-terminus of NCL associates with Hdm2, the most common E3 ubiquitin ligase of p53. We reported that NCL antagonizes Hdm2 to stabilize p53 and stimulates p53 transcriptional activity. Although NCL-phosphorylation by CK2 and ribosomal DNA transcription are closely coordinated during interphase, the role of NCL phosphorylation in regulating cell proliferation remains unexplored. We have therefore engineered unique human cells that specifically induce expression of NCL-wild type (WT or a phosphorylation-deficient NCL-mutant, 6/S*A where all the six CK2 consensus serine sites residing in the N-terminus NCL were mutated to alanine. Here we show that this NCL-mutant is defective in undergoing phosphorylation by CK2. We also demonstrate that NCL-phosphorylation by CK2 is required through the S-phase progression in cell cycle and hence proliferation. Induced expression of NCL with mutated CK2 phosphorylation sites stabilizes p53, results in higher expression of Bcl2 (B-cell lymphoma 2 homology 3 (BH3-only apoptotic markers and causes a dominant-negative effect on cell viability. Our unique cellular system thus provides the first evidential support to delineate phospho-specific functions of NCL on cell proliferation.

  9. Serum herpes simplex antibodies

    Science.gov (United States)

    ... causes cold sores (oral herpes). HSV-2 causes genital herpes. How the Test is Performed A blood sample ... person has ever been infected with oral or genital herpes . It looks for antibodies to herpes simplex virus ...

  10. Genital Herpes

    Science.gov (United States)

    ... can be can be considerable embarrassment, shame, and stigma associated with a herpes diagnosis that can substantially ... can be passed from mother to child during pregnancy or childbirth, or babies may be infected shortly ...

  11. Herpes viral culture of lesion

    Science.gov (United States)

    ... to confirm herpes infection. Herpes simplex virus causes genital herpes . It can also cause cold sores of the ... infection with herpes simplex virus. Herpes infections include genital herpes , cold sores on the lips or in the ...

  12. Nasal and skin delivery of IC31(®)-adjuvanted recombinant HSV-2 gD protein confers protection against genital herpes.

    Science.gov (United States)

    Wizel, Benjamin; Persson, Josefine; Thörn, Karolina; Nagy, Eszter; Harandi, Ali M

    2012-06-19

    Genital herpes caused by herpes simplex virus type 2 (HSV-2) remains the leading cause of genital ulcers worldwide. Given the disappointing results of the recent genital herpes vaccine trials in humans, development of novel vaccine strategies capable of eliciting protective mucosal and systemic immune responses to HSV-2 is urgently required. Here we tested the ability of the adjuvant IC31(®) in combination with HSV-2 glycoprotein D (gD) used through intranasal (i.n.), intradermal (i.d.), or subcutaneous (s.c.) immunization routes for induction of protective immunity against genital herpes infection in C57BL/6 mice. Immunization with gD plus IC31(®) through all three routes of immunization developed elevated gD-specific serum antibody responses with HSV-2 neutralizing activity. Whereas the skin routes promoted the induction of a mixed IgG2c/IgG1 isotype profile, the i.n. route only elicited IgG1 antibodies. All immunization routes were able to induce gD-specific IgG antibody responses in the vaginas of mice immunized with IC31(®)-adjuvanted gD. Although specific lymphoproliferative responses were observed in splenocytes from mice of most groups vaccinated with IC31(®)-adjuvanted gD, only i.d. immunization resulted in a significant splenic IFN-γ response. Further, immunization with gD plus IC31(®) conferred 80-100% protection against an otherwise lethal vaginal HSV-2 challenge with amelioration of viral replication and disease severity in the vagina. These results warrant further exploration of IC31(®) for induction of protective immunity against genital herpes and other sexually transmitted infections. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Bioinformatic Analysis of Gene Sets Regulated by Ligand-Activated and Dominant-Negative PPARγ in Mouse Aorta

    Science.gov (United States)

    Keen, Henry L.; Halabi, Carmen M.; Beyer, Andreas M.; de Lange, Willem J.; Liu, Xuebo; Maeda, Nobuyo; Faraci, Frank M.; Casavant, Thomas L.; Sigmund, Curt D.

    2010-01-01

    Objective Drugs that activate PPARγ improve glucose sensitivity and lower blood pressure, whereas dominant negative mutations in PPARγ cause severe insulin resistance and hypertension. We hypothesize that these PPARγ mutants regulate target genes opposite to that of ligand-mediated activation and tested this hypothesis on a genome-wide scale. Methods and Results We integrated gene expression data in aorta from mice treated with the PPARγ ligand rosiglitazone with data from mice containing a globally expressed knockin of the PPARγ P465L dominant negative mutation. We also integrated our data with publicly available datasets containing 1) gene expression profiles in many human tissues, 2) PPARγ target genes in 3T3-L1 adipocytes, and 3) experimentally validated PPARγ binding sites throughout the genome. Many classical PPARγ target genes were induced by rosiglitazone and repressed by dominant-negative PPARγ. A similar pattern was observed for about 90% of the gene sets regulated both by rosiglitazone and dominant-negative PPARγ. Genes exhibiting this pattern of contrasting regulation were significantly enriched for nearby PPARγ binding sites. Conclusions These results provide convincing evidence that the PPARγ P465L mutation causes transcriptional effects that are opposite to those mediated by PPARγ ligand thus validating mice carrying the mutation as a model of PPARγ interference. PMID:20018933

  14. Genital Herpes

    Science.gov (United States)

    ... best way to prevent genital herpes is abstinence. Teens who do have sex must properly use a latex condom every time ... reviewed: February 2016 More on this topic for: ... I Find Out If My Boyfriend Has an STD Before We Have Sex? Telling Your Partner You Have an STD View ...

  15. Tyrosine agonists reverse the molecular defects associated with dominant-negative mutations in human peroxisome proliferator-activated receptor gamma.

    Science.gov (United States)

    Agostini, Maura; Gurnell, Mark; Savage, David B; Wood, Emily M; Smith, Aaron G; Rajanayagam, Odelia; Garnes, Keith T; Levinson, Sidney H; Xu, H Eric; Schwabe, John W R; Willson, Timothy M; O'Rahilly, Stephen; Chatterjee, V Krishna

    2004-04-01

    Loss-of-function mutations in the ligand-binding domain of human peroxisome proliferator-activated receptor gamma (PPARgamma) are associated with a novel syndrome characterized by partial lipodystrophy and severe insulin resistance. Here we have further characterized the properties of natural dominant-negative PPARgamma mutants (P467L, V290M) and evaluated the efficacy of putative natural ligands and synthetic thiazolidinedione (TZD) or tyrosine-based (TA) receptor agonists in rescuing mutant receptor function. A range of natural ligands failed to activate the PPARgamma mutants and their transcriptional responses to TZDs (e.g. pioglitazone, rosiglitazone) were markedly attenuated, whereas TAs (e.g. farglitazar) corrected defects in ligand binding and coactivator recruitment by the PPARgamma mutants, restoring transcriptional function comparable with wild-type receptor. Transcriptional silencing via recruitment of corepressor contributes to dominant-negative inhibition of wild type by the P467L and V290M mutants and the introduction of an artificial mutation (L318A) disrupting corepressor interaction abrogated their dominant-negative activity. More complete ligand-dependent corepressor release and reversal of dominant-negative inhibition was achieved with TA than TZD agonists. Modeling suggests a structural basis for these observations: both mutations destabilize helix 12 to favor receptor-corepressor interaction; conversely, farglitazar makes more extensive contacts than rosiglitazone within the ligand-binding pocket, to stabilize helix 12, facilitating corepressor release and transcriptional activation. Farglitazar was a more potent inducer of PPARgamma target gene (aP2) expression in peripheral blood mononuclear cells with the P467L mutation. Having shown that rosiglitazone is of variable and limited efficacy in these subjects, we suggest that TAs may represent a more rational therapeutic approach.

  16. Neonatal herpes simplex pneumonia.

    OpenAIRE

    Lissauer, T J; Shaw, P J; Underhill, G

    1984-01-01

    A neonate with herpes simplex pneumonia is described. Herpes simplex infection should be considered in the differential diagnosis of pneumonia in newborn infants, even in the absence of clinically apparent herpes in the mother.

  17. Junction region of EWS-FLI1 fusion protein has a dominant negative effect in Ewing’s Sarcoma in vitro

    International Nuclear Information System (INIS)

    Jully, Babu; Vijayalakshmi, Ramshankar; Gopal, Gopisetty; Sabitha, Kesavan; Rajkumar, Thangarajan

    2012-01-01

    Ewing’s sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor. In the present study, we have further characterized the junction region of the EWS-FLI1 fusion protein. In-silico model of EWS-FLI1 fusion protein was analysed for ligand binding sites, and a putative region (amino acid (aa) 251–343 of the type 1 fusion protein) in the vicinity of the fusion junction was cloned and expressed using bacterial expression. The recombinant protein was characterized by Circular Dichroism (CD). We then expressed aa 251–280 ectopically in Ewing’s sarcoma cell-line and its effect on cell proliferation, tumorigenicity and expression of EWS-FLI1 target genes were analysed. Our modelling analysis indicated that Junction region (aa 251–343) encompasses potential ligand biding sites in the EWS-FLI1 protein and when expressed in bacteria was present as soluble form. Ectopically expressing this region in Ewing’s sarcoma cells inhibited tumorigenicity, and EWS-FLI1 target genes indicating a dominant negative biological effect. Junction region can be exploited further as target for drug development in future to specifically target EWS-FLI1 in Ewing’s Sarcoma

  18. Splice variants of the forkhead box protein AFX exhibit dominant negative activity and inhibit AFXalpha-mediated tumor cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Eun Jig Lee

    2008-07-01

    Full Text Available Loss-of-function in the apoptosis-inducing genes is known to facilitate tumorigenesis. AFX (FOXO4, a member of forkhead transcription factors functions as a tumor suppressor and has 2 isoforms, AFXalpha (505 a.a. and AFXzeta (450 a.a.. In human cancer cells, we identified an N-terminally deleted form of AFXalpha (alpha198-505, translated from a downstream start and 2 short N-terminal AFX proteins (90, and 101 a.a. produced by aberrant splicing.We investigated the expression and role of these AFX variants. Cell transduction study revealed that short N-terminal AFX proteins were not stable. Though alpha(198-505 protein expression was detected in the cytoplasm and nucleus, alpha(198-505 expressing cells did not show a nucleocytoplasmic shuttling mediated by PI3 kinase signaling. Whereas, we observed this shuttling in cells expressing either AFXalpha or AFXzeta protein. AFXzeta and alpha(198-505 lost the ability to transactivate BCL6 or suppress cyclin D2 gene expression. These variants did not induce cancer cell death whereas AFXalpha resulted in apoptosis. We found that AFXzeta and alpha(198-505 suppress the AFXalpha stimulation of BCL6 promoter in a dose dependent manner, indicating dominant negative activity. These variants also inhibited AFXalpha induction of apoptosis.Loss of function by aberrant splicing and the dominant negative activity of AFX variants may provide a mechanism for enhanced survival of neoplastic cells.

  19. attG and attC mutations of Agrobacterium tumefaciens are dominant negative mutations that block attachment and virulence.

    Science.gov (United States)

    Matthysse, Ann G; Jaeckel, Peter; Jeter, Cecelia

    2008-04-01

    The cryptic plasmid (pAT) of Agrobacterium tumefaciens was not required for virulence or attachment to plant surfaces. However, mutations in the attC and attG genes located on pAT caused the bacteria to become avirulent and non-attaching on tomato, carrot, and Bryophyllum daigremontiana. This was the case whether the mutation was in the copy of the genes located on pAT or whether it was carried in a second copy of the attA-G operon located on a plasmid in cells that contained a wild-type copy of pAT. Thus attC and attG mutations are dominant negative mutations. The mechanism by which these mutations block attachment and virulence is unknown.

  20. Expression of a dominant negative CELF protein in vivo leads to altered muscle organization, fiber size, and subtype.

    Directory of Open Access Journals (Sweden)

    Dara S Berger

    2011-04-01

    Full Text Available CUG-BP and ETR-3-like factor (CELF proteins regulate tissue- and developmental stage-specific alternative splicing in striated muscle. We previously demonstrated that heart muscle-specific expression of a nuclear dominant negative CELF protein in transgenic mice (MHC-CELFΔ effectively disrupts endogenous CELF activity in the heart in vivo, resulting in impaired cardiac function. In this study, transgenic mice that express the dominant negative protein under a skeletal muscle-specific promoter (Myo-CELFΔ were generated to investigate the role of CELF-mediated alternative splicing programs in normal skeletal muscle.Myo-CELFΔ mice exhibit modest changes in CELF-mediated alternative splicing in skeletal muscle, accompanied by a reduction of endomysial and perimysial spaces, an increase in fiber size variability, and an increase in slow twitch muscle fibers. Weight gain and mean body weight, total number of muscle fibers, and overall muscle strength were not affected.Although these findings demonstrate that CELF activity contributes to the normal alternative splicing of a subset of muscle transcripts in vivo, the mildness of the effects in Myo-CELFΔ muscles compared to those in MHC-CELFΔ hearts suggests CELF activity may be less determinative for alternative splicing in skeletal muscle than in heart muscle. Nonetheless, even these small changes in CELF-mediated splicing regulation were sufficient to alter muscle organization and muscle fiber properties affected in myotonic dystrophy. This lends further evidence to the hypothesis that dysregulation of CELF-mediated alternative splicing programs may be responsible for the disruption of these properties during muscle pathogenesis.

  1. Radiosensitization of head/neck squamous cell carcinoma by adenovirus-mediated expression of dominant negative constructs of the Nbs1 protein

    International Nuclear Information System (INIS)

    Carney, J.P.; Rhee, J.G.; Li, D.; Chen, T.; Suntharalingam, M.; O'Malley, B.W.

    2001-01-01

    . Conclusion: Dominant negative constructs of the Nbs1 protein are able to sensitize cells to ionizing radiation exposure. Surprisingly expression of the full-length Nbs1 protein results in enhanced sensitivity as well. These results provide a proof of principle that disruption of Nbs1 function may provide a means of enhancing the radiosensitivity of head and neck tumors

  2. Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types.

    Science.gov (United States)

    Villani, Rehan; Hodgson, Samantha; Legrand, Julien; Greaney, Jessica; Wong, Ho Yi; Pichol-Thievend, Cathy; Adolphe, Christelle; Wainwight, Brandon; Francois, Mathias; Khosrotehrani, Kiarash

    2017-05-15

    SOX family proteins SOX2 and SOX18 have been reported as being essential in determining hair follicle type; however, the role they play during development remains unclear. Here, we demonstrate that Sox18 regulates the normal differentiation of the dermal papilla of all hair types. In guard (primary) hair dermal condensate (DC) cells, we identified transient Sox18 in addition to SOX2 expression at E14.5, which allowed fate tracing of primary DC cells until birth. Similarly, expression of Sox18 was detected in the DC cells of secondary hairs at E16.5 and in tertiary hair at E18.5. Dominant-negative Sox18 mutation (opposum) did not prevent DC formation in any hair type. However, it affected dermal papilla differentiation, restricting hair formation especially in secondary and tertiary hairs. This Sox18 mutation also prevented neonatal dermal cells or dermal papilla spheres from inducing hair in regeneration assays. Microarray expression studies identified WNT5A and TNC as potential downstream effectors of SOX18 that are important for epidermal WNT signalling. In conclusion, SOX18 acts as a mesenchymal molecular switch necessary for the formation and function of the dermal papilla in all hair types. © 2017. Published by The Company of Biologists Ltd.

  3. Herpes Zoster Oticus

    Science.gov (United States)

    ... Page You are here Home » Disorders » All Disorders Herpes Zoster Oticus Information Page Herpes Zoster Oticus Information Page What research is being ... neurotropic viruses and development of neurological diseases including herpes simplex and varicella-zoster viruses. × What research is ...

  4. Increased adipogenesis in cultured embryonic chondrocytes and in adult bone marrow of dominant negative Erg transgenic mice.

    Directory of Open Access Journals (Sweden)

    Sébastien Flajollet

    Full Text Available In monolayer culture, primary articular chondrocytes have an intrinsic tendency to lose their phenotype during expansion. The molecular events underlying this chondrocyte dedifferentiation are still largely unknown. Several transcription factors are important for chondrocyte differentiation. The Ets transcription factor family may be involved in skeletal development. One family member, the Erg gene, is mainly expressed during cartilage formation. To further investigate the potential role of Erg in the maintenance of the chondrocyte phenotype, we isolated and cultured chondrocytes from the rib cartilage of embryos of transgenic mice that express a dominant negative form of Erg (DN-Erg during cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days did not affect the early dedifferentiation usually observed in cultured chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes, suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray, validated by quantitative RT-PCR, revealed strong differential gene expression, with a decrease in chondrogenesis-related markers and an increase in adipogenesis-related gene expression in cultured DN-Erg chondrocytes. These results indicate that Erg is involved in either maintaining the chondrogenic phenotype in vitro or in cell fate orientation. Along with the in vitro studies, we compared adipocyte presence in wild-type and transgenic mice skeletons. Histological investigations revealed an increase in the number of adipocytes in the bone marrow of adult DN-Erg mice even though no adipocytes were detected in embryonic cartilage or bone. These findings suggest that the Ets transcription factor family may contribute to the homeostatic balance in skeleton cell plasticity.

  5. Dilated cardiomyopathy mutations in δ-sarcoglycan exert a dominant-negative effect on cardiac myocyte mechanical stability.

    Science.gov (United States)

    Campbell, Matthew D; Witcher, Marc; Gopal, Anoop; Michele, Daniel E

    2016-05-01

    Delta-sarcoglycan is a component of the sarcoglycan subcomplex within the dystrophin-glycoprotein complex located at the plasma membrane of muscle cells. While recessive mutations in δ-sarcoglycan cause limb girdle muscular dystrophy 2F, dominant mutations in δ-sarcoglycan have been linked to inherited dilated cardiomyopathy (DCM). The purpose of this study was to investigate functional cellular defects present in adult cardiac myocytes expressing mutant δ-sarcoglycans harboring the dominant inherited DCM mutations R71T or R97Q. This study demonstrates that DCM mutant δ-sarcoglycans can be stably expressed in adult rat cardiac myocytes and traffic similarly to wild-type δ-sarcoglycan to the plasma membrane, without perturbing assembly of the dystrophin-glycoprotein complex. However, expression of DCM mutant δ-sarcoglycan in adult rat cardiac myocytes is sufficient to alter cardiac myocyte plasma membrane stability in the presence of mechanical strain. Upon cyclical cell stretching, cardiac myocytes expressing mutant δ-sarcoglycan R97Q or R71T have increased cell-impermeant dye uptake and undergo contractures at greater frequencies than myocytes expressing normal δ-sarcoglycan. Additionally, the R71T mutation creates an ectopic N-linked glycosylation site that results in aberrant glycosylation of the extracellular domain of δ-sarcoglycan. Therefore, appropriate glycosylation of δ-sarcoglycan may also be necessary for proper δ-sarcoglycan function and overall dystrophin-glycoprotein complex function. These studies demonstrate that DCM mutations in δ-sarcoglycan can exert a dominant negative effect on dystrophin-glycoprotein complex function leading to myocardial mechanical instability that may underlie the pathogenesis of δ-sarcoglycan-associated DCM. Copyright © 2016 the American Physiological Society.

  6. A novel de novo dominant negative mutation in DNM1L impairs mitochondrial fission and presents as childhood epileptic encephalopathy.

    Science.gov (United States)

    Fahrner, Jill A; Liu, Raymond; Perry, Michael Scott; Klein, Jessica; Chan, David C

    2016-08-01

    DNM1L encodes dynamin-related protein 1 (DRP1/DLP1), a key component of the mitochondrial fission machinery that is essential for proper functioning of the mammalian brain. Previously reported probands with de novo missense mutations in DNM1L presented in the first year of life with severe encephalopathy and refractory epilepsy, with several dying within the first several weeks after birth. In contrast, we report identical novel missense mutations in DNM1L in two unrelated probands who experienced normal development for several years before presenting with refractory focal status epilepticus and subsequent rapid neurological decline. We expand the phenotype of DNM1L-related mitochondrial fission defects, reveal common unique clinical characteristics and imaging findings, and compare the cellular impact of this novel mutation to the previously reported A395D lethal variant. We demonstrate that our R403C mutation, which resides in the assembly region of DRP1, acts by a dominant-negative mechanism and reduces oligomerization, mitochondrial fission activity, and mitochondrial recruitment of DRP1, but to a lesser extent compared to the A395D mutation. In contrast to the initial report of neonatal lethality resulting from DNM1L mutation and DRP1 dysfunction, our results show that milder DRP1 impairment is compatible with normal early development and subsequently results in a distinct set of neurological findings. In addition, we identify a common pathogenic mechanism whereby DNM1L mutations impair mitochondrial fission. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Herpes Zoster

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    Hamid Ehsani-Nia

    2017-04-01

    Full Text Available History of present illness: A 26-year-old male presented to the emergency department with a burning rash over his left axilla and chest that started 2 days prior to presentation. The pain had been steadily worsening and was exacerbated by touch and the rubbing of his clothes over it. Patient denied fevers, chills, or weakness. Patient denied any past medical history, past surgical history or medications. He was unsure of his vaccination history and endorsed having chicken pox as a child. Significant findings: The patient was in mild distress, afebrile, with stable vital signs. His physical exam revealed an erythematous, grouped vesicular rash in various stages of progression including erythematous papules, clear vesicles, and pustular vesicles. Few lesions were scabbed over. No signs of crusting or scarring were appreciated. The distribution encompassed the entire left T4 dermatome both posteriorly and anteriorly. No other rashes were appreciated elsewhere on the body. Discussion: Herpes Zoster (HZ, also known as “shingles,” is a result of the reactivation Varicella Zoster Virus (VZV that emerges from latency in the sensory dorsal root ganglion. The reactivation causes the spreading of a classic rash of group vesicular lesions in various stages along the unilateral sensory dermatomal distribution over the first 3 days. Ulceration and crusting begin to occur after 3-5 days.1 The diagnosis is usually made clinically; however PCR testing of skin lesions is also available to differentiate between VZV, HSV1, and HSV2.2 The incidence of HZ increases with age due to immunosenesacence of cell mediated immunity, with the mean age between 43 and 53 years old.3 An immunocompromised state, due to factors like human immunodeficiency virus (HIV, medications, and autoimmune disease, also increases the incidence of HZ.4-6 A routine HIV screening in this patient was negative. He was prescribed oral acyclovir 800 mg, five times per day for five days.

  8. Targeting the Genital Tract Mucosa with a Lipopeptide/Recombinant Adenovirus Prime/Boost Vaccine Induces Potent and Long-Lasting CD8+ T Cell Immunity Against Herpes: Importance of Myeloid Differentiation Factor 881

    Science.gov (United States)

    Zhang, Xiuli; Dervillez, Xavier; Chentoufi, Aziz Alami; Badakhshan, Tina; Bettahi, Ilham; BenMohamed, Lbachir

    2012-01-01

    Targeting the mucosal immune system of the genital tract (GT) with subunit vaccines failed to induce potent and durable local CD8+ T cell immunity, crucial for protection against many sexually transmitted viral (STV) pathogens, including herpes simplex virus type 2 (HSV-2) that causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8+ T cell immunity to protect the female genital tract from herpes. The lipopeptide and the rAdv5 vaccine express the immunodominant HSV-2 CD8+ T cell epitope (gB498-505) and both were delivered intravaginally (IVAG) in the progesterone-induced B6 mouse model of genital herpes. Compared to its homologous lipopeptide/lipopeptide (Lipo/Lipo); the Lipo/rAdv5 prime/boost immunized mice: (i) developed potent and sustained HSV-specific CD8+ T cells, detected in both the GT draining nodes (GT-DLN) and in the vaginal mucosa (VM); (ii) had significantly lower virus titers; (iii) had decreased overt signs of genital herpes disease; and (iv) did not succumb to lethal infection (p herpes infection and disease. PMID:23018456

  9. Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin

    Directory of Open Access Journals (Sweden)

    Slack Barbara E

    2011-05-01

    Full Text Available Abstract Background The amyloid precursor protein (APP is cleaved by β- and γ-secretases to generate toxic amyloid β (Aβ peptides. Alternatively, α-secretases cleave APP within the Aβ domain, precluding Aβ formation and releasing the soluble ectodomain, sAPPα. We previously showed that inhibition of the GTPase dynamin reduced APP internalization and increased release of sAPPα, apparently by prolonging the interaction between APP and α-secretases at the plasma membrane. This was accompanied by a reduction in Aβ generation. In the present study, we investigated whether surface expression of the α-secretase ADAM (a disintegrin and metalloprotease10 is also regulated by dynamin-dependent endocytosis. Results Transfection of human embryonic kidney (HEK cells stably expressing M3 muscarinic receptors with a dominant negative dynamin I mutant (dyn I K44A, increased surface expression of both immature, and mature, catalytically active forms of co-expressed ADAM10. Surface levels of ADAM10 were unaffected by activation of protein kinase C (PKC or M3 receptors, indicating that receptor-coupled shedding of the ADAM substrate APP is unlikely to be mediated by inhibition of ADAM10 endocytosis in this cell line. Dyn I K44A strongly increased the formation of a C-terminal fragment of ADAM10, consistent with earlier reports that the ADAM10 ectodomain is itself a target for sheddases. The abundance of this fragment was increased in the presence of a γ-secretase inhibitor, but was not affected by M3 receptor activation. The dynamin mutant did not affect the distribution of ADAM10 and its C-terminal fragment between raft and non-raft membrane compartments. Conclusions Surface expression and limited proteolysis of ADAM10 are regulated by dynamin-dependent endocytosis, but are unaffected by activation of signaling pathways that upregulate shedding of ADAM substrates such as APP. Modulation of ADAM10 internalization could affect cellular behavior in two

  10. Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin.

    Science.gov (United States)

    Carey, Robyn M; Blusztajn, Jan K; Slack, Barbara E

    2011-05-17

    The amyloid precursor protein (APP) is cleaved by β- and γ-secretases to generate toxic amyloid β (Aβ) peptides. Alternatively, α-secretases cleave APP within the Aβ domain, precluding Aβ formation and releasing the soluble ectodomain, sAPPα. We previously showed that inhibition of the GTPase dynamin reduced APP internalization and increased release of sAPPα, apparently by prolonging the interaction between APP and α-secretases at the plasma membrane. This was accompanied by a reduction in Aβ generation. In the present study, we investigated whether surface expression of the α-secretase ADAM (a disintegrin and metalloprotease)10 is also regulated by dynamin-dependent endocytosis. Transfection of human embryonic kidney (HEK) cells stably expressing M3 muscarinic receptors with a dominant negative dynamin I mutant (dyn I K44A), increased surface expression of both immature, and mature, catalytically active forms of co-expressed ADAM10. Surface levels of ADAM10 were unaffected by activation of protein kinase C (PKC) or M3 receptors, indicating that receptor-coupled shedding of the ADAM substrate APP is unlikely to be mediated by inhibition of ADAM10 endocytosis in this cell line. Dyn I K44A strongly increased the formation of a C-terminal fragment of ADAM10, consistent with earlier reports that the ADAM10 ectodomain is itself a target for sheddases. The abundance of this fragment was increased in the presence of a γ-secretase inhibitor, but was not affected by M3 receptor activation. The dynamin mutant did not affect the distribution of ADAM10 and its C-terminal fragment between raft and non-raft membrane compartments. Surface expression and limited proteolysis of ADAM10 are regulated by dynamin-dependent endocytosis, but are unaffected by activation of signaling pathways that upregulate shedding of ADAM substrates such as APP. Modulation of ADAM10 internalization could affect cellular behavior in two ways: by altering the putative signaling activity of

  11. In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress.

    Directory of Open Access Journals (Sweden)

    Blair R Anderson

    2015-07-01

    Full Text Available African Americans have a disproportionate risk for developing nephropathy. This disparity has been attributed to coding variants (G1 and G2 in apolipoprotein L1 (APOL1; however, there is little functional evidence supporting the role of this protein in renal function. Here, we combined genetics and in vivo modeling to examine the role of apol1 in glomerular development and pronephric filtration and to test the pathogenic potential of APOL1 G1 and G2. Translational suppression or CRISPR/Cas9 genome editing of apol1 in zebrafish embryos results in podocyte loss and glomerular filtration defects. Complementation of apol1 morphants with wild-type human APOL1 mRNA rescues these defects. However, the APOL1 G1 risk allele does not ameliorate defects caused by apol1 suppression and the pathogenicity is conferred by the cis effect of both individual variants of the G1 risk haplotype (I384M/S342G. In vivo complementation studies of the G2 risk allele also indicate that the variant is deleterious to protein function. Moreover, APOL1 G2, but not G1, expression alone promotes developmental kidney defects, suggesting a possible dominant-negative effect of the altered protein. In sickle cell disease (SCD patients, we reported previously a genetic interaction between APOL1 and MYH9. Testing this interaction in vivo by co-suppressing both transcripts yielded no additive effects. However, upon genetic or chemical induction of anemia, we observed a significantly exacerbated nephropathy phenotype. Furthermore, concordant with the genetic interaction observed in SCD patients, APOL1 G2 reduces myh9 expression in vivo, suggesting a possible interaction between the altered APOL1 and myh9. Our data indicate a critical role for APOL1 in renal function that is compromised by nephropathy-risk encoding variants. Moreover, our interaction studies indicate that the MYH9 locus is also relevant to the phenotype in a stressed microenvironment and suggest that consideration of

  12. [Anti-HBV effects of genetically engineered replication-defective HBV with combined expression of antisense RNA and dominant negative mutants of core protein and construction of first-generation packaging cell line for HBV vector].

    Science.gov (United States)

    Sun, Dian Xing; Hu, Da Rong; Wu, Guang Hui; Hu, Xue Ling; Li, Juan; Fan, Gong Ren

    2002-08-01

    To explore the possibility of using HBV as a gene delivery vector, and to test the anti-HBV effects by intracellular combined expression of antisense RNA and dominant negative mutants of core protein. Full length of mutant HBV genome, which expresses core-partial P fusion protein and/or antisense RNA, was transfected into HepG2.2.15 cell lines. Positive clones were selected and mixed in respective groups with hygromycin in the culture medium. HBsAg and HBeAg, which exist in the culture medium, were tested by ELISA method. Intracellular HBc related HBV DNA was examined by dot blot hybridization. The existence of recombinant HBV virion in the culture medium was examined by PCR. Free of packaging signal, HBV genome, which express the HBV structural proteins including core, pol and preS/S proteins, was inserted into pCI-neo vector. HepG2 cell lines were employed to transfect with the construct. G418 selection was done at the concentration of 400mug/ml in the culture medium. The G418-resistant clones with the best expression of HBsAg and HBcAg were theoretically considered as packaging cell lines and propagated under the same conditions. It was transfected with plasmid pMEP-CPAS and then selected with G418 and hygromycin in the culture medium. The existence of recombinant HBV virion in the culture medium was examined by PCR. The mean inhibitory rates of HBsAg were 2.74% 3.83%, 40.08 2.05% (t=35.5, PDNA were 0, 82.0%, 59.9%, and 96.6%, respectively. Recombinant HB virion was detectable in the culture medium of all the three treatment groups. G418-resistant HBV packaging cell line, which harbored an HBV mutant whose packaging signal had been deleted, was generated. Expression of HBsAg and HBcAg was detectable. Transfected with plasmid pMEP-CPAS, it was found to secrete recombinant HB virion and no wild-type HBV was detectable in the culture medium. It has stronger anti-HBV effects by combined expression of antisense RNA and dominant negative mutants than by individual

  13. Differential in situ hybridization for herpes simplex virus typing in routine skin biopsies

    NARCIS (Netherlands)

    Botma, H. J.; Dekker, H.; van Amstel, P.; Cairo, I.; van den Berg, F. M.

    1995-01-01

    A herpes simplex virus (HSV) type 2 specific recombinant plasmid probe designated pH2S3 was constructed from non-HSV-1 crossreactive regions of the HSV-2 genome. DNA in situ hybridization on in vitro reconstructed tissue samples of sheep collagen matrix impregnated with herpes virus-infected human

  14. Dominant negative mutant of ionotropic glutamate receptor subunit GluR3: implications for the role of a cysteine residue for its channel activity and pharmacological properties.

    Science.gov (United States)

    Watase, K; Sekiguchi, M; Matsui, T A; Tagawa, Y; Wada, K

    1997-01-01

    We reported that a 33-amino-acid deletion (from tyrosine-715 to glycine-747) in a putative extracellular loop of GluR3 produced a mutant that exhibited dominant negative effects upon the functional expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [Sekiguchi et al. (1994) J. Biol. Chem. 269, 14559-14565]. In this study, we searched for a key residue in the dominant negative effects to explore the mechanism and examined the role of the residue in the function of the AMPA receptor. We prepared 20 GluR3 mutants with amino acid substitutions within the 33-amino-acid-region, and dominant negative effects were tested electrophysiologically in Xenopus oocytes co-expressing the mutant and normal subunits. Among the mutants, only a GluR3 mutant in which an original cysteine (Cys)-722 was replaced by alanine exhibited a dominant negative effect comparable with that of the original mutant in which the entire 33-amino-acid segment is deleted. The co-expression of the Cys-722 mutant did not inhibit the translation of normal subunits in oocytes. The Cys-722 mutant formed a functional homomeric receptor with significantly higher affinity for glutamate or kainate than a homomeric GluR3 receptor. The Cys-722 mutation greatly enhanced the sensitivity of GluR3 for aniracetam, which alters kinetic properties of AMPA receptors. The kainate-induced currents in oocytes expressing the Cys-722 mutant alone showed strong inward rectification. These results suggest that the Cys-722 in GluR3 is important for dominant negative effects and plays a crucial role in the determination of pharmacological properties in AMPA receptor function. PMID:9065754

  15. Targeting the genital tract mucosa with a lipopeptide/recombinant adenovirus prime/boost vaccine induces potent and long-lasting CD8+ T cell immunity against herpes: importance of MyD88.

    Science.gov (United States)

    Zhang, Xiuli; Dervillez, Xavier; Chentoufi, Aziz Alami; Badakhshan, Tina; Bettahi, Ilham; Benmohamed, Lbachir

    2012-11-01

    Targeting of the mucosal immune system of the genital tract with subunit vaccines has failed to induce potent and durable local CD8(+) T cell immunity, which is crucial for protection against many sexually transmitted viral pathogens, including HSV type 2 (HSV-2), which causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8(+) T cell immunity to protect the female genital tract from herpes. The lipopeptide vaccine and the rAdv5 vaccine express the immunodominant HSV-2 CD8(+) T cell epitope (gB(498-505)), and both were delivered intravaginally in the progesterone-induced B6 mouse model of genital herpes. Compared with mice immunized with the homologous lipopeptide/lipopeptide (Lipo/Lipo) vaccine, the Lipo/rAdv5 prime/boost immunized mice 1) developed potent and sustained HSV-specific CD8(+) T cells, detected in both the genital tract draining nodes and in the vaginal mucosa; 2) had significantly lower virus titers; 3) had decreased overt signs of genital herpes disease; and 4) did not succumb to lethal infection (p herpes infection and disease.

  16. Dominant negative selection of vaccinia virus using a thymidine kinase/thymidylate kinase fusion gene and the prodrug azidothymidine

    International Nuclear Information System (INIS)

    Holzer, Georg W.; Mayrhofer, Josef; Gritschenberger, Werner; Falkner, Falko G.

    2005-01-01

    The Escherichia coli thymidine kinase/thymidylate kinase (tk/tmk) fusion gene encodes an enzyme that efficiently converts the prodrug 3'-azido-2',3'-dideoxythymidine (AZT) into its toxic triphosphate derivative, a substance which stops DNA chain elongation. Integration of this marker gene into vaccinia virus that normally is not inhibited by AZT allowed the establishment of a powerful selection procedure for recombinant viruses. In contrast to the conventional vaccinia thymidine kinase (tk) selection that is performed in tk-negative cell lines, AZT selection can be performed in normal (tk-positive) cell lines. The technique is especially useful for the generation of replication-deficient vaccinia viruses and may also be used for gene knock-out studies of essential vaccinia genes

  17. Dominant negative mutants of Bacillus thuringiensis Cry1Ab toxin function as anti-toxins: demonstration of the role of oligomerization in toxicity.

    Directory of Open Access Journals (Sweden)

    Claudia Rodríguez-Almazán

    Full Text Available Bacillus thuringiensis Cry toxins, that are used worldwide in insect control, kill insects by a mechanism that depends on their ability to form oligomeric pores that insert into the insect-midgut cells. These toxins are being used worldwide in transgenic plants or spray to control insect pests in agriculture. However, a major concern has been the possible effects of these insecticidal proteins on non-target organisms mainly in ecosystems adjacent to agricultural fields.We isolated and characterized 11 non-toxic mutants of Cry1Ab toxin affected in different steps of the mechanism of action namely binding to receptors, oligomerization and pore-formation. These mutant toxins were analyzed for their capacity to block wild type toxin activity, presenting a dominant negative phenotype. The dominant negative phenotype was analyzed at two levels, in vivo by toxicity bioassays against susceptible Manduca sexta larvae and in vitro by pore formation activity in black lipid bilayers. We demonstrate that some mutations located in helix alpha-4 completely block the wild type toxin activity at sub-stoichiometric level confirming a dominant negative phenotype, thereby functioning as potent antitoxins.This is the first reported case of a Cry toxin dominant inhibitor. These data demonstrate that oligomerization is a fundamental step in Cry toxin action and represent a potential mechanism to protect special ecosystems from the possible effect of Cry toxins on non-target organisms.

  18. Herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Bakken, J.S.; Camenga, D.L.; Glazier, M.C.; Coughlan, J.D.

    1989-01-01

    Early institution of therapy with acyclovir is essential for the successful outcome in herpes simplex encephalitis. Brain biopsy remains the only conclusive means of establishing the diagnosis, but many fear possible biobsy complications. Thus, therapy is often instituted when the diagnosis is clinically suspected, even though cerebral computed tomography and other diagnostic studies may be inconclusive. Nuclear magnetic resonance imaging (NMR) has proven to be a sensitive tool for diagnosing presumptive herpes simplex encephalitis. This case presentation demonstrates the superiority of cerebral NMR over computerized tomography for detecting early temporal lobe changes consistent with acute herpes simplex encephalitis

  19. Herpes Labialis: An Update.

    Science.gov (United States)

    Leung, Alexander K C; Barankin, Benjamin

    2017-01-01

    Herpes labialis is characterized by recurrent vesicular eruptions primarily on the lips and perioral skin. The condition is contagious, can cause significant discomfort/pain, and can have an adverse effect on the quality of life. To update the evaluation and treatment of herpes labialis. A PubMed search was completed in Clinical Queries using the key term "herpes labialis". Patents were searched using the key term "herpes labialis" from www.freepatentsonline.com. The diagnosis of herpes labialis is mainly clinical based on classic grouped lesions (papules, vesicles, ulcers) on the lip. Antiviral therapy shortens the duration of pain and discomfort, hastens healing, and reduces viral shedding. Thus, episodic treatment is warranted, especially if the patient desires treatment for cosmetic purposes or for relief of pain. Such treatment needs to be initiated promptly, ideally in the prodromal stage and no later than 48 hours from the onset of lesions to achieve optimal results. Chronic suppressive therapy with oral antiviral agents should be considered for patients with severe or frequent (six or more episodes per year) recurrences. Recent patents related to the management of herpes labialis are also discussed. For episodic treatment, oral antiviral agents, such as acyclovir (Zovirax), valacyclovir (Valtrex) and famciclovir (Famvir), are superior to topical antiviral therapy. Valacyclovir and famciclovir have greater oral bioavailability and are better absorbed than acyclovir, require less frequent dosing, but are more expensive and are not approved for children. Topical antiviral agents such as 5% acyclovir cream/ointment (Zovirax) ± hydrocortisone (Xerese), 1% penciclovir (Denavir) cream, and 50 mg Buccal Adhesive Tablet (ABT-50 mg) can also be used for episodic treatment of herpes labialis. These topical agents are not effective in the prevention of recurrent herpes labialis. For chronic daily suppressive therapy, oral antivirals are the treatment of choice

  20. Regulation of hippocampal synaptic plasticity thresholds and changes in exploratory and learning behavior in dominant negative NPR-B mutant rats

    Directory of Open Access Journals (Sweden)

    Gleb eBarmashenko

    2014-12-01

    Full Text Available The second messenger cyclic GMP affects synaptic transmission and modulates synaptic plasticity and certain types of learning and memory processes. The impact of the natriuretic peptide receptor B (NPR-B and its ligand C-type natriuretic peptide (CNP, one of several cGMP producing signalling systems, on hippocampal synaptic plasticity and learning is, however, less well understood. We have previously shown that the NPR-B ligand CNP increases the magnitude of long-term depression (LTD in hippocampal area CA1, while reducing the induction of long-term potentiation (LTP. We have extended this line of research to show that bidirectional plasticity is affected in the opposite way in rats expressing a dominant-negative mutant of NPR-B (NSE-NPR-BdeltaKC lacking the intracellular guanylyl cyclase domain under control of a promoter for neuron-specific enolase. The brain cells of these transgenic rats express functional dimers of the NPR-B receptor containing the dominant-negative NPR-BdeltaKC mutant, and therefore show decreased CNP-stimulated cGMP-production in brain membranes. The NPR-B transgenic rats display enhanced LTP but reduced LTD in hippocampal slices. When the frequency-dependence of synaptic modification to afferent stimulation in the range of 1-100 Hz was assessed in transgenic rats the threshold for LTP induction was raised, but LTD induction was facilitated. In parallel, NPR-BdeltaKC rats exhibited an enhancement in exploratory and learning behavior. These results indicate that bidirectional plasticity and learning and memory mechanism are affected in transgenic rats expressing a dominant-negative mutant of NPR-B. Our data substantiate the hypothesis that NPR-B-dependent cGMP signalling has a modulatory role for synaptic information storage and learning.

  1. Mitochondrial Dysfunction Contributes to Impaired Insulin Secretion in INS-1 Cells with Dominant-negative Mutations of HNF-1α and in HNF-1α-deficient Islets*

    OpenAIRE

    Pongratz, Rebecca L.; Kibbey, Richard G.; Kirkpatrick, Clare L.; Zhao, Xiaojian; Pontoglio, Marco; Yaniv, Moshe; Wollheim, Claes B.; Shulman, Gerald I.; Cline, Gary W.

    2009-01-01

    Maturity Onset Diabetes of the Young-type 3 (MODY-3) has been linked to mutations in the transcription factor hepatic nuclear factor (HNF)-1α, resulting in deficiency in glucose-stimulated insulin secretion. In INS-1 cells overexpressing doxycycline-inducible HNF-1α dominant-negative (DN-) gene mutations, and islets from Hnf-1α knock-out mice, insulin secretion was impaired in response to glucose (15 mm) and other nutrient secretagogues. Decreased rates of insulin secretion in response to glu...

  2. Herpes zoster (shingles) disseminated (image)

    Science.gov (United States)

    Herpes zoster (shingles) normally occurs in a limited area that follows a dermatome (see the "dermatome" picture). In individuals with damaged immune systems, herpes zoster may be widespread (disseminated), causing serious illness. ...

  3. Herpes Simplex Virus (Cold Sores)

    Science.gov (United States)

    ... Print Share Cold Sores in Children: About the Herpes Simplex Virus Page Content ​A child's toddler and ... Cold sores (also called fever blisters or oral herpes) start as small blisters that form around the ...

  4. Radiation therapy and herpes zoster

    International Nuclear Information System (INIS)

    Kaneko, Itsuo; Matsushima, Hideno; Yamada, Teruyo; Moriya, Hiroshi

    1975-01-01

    The relationship between herpes zoster and radiation therapy was discussed and the combination of herpes zoster with malignancies was observed. Reported were five cases of herpes zoster (four breast and one lung carcinoma) out of 317 cases of malignancies which were irradiated in our clinic and include considerations about the etiologic relationship. (J.P.N.)

  5. Genital herpes - self-care

    Science.gov (United States)

    Herpes - genital - self-care; Herpes simplex - genital - self-care; Herpesvirus 2 - self-care; HSV-2 - self-care ... One type of herpes virus stays in the body by hiding within nerve cells. It can remain "asleep" (dormant) for a long time. ...

  6. Cochlear outer hair cells in a dominant-negative connexin26 mutant mouse preserve non-linear capacitance in spite of impaired distortion product otoacoustic emission.

    Science.gov (United States)

    Minekawa, A; Abe, T; Inoshita, A; Iizuka, T; Kakehata, S; Narui, Y; Koike, T; Kamiya, K; Okamura, H-O; Shinkawa, H; Ikeda, K

    2009-12-15

    Mutations in the connexin26 gene (GJB2) are the most common genetic cause of congenital bilateral non-syndromic sensorineural hearing loss. Transgenic mice were established carrying human Cx26 with the R75W mutation that was identified in a deaf family with autosomal dominant negative inheritance [Kudo T et al. (2003) Hum Mol Genet 12:995-1004]. A dominant-negative Gjb2 R75W transgenic mouse model shows incomplete development of the cochlear supporting cells, resulting in profound deafness from birth [Inoshita A et al. (2008) Neuroscience 156:1039-1047]. The Cx26 defect in the Gjb2 R75W transgenic mouse is restricted to the supporting cells; it is unclear why the auditory response is severely disturbed in spite of the presence of outer hair cells (OHCs). The present study was designed to evaluate developmental changes in the in vivo and in vitro function of the OHC, and the fine structure of the OHC and adjacent supporting cells in the R75W transgenic mouse. No detectable distortion product otoacoustic emissions were observed at any frequencies in R75W transgenic mice throughout development. A characteristic phenotype observed in these mice was the absence of the tunnel of Corti, Nuel's space, and spaces surrounding the OHC; the OHC were compressed and squeezed by the surrounding supporting cells. On the other hand, the OHC developed normally. Structural features of the lateral wall, such as the membrane-bound subsurface cisterna beneath the plasma membrane, were intact. Prestin, the voltage-dependent motor protein, was observed by immunohistochemistry in the OHC basolateral membranes of both transgenic and non-transgenic mice. No significant differences in electromotility of isolated OHCs during development was observed between transgenic and control mice. The present study indicates that normal development of the supporting cells is indispensable for proper cellular function of the OHC.

  7. Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome.

    Science.gov (United States)

    Chiarelli, Nicola; Carini, Giulia; Zoppi, Nicoletta; Ritelli, Marco; Colombi, Marina

    2018-01-01

    Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM) organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition into the ECM of

  8. Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome.

    Directory of Open Access Journals (Sweden)

    Nicola Chiarelli

    Full Text Available Vascular Ehlers-Danlos syndrome (vEDS is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII, which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures. To shed lights into molecular mechanisms underlying vEDS, we performed gene expression profiling in cultured skin fibroblasts from three patients with different structural COL3A1 mutations. Transcriptome analysis revealed significant changes in the expression levels of several genes involved in maintenance of cell redox and endoplasmic reticulum (ER homeostasis, COLLs folding and extracellular matrix (ECM organization, formation of the proteasome complex, and cell cycle regulation. Protein analyses showed that aberrant COLLIII expression is associated with the disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and elastin, as well as with the reduction of the proteoglycans perlecan, decorin, and versican, all playing an important role in the vascular system. Furthermore, the altered distribution of the ER marker protein disulfide isomerase PDI and the strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the disturbance of ER-related homeostasis and COLLs biosynthesis and post-translational modifications, indicated by microarray analysis. Our findings add new insights into the pathophysiology of this severe vascular disorder, since they provide a picture of the gene expression changes in vEDS skin fibroblasts and highlight that dominant negative mutations in COL3A1 also affect post-translational modifications and deposition

  9. Demonstration of differential quantitative requirements for NSF among multiple vesicle fusion pathways of GLUT4 using a dominant-negative ATPase-deficient NSF

    International Nuclear Information System (INIS)

    Chen Xiaoli; Matsumoto, Hideko; Hinck, Cynthia S.; Al-Hasani, Hadi; St-Denis, Jean-Francois; Whiteheart, Sidney W.; Cushman, Samuel W.

    2005-01-01

    In this study, we investigated the relative participation of N-ethylmaleimide-sensitive factor (NSF) in vivo in a complex multistep vesicle trafficking system, the translocation response of GLUT4 to insulin in rat adipose cells. Transfections of rat adipose cells demonstrate that over-expression of wild-type NSF has no effect on total, or basal and insulin-stimulated cell-surface expression of HA-tagged GLUT4. In contrast, a dominant-negative NSF (NSF-D1EQ) can be expressed at a low enough level that it has little effect on total HA-GLUT4, but does reduce both basal and insulin-stimulated cell-surface HA-GLUT4 by ∼50% without affecting the GLUT4 fold-translocation response to insulin. However, high expression levels of NSF-D1EQ decrease total HA-GLUT4. The inhibitory effect of NSF-D1EQ on cell-surface HA-GLUT4 is reversed when endocytosis is inhibited by co-expression of a dominant-negative dynamin (dynamin-K44A). Moreover, NSF-D1EQ does not affect cell-surface levels of constitutively recycling GLUT1 and TfR, suggesting a predominant effect of low-level NSF-D1EQ on the trafficking of GLUT4 from the endocytic recycling compared to the intracellular GLUT4-specific compartment. Thus, our data demonstrate that the multiple fusion steps in GLUT4 trafficking have differential quantitative requirements for NSF activity. This indicates that the rates of plasma and intracellular membrane fusion reactions vary, leading to differential needs for the turnover of the SNARE proteins

  10. Herpes zoster during pregnancy

    OpenAIRE

    Pupco, Anna; Bozzo, Pina; Koren, Gideon

    2011-01-01

    Question One of my pregnant patients, a 32-year-old woman (gravida 2, para 1), has a flare up of herpes zoster (HZ) at the T11 to T12 dermatomes. This virus, the varicella-zoster virus, causes chickenpox, which can be teratogenic. Is this also true for HZ?

  11. Genital Herpes: A Review.

    Science.gov (United States)

    Groves, Mary Jo

    2016-06-01

    Genital herpes is a common sexually transmitted disease, affecting more than 400 million persons worldwide. It is caused by herpes simplex virus (HSV) and characterized by lifelong infection and periodic reactivation. A visible outbreak consists of single or clustered vesicles on the genitalia, perineum, buttocks, upper thighs, or perianal areas that ulcerate before resolving. Symptoms of primary infection may include malaise, fever, or localized adenopathy. Subsequent outbreaks, caused by reactivation of latent virus, are usually milder. Asymptomatic shedding of transmissible virus is common. Although HSV-1 and HSV-2 are indistinguishable visually, they exhibit differences in behavior that may affect management. Patients with HSV-2 have a higher risk of acquiring human immunodeficiency virus (HIV) infection. Polymerase chain reaction assay is the preferred method of confirming HSV infection in patients with active lesions. Treatment of primary and subsequent outbreaks with nucleoside analogues is well tolerated and reduces duration, severity, and frequency of recurrences. In patients with HSV who are HIV-negative, treatment reduces transmission of HSV to uninfected partners. During pregnancy, antiviral prophylaxis with acyclovir is recommended from 36 weeks of gestation until delivery in women with a history of genital herpes. Elective cesarean delivery should be performed in laboring patients with active lesions to reduce the risk of neonatal herpes.

  12. Herpes simplex-encefalitis

    DEFF Research Database (Denmark)

    Jørgensen, Laura Krogh; Mogensen, Trine Hyrup

    2017-01-01

    Herpes simplex encephalitis (HSE) is a rare disease, although it is the most common form of sporadic encephalitis worldwide. Recently, studies have provided important new insight into the genetic and immunological basis of HSE. However, even in the presence of antiviral treatment, mortality...

  13. Herpes Simplex Virus

    Science.gov (United States)

    Khoddami, Maliheh; Nadji, Seyed Alireza; Dehghanian, Paria

    2017-01-01

    Langerhans cell histiocytosis (LCH) is a rare histiocytic proliferative disorder of unknown etiology and mainly affects young children. The histological feature is granuloma-like proliferation of langerhans-type dendritic cells. Although the possible role of viruses such as Epstein-Barr virus ( EBV , Human Herpes virus -4 ), Human Herpes virus-6 ( HHV-6 ), Herpes Simplex virus ( HSV ) types 1 and 2 and Cytomegalovirus (CMV, Human Herpes virus-5 ) is suggested in the pathogenesis of LCH by some investigators, its exact pathophysiology has not been cleared yet. In this study, we investigated the presence of HSV types 1 and 2 in Iranian children with LCH. In this retrospective study, we investigated the prevalence of presence of HSV types 1 and 2 (in 30 patients with LCH), using paraffin-embedded tissue samples and 30 age and tissue-matched controls (operated for reasons other than infectious diseases) from the Department of Pediatric Pathology, Tehran, Iran, by nested Polymerase Chain reaction method. No ethical issues arose in the study, because only the pathology reports were reviewed and patients were anonymous. We failed to find HSV types 1 and 2 DNA in any of the 30 patients with LCH or the control group. According to our findings, HSV types 1 and 2 do not appear to have any etiologic role in the pathogenesis of LCH in Iranian children. These results are in accordance with previous investigations with negative findings.

  14. A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.

    Science.gov (United States)

    Khare, Swati; Nick, Jerelyn A; Zhang, Yalan; Galeano, Kira; Butler, Brittany; Khoshbouei, Habibeh; Rayaprolu, Sruti; Hathorn, Tyisha; Ranum, Laura P W; Smithson, Lisa; Golde, Todd E; Paucar, Martin; Morse, Richard; Raff, Michael; Simon, Julie; Nordenskjöld, Magnus; Wirdefeldt, Karin; Rincon-Limas, Diego E; Lewis, Jada; Kaczmarek, Leonard K; Fernandez-Funez, Pedro; Nick, Harry S; Waters, Michael F

    2017-01-01

    The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of

  15. A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Muneaki, E-mail: muneaki@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 (Japan); Nara, Takeshi, E-mail: tnara@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 (Japan); Enomoto, Masahiro, E-mail: menomoto@uhnres.utoronto.ca [Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, 351-0198 (Japan); Princess Margaret Cancer Centre, Department of Medical Biophysics, University of Toronto, M5G1L7, Toronto, Ontario (Canada); Kurebayashi, Nagomi, E-mail: nagomik@juntendo.ac.jp [Department of Pharmacology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, 113-8421 (Japan); Yoshida, Mitsutaka, E-mail: myoshida@juntendo.ac.jp [Laboratoly of Morphology and Image Analysis, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 (Japan); Sakurai, Takashi, E-mail: tsakurai@juntendo.ac.jp [Department of Pharmacology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, 113-8421 (Japan); Mita, Toshihiro, E-mail: tmita@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 (Japan); Mikoshiba, Katsuhiko, E-mail: mikosiba@brain.riken.jp [Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, 351-0198 (Japan); Calcium Oscillation Project, International Cooperative Research Project and Solution-Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama, 332-0012 (Japan)

    2015-10-23

    Inositol 1,4,5-trisphosphate receptor (IP{sub 3}R) is a key regulator of intracellular Ca{sup 2+} concentration that release Ca{sup 2+} from Ca{sup 2+} stores in response to various external stimuli. IP{sub 3}R also works as a signal hub which form a platform for interacting with various proteins involved in diverse cell signaling. Previously, we have identified an IP{sub 3}R homolog in the parasitic protist, Trypanosoma cruzi (TcIP{sub 3}R). Parasites expressing reduced or increased levels of TcIP{sub 3}R displayed defects in growth, transformation, and infectivity. In the present study, we established parasitic strains expressing a dominant negative form of TcIP{sub 3}R, named DN-TcIP{sub 3}R, to further investigate the physiological role(s) of TcIP{sub 3}R. We found that the growth of epimastigotes expressing DN-TcIP{sub 3}R was significantly slower than that of parasites with TcIP{sub 3}R expression levels that were approximately 65% of wild-type levels. The expression of DN-TcIP{sub 3}R in epimastigotes induced metacyclogenesis even in the normal growth medium. Furthermore, these epimastigotes showed the presence of dense mitochondria under a transmission electron microscope. Our findings confirm that TcIP{sub 3}R is crucial for epimastigote growth, as previously reported. They also suggest that a strong inhibition of the IP{sub 3}R-mediated signaling induces metacyclogenesis and that mitochondrial integrity is closely associated with this signaling. - Highlights: • We established T. cruzi strains expressing a dominant negative form of the TcIP{sub 3}R. • DN-TcIP{sub 3}R expression inhibits epimastigote growth and induces metacyclogenesis. • Microscopic analysis indicated TcIP{sub 3}R role in maintaining mitochondrial integrity. • Growth, but not microbial density, was altered by mammalian IP{sub 3}R inhibitor (2-APB).

  16. Polyethyleneimine mediated DNA transfection in schistosome parasites and regulation of the WNT signaling pathway by a dominant-negative SmMef2.

    Directory of Open Access Journals (Sweden)

    Shuang Liang

    Full Text Available Schistosomiasis is a serious global problem and the second most devastating parasitic disease following malaria. Parasitic worms of the genus Schistosoma are the causative agents of schistosomiasis and infect more than 240 million people worldwide. The paucity of molecular tools to manipulate schistosome gene expression has made an understanding of genetic pathways in these parasites difficult, increasing the challenge of identifying new potential drugs for treatment. Here, we describe the use of a formulation of polyethyleneimine (PEI as an alternative to electroporation for the efficacious transfection of genetic material into schistosome parasites. We show efficient expression of genes from a heterologous CMV promoter and from the schistosome Sm23 promoter. Using the schistosome myocyte enhancer factor 2 (SmMef2, a transcriptional activator critical for myogenesis and other developmental pathways, we describe the development of a dominant-negative form of the schistosome Mef2. Using this mutant, we provide evidence that SmMef2 may regulate genes in the WNT pathway. We also show that SmMef2 regulates its own expression levels. These data demonstrate the use of PEI to facilitate effective transfection of nucleic acids into schistosomes, aiding in the study of schistosome gene expression and regulation, and development of genetic tools for the characterization of molecular pathways in these parasites.

  17. A Dominant Negative OsKAT2 Mutant Delays Light-Induced Stomatal Opening and Improves Drought Tolerance without Yield Penalty in Rice.

    Science.gov (United States)

    Moon, Seok-Jun; Kim, Hyun Y; Hwang, Hyunsik; Kim, Jin-Ae; Lee, Yongsang; Min, Myung K; Yoon, In S; Kwon, Taek-Ryoun; Kim, Beom-Gi

    2017-01-01

    Stomata are the main gateways for water and air transport between leaves and the environment. Inward-rectifying potassium channels regulate photo-induced stomatal opening. Rice contains three inward rectifying shaker-like potassium channel proteins, OsKAT1, OsKAT2, and OsKAT3. Among these, only OsKAT2 is specifically expressed in guard cells. Here, we investigated the functions of OsKAT2 in stomatal regulation using three dominant negative mutant proteins, OsKAT2(T235R), OsKAT2(T285A) and OsKAT2(T285D), which are altered in amino acids in the channel pore and at a phosphorylation site. Yeast complementation and patch clamp assays showed that all three mutant proteins lost channel activity. However, among plants overexpressing these mutant proteins, only plants overexpressing OsKAT2(T235R) showed significantly less water loss than the control. Moreover, overexpression of this mutant protein led to delayed photo-induced stomatal opening and increased drought tolerance. Our results indicate that OsKAT2 is an inward- rectifying shaker-like potassium channel that mainly functions in stomatal opening. Interestingly, overexpression of OsKAT2(T235R) did not cause serious defects in growth or yield in rice, suggesting that OsKAT2 is a potential target for engineering plants with improved drought tolerance without yield penalty.

  18. A Dominant Negative OsKAT2 Mutant Delays Light-Induced Stomatal Opening and Improves Drought Tolerance without Yield Penalty in Rice

    Directory of Open Access Journals (Sweden)

    Seok-Jun Moon

    2017-05-01

    Full Text Available Stomata are the main gateways for water and air transport between leaves and the environment. Inward-rectifying potassium channels regulate photo-induced stomatal opening. Rice contains three inward rectifying shaker-like potassium channel proteins, OsKAT1, OsKAT2, and OsKAT3. Among these, only OsKAT2 is specifically expressed in guard cells. Here, we investigated the functions of OsKAT2 in stomatal regulation using three dominant negative mutant proteins, OsKAT2(T235R, OsKAT2(T285A and OsKAT2(T285D, which are altered in amino acids in the channel pore and at a phosphorylation site. Yeast complementation and patch clamp assays showed that all three mutant proteins lost channel activity. However, among plants overexpressing these mutant proteins, only plants overexpressing OsKAT2(T235R showed significantly less water loss than the control. Moreover, overexpression of this mutant protein led to delayed photo-induced stomatal opening and increased drought tolerance. Our results indicate that OsKAT2 is an inward- rectifying shaker-like potassium channel that mainly functions in stomatal opening. Interestingly, overexpression of OsKAT2(T235R did not cause serious defects in growth or yield in rice, suggesting that OsKAT2 is a potential target for engineering plants with improved drought tolerance without yield penalty.

  19. The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism.

    Directory of Open Access Journals (Sweden)

    Chunxing Yang

    2010-12-01

    Full Text Available TAR DNA binding protein 43 KD (TDP-43 is an essential gene that regulates gene transcription, mRNA splicing and stability. In amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD, two fatal neurodegenerative diseases, TDP-43 is fragmented, generating multiple fragments that include the C-terminal fragment of ∼25 KD. The role of these fragments in the pathogenesis of ALS and FTD is not clear. Here we investigated the aggregation propensity in various polypeptide regions of TDP-43 in mammalian cells and the effect of these fragments on cultured neurons. By expressing the full length and various TDP-43 fragments in motor neuron-derived NSC-34 cells and primary neurons, we found that both N- and C-terminal fragments of TDP-43 are prone to aggregate and the C-terminal end of RRM2 region is required, though not sufficient, for aggregation. The aggregation of the TDP-43 fragments can drive co-aggregation with the full-length TDP-43, consequently reducing the nuclear TDP-43. In addition, the TDP-43 fragments can impair neurite growth during neuronal differentiation. Importantly, overexpression of the full-length TDP-43 rescues the neurite growth phenotype whereas knockdown of the endogenous TDP-43 reproduces this phenotype. These results suggest that TDP-43 fragments, particularly the pathologically relevant C-terminal fragments, can impair neuronal differentiation by dominant-negatively interfering with the function of the full length TDP-43, thus playing a role in pathogenesis in ALS and FTD.

  20. Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Junjie; Bulek, Katarzyna; Gulen, Muhammet F; Zepp, Jarod A; Karagkounis, Georgio; Martin, Bradley N; Zhou, Hao; Yu, Minjia; Liu, Xiuli; Huang, Emina; Fox, Paul L; Kalady, Matthew F; Markowitz, Sanford D; Li, Xiaoxia

    2015-12-01

    Single immunoglobulin and toll-interleukin 1 receptor (SIGIRR), a negative regulator of the Toll-like and interleukin-1 receptor (IL-1R) signaling pathways, controls intestinal inflammation and suppresses colon tumorigenesis in mice. However, the importance of SIGIRR in human colorectal cancer development has not been determined. We investigated the role of SIGIRR in development of human colorectal cancer. We performed RNA sequence analyses of pairs of colon tumor and nontumor tissues, each collected from 68 patients. Immunoblot and immunofluorescence analyses were used to determine levels of SIGIRR protein in primary human colonic epithelial cells, tumor tissues, and colon cancer cell lines. We expressed SIGIRR and mutant forms of the protein in Vaco cell lines. We created and analyzed mice that expressed full-length (control) or a mutant form of Sigirr (encoding SIGIRR(N86/102S), which is not glycosylated) specifically in the intestinal epithelium. Some mice were given azoxymethane (AOM) and dextran sulfate sodium to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by immunohistochemical and gene expression profile analyses. RNA sequence analyses revealed increased expression of a SIGIRR mRNA isoform, SIGIRR(ΔE8), in colorectal cancer tissues compared to paired nontumor tissues. SIGIRR(ΔE8) is not modified by complex glycans and is therefore retained in the cytoplasm-it cannot localize to the cell membrane or reduce IL1R signaling. SIGIRR(ΔE8) interacts with and has a dominant-negative effect on SIGIRR, reducing its glycosylation, localization to the cell surface, and function. Most SIGIRR detected in human colon cancer tissues was cytoplasmic, whereas in nontumor tissues it was found at the cell membrane. Mice that expressed SIGIRR(N86/102S) developed more inflammation and formed larger tumors after administration of azoxymethane and dextran sulfate sodium than control mice; colon tissues from these mutant mice expressed

  1. A dominant-negative mutation of mouse Lmx1b causes glaucoma and is semi-lethal via LDB1-mediated dimerization [corrected].

    Directory of Open Access Journals (Sweden)

    Sally H Cross

    2014-05-01

    Full Text Available Mutations in the LIM-homeodomain transcription factor LMX1B cause nail-patella syndrome, an autosomal dominant pleiotrophic human disorder in which nail, patella and elbow dysplasia is associated with other skeletal abnormalities and variably nephropathy and glaucoma. It is thought to be a haploinsufficient disorder. Studies in the mouse have shown that during development Lmx1b controls limb dorsal-ventral patterning and is also required for kidney and eye development, midbrain-hindbrain boundary establishment and the specification of specific neuronal subtypes. Mice completely deficient for Lmx1b die at birth. In contrast to the situation in humans, heterozygous null mice do not have a mutant phenotype. Here we report a novel mouse mutant Icst, an N-ethyl-N-nitrosourea-induced missense substitution, V265D, in the homeodomain of LMX1B that abolishes DNA binding and thereby the ability to transactivate other genes. Although the homozygous phenotypic consequences of Icst and the null allele of Lmx1b are the same, heterozygous Icst elicits a phenotype whilst the null allele does not. Heterozygous Icst causes glaucomatous eye defects and is semi-lethal, probably due to kidney failure. We show that the null phenotype is rescued more effectively by an Lmx1b transgene than is Icst. Co-immunoprecipitation experiments show that both wild-type and Icst LMX1B are found in complexes with LIM domain binding protein 1 (LDB1, resulting in lower levels of functional LMX1B in Icst heterozygotes than null heterozygotes. We conclude that Icst is a dominant-negative allele of Lmx1b. These findings indicate a reassessment of whether nail-patella syndrome is always haploinsufficient. Furthermore, Icst is a rare example of a model of human glaucoma caused by mutation of the same gene in humans and mice.

  2. Endogenous interleukin-22 protects against inflammatory bowel disease but not autoimmune cholangitis in dominant negative form of transforming growth factor beta receptor type II mice.

    Science.gov (United States)

    Yang, G-X; Sun, Y; Tsuneyama, K; Zhang, W; Leung, P S C; He, X-S; Ansari, A A; Bowlus, C; Ridgway, W M; Gershwin, M E

    2016-08-01

    During chronic inflammation, interleukin (IL)-22 expression is up-regulated in both CD4 and CD8 T cells, exerting a protective role in infections. However, in autoimmunity, IL-22 appears to have either a protective or a pathogenic role in a variety of murine models of autoimmunity and, by extrapolation, in humans. It is not clear whether IL-22 itself mediates inflammation or is a by-product of inflammation. We have taken advantage of the dominant negative form of transforming growth factor beta receptor type II (dnTGF-βRII) mice that develop both inflammatory bowel disease and autoimmune cholangitis and studied the role and the biological function of IL-22 by generating IL-22(-/-) dnTGF-βRII mice. Our data suggest that the influence of IL-22 on autoimmunity is determined in part by the local microenvironment. In particular, IL-22 deficiency exacerbates tissue injury in inflammatory bowel disease, but has no influence on either the hepatocytes or cholangiocytes in the same model. These data take on particular significance in the previously defined effects of IL-17A, IL-12p40 and IL-23p19 deficiency and emphasize that, in colitis, there is a dominant role of IL-23/T helper type 17 (Th17) signalling. Furthermore, the levels of IL-22 are IL-23-dependent. The use of cytokine therapy in patients with autoimmune disease has significant potential, but must take into account the overlapping and often promiscuous effects that can theoretically exacerbate inflammation. © 2016 British Society for Immunology.

  3. Mitochondrial Dysfunction Contributes to Impaired Insulin Secretion in INS-1 Cells with Dominant-negative Mutations of HNF-1α and in HNF-1α-deficient Islets*

    Science.gov (United States)

    Pongratz, Rebecca L.; Kibbey, Richard G.; Kirkpatrick, Clare L.; Zhao, Xiaojian; Pontoglio, Marco; Yaniv, Moshe; Wollheim, Claes B.; Shulman, Gerald I.; Cline, Gary W.

    2009-01-01

    Maturity Onset Diabetes of the Young-type 3 (MODY-3) has been linked to mutations in the transcription factor hepatic nuclear factor (HNF)-1α, resulting in deficiency in glucose-stimulated insulin secretion. In INS-1 cells overexpressing doxycycline-inducible HNF-1α dominant-negative (DN-) gene mutations, and islets from Hnf-1α knock-out mice, insulin secretion was impaired in response to glucose (15 mm) and other nutrient secretagogues. Decreased rates of insulin secretion in response to glutamine plus leucine and to methyl pyruvate, but not potassium depolarization, indicate defects specific to mitochondrial metabolism. To identify the biochemical mechanisms responsible for impaired insulin secretion, we used 31P NMR measured mitochondrial ATP synthesis (distinct from glycolytic ATP synthesis) together with oxygen consumption measurements to determine the efficiency of mitochondrial oxidative phosphorylation. Mitochondrial uncoupling was significantly higher in DN-HNF-1α cells, such that rates of ATP synthesis were decreased by approximately one-half in response to the secretagogues glucose, glutamine plus leucine, or pyruvate. In addition to closure of the ATP-sensitive K+ channels with mitochondrial ATP synthesis, mitochondrial production of second messengers through increased anaplerotic flux has been shown to be critical for coupling metabolism to insulin secretion. 13C-Isotopomer analysis and tandem mass spectrometry measurement of Krebs cycle intermediates revealed a negative impact of DN-HNF-1α and Hnf-1α knock-out on mitochondrial second messenger production with glucose but not amino acids. Taken together, these results indicate that, in addition to reduced glycolytic flux, uncoupling of mitochondrial oxidative phosphorylation contributes to impaired nutrient-stimulated insulin secretion with either mutations or loss of HNF-1α. PMID:19376774

  4. Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.

    Science.gov (United States)

    Zhang, Hua; Chen, Hongsheng; Luo, Hunjin; An, Jing; Sun, Lin; Mei, Lingyun; He, Chufeng; Jiang, Lu; Jiang, Wen; Xia, Kun; Li, Jia-Da; Feng, Yong

    2012-03-01

    Waardenburg syndrome (WS) is an auditory-pigmentary disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. PAX3 and SOX10 are two transcription factors that can activate the expression of microphthalmia-associated transcription factor (MITF), a critical transcription factor for melanocyte development. Mutations of PAX3 are associated with WS1 and WS3, while mutations of SOX10 cause WS2 and WS4. Recently, we identified some novel WS-associated mutations in PAX3 and SOX10 in a cohort of Chinese WS patients. Here, we further identified an E248fsX30 SOX10 mutation in a family of WS2. We analyzed the subcellular distribution, expression and in vitro activity of two PAX3 mutations (p.H80D, p.H186fsX5) and four SOX10 mutations (p.E248fsX30, p.G37fsX58, p.G38fsX69 and p.R43X). Except H80D PAX3, which retained partial activity, the other mutants were unable to activate MITF promoter. The H80D PAX3 and E248fsX30 SOX10 were localized in the nucleus as wild type (WT) proteins, whereas the other mutant proteins were distributed in both cytoplasm and nucleus. Furthermore, E248fsX30 SOX10 protein retained the DNA-binding activity and showed dominant-negative effect on WT SOX10. However, E248fsX30 SOX10 protein seems to decay faster than the WT one, which may underlie the mild WS2 phenotype caused by this mutation.

  5. An engineered transforming growth factor β (TGF-β) monomer that functions as a dominant negative to block TGF-β signaling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Kyung; Barron, Lindsey; Hinck, Cynthia S.; Petrunak, Elyse M.; Cano, Kristin E.; Thangirala, Avinash; Iskra, Brian; Brothers, Molly; Vonberg, Machell; Leal, Belinda; Richter, Blair; Kodali, Ravindra; Taylor, Alexander B.; Du, Shoucheng; Barnes, Christopher O.; Sulea, Traian; Calero, Guillermo; Hart, P. John; Hart, Matthew J.; Demeler, Borries; Hinck, Andrew P. (Texas-HSC); (NRCC); (Pitt)

    2017-02-22

    The transforming growth factor β isoforms, TGF-β1, -β2, and -β3, are small secreted homodimeric signaling proteins with essential roles in regulating the adaptive immune system and maintaining the extracellular matrix. However, dysregulation of the TGF-β pathway is responsible for promoting the progression of several human diseases, including cancer and fibrosis. Despite the known importance of TGF-βs in promoting disease progression, no inhibitors have been approved for use in humans. Herein, we describe an engineered TGF-β monomer, lacking the heel helix, a structural motif essential for binding the TGF-β type I receptor (TβRI) but dispensable for binding the other receptor required for TGF-β signaling, the TGF-β type II receptor (TβRII), as an alternative therapeutic modality for blocking TGF-β signaling in humans. As shown through binding studies and crystallography, the engineered monomer retained the same overall structure of native TGF-β monomers and bound TβRII in an identical manner. Cell-based luciferase assays showed that the engineered monomer functioned as a dominant negative to inhibit TGF-β signaling with a Ki of 20–70 nM. Investigation of the mechanism showed that the high affinity of the engineered monomer for TβRII, coupled with its reduced ability to non-covalently dimerize and its inability to bind and recruit TβRI, enabled it to bind endogenous TβRII but prevented it from binding and recruiting TβRI to form a signaling complex. Such engineered monomers provide a new avenue to probe and manipulate TGF-β signaling and may inform similar modifications of other TGF-β family members.

  6. A spontaneous dominant-negative mutation within a 35S::AtMYB90 transgene inhibits flower pigment production in tobacco.

    Science.gov (United States)

    Velten, Jeff; Cakir, Cahid; Cazzonelli, Christopher I

    2010-03-29

    In part due to the ease of visual detection of phenotypic changes, anthocyanin pigment production has long been the target of genetic and molecular research in plants. Specific members of the large family of plant myb transcription factors have been found to play critical roles in regulating expression of anthocyanin biosynthetic genes and these genes continue to serve as important tools in dissecting the molecular mechanisms of plant gene regulation. A spontaneous mutation within the coding region of an Arabidopsis 35S::AtMYB90 transgene converted the activator of plant-wide anthocyanin production to a dominant-negative allele (PG-1) that inhibits normal pigment production within tobacco petals. Sequence analysis identified a single base change that created a premature nonsense codon, truncating the encoded myb protein. The resulting mutant protein lacks 78 amino acids from the wild type C-terminus and was confirmed as the source of the white-flower phenotype. A putative tobacco homolog of AtMYB90 (NtAN2) was isolated and found to be expressed in flower petals but not leaves of all tobacco plants tested. Using transgenic tobacco constitutively expressing the NtAN2 gene confirmed the NtAN2 protein as the likely target of PG-1-based inhibition of tobacco pigment production. Messenger RNA and anthocyanin analysis of PG-1Sh transgenic lines (and PG-1Sh x purple 35S::NtAN2 seedlings) support a model in which the mutant myb transgene product acts as a competitive inhibitor of the native tobacco NtAN2 protein. This finding is important to researchers in the field of plant transcription factor analysis, representing a potential outcome for experiments analyzing in vivo protein function in test transgenic systems that over-express or mutate plant transcription factors.

  7. Chronic herpes simplex virus encephalitis in childhood.

    NARCIS (Netherlands)

    Leen, W.G.; Weemaes, C.M.R.; Verbeek, M.M.; Willemsen, M.A.A.P.; Rotteveel, J.J.

    2006-01-01

    Although herpes simplex virus is a major cause of acute encephalitis in childhood, chronic herpes simplex virus encephalitis has only rarely been reported. This report presents a case of chronic herpes simplex virus encephalitis in a 6-year-old female. Diagnosis was based on the detection of herpes

  8. Neonatal herpes in Denmark 1977-1991

    DEFF Research Database (Denmark)

    Fonnest, G; de la Fuente Fonnest, I; Weber, Tom

    1997-01-01

    BACKGROUND: To prevent neonatal herpes, women in labor with genital herpes infection are still delivered by Cesarean section. This policy is currently being debated. The aim of this study was to determine the incidence of neonatal herpes in Denmark and to evaluate the prevention practice. METHODS......: All newborns with perinatal herpes in Denmark 1977-1991 were identified from hospital-records. RESULTS: Of 862,298 deliveries 136 possible cases were found but only 30 (22%) fulfilled the criteria for neonatal herpes. The incidence increased from 2.36 to 4.56 per 100,000 live births during 1977......-1984 through 1984-1991. Three mothers (10%) had recurrent herpes at delivery, three (10%) had primary herpes, and five (17%) had oral herpes. Seven infants (23%) were delivered by Cesarean section. Nine (30%) only had cutaneous herpes, four (13%) had CNS herpes, nine (30%) had disseminated disease. Six (20...

  9. [Pain in herpes zoster: Prevention and treatment].

    Science.gov (United States)

    Calvo-Mosquera, G; González-Cal, A; Calvo-Rodríguez, D; Primucci, C Y; Plamenov-Dipchikov, P

    Shingles is a painful rash that results from reactivation of latent varicella-zoster virus in the dorsal root ganglia or cranial nerves. In this article an update is presented on the prevention and pharmacological treatment of the secondary pain from the virus infection. The most effective way to prevent post-herpetic neuralgia and its consequences is the prevention of herpes itself. A live attenuated vaccine (the Oka strain varicella zoster virus) has been available for several years, and is approved in adults aged 50 years old. Although this vaccine has shown to be effective against herpes zoster and post-herpetic neuralgia, its effectiveness decreases with age and is contraindicated in patients with some form of immunosuppression. Today the recombinant vaccines provide an alternative, and may be administered to immunocompromised persons. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Critical significance of the region between Helix 1 and 2 for efficient dominant-negative inhibition by conversion-incompetent prion protein.

    Directory of Open Access Journals (Sweden)

    Yuzuru Taguchi

    Full Text Available Prion diseases are fatal infectious neurodegenerative disorders in man and animals associated with the accumulation of the pathogenic isoform PrP(Sc of the host-encoded prion protein (PrP(c. A profound conformational change of PrP(c underlies formation of PrP(Sc and prion propagation involves conversion of PrP(c substrate by direct interaction with PrP(Sc template. Identifying the interfaces and modalities of inter-molecular interactions of PrPs will highly advance our understanding of prion propagation in particular and of prion-like mechanisms in general. To identify the region critical for inter-molecular interactions of PrP, we exploited here dominant-negative inhibition (DNI effects of conversion-incompetent, internally-deleted PrP (ΔPrP on co-expressed conversion-competent PrP. We created a series of ΔPrPs with different lengths of deletions in the region between first and second α-helix (H1∼H2 which was recently postulated to be of importance in prion species barrier and PrP fibril formation. As previously reported, ΔPrPs uniformly exhibited aberrant properties including detergent insolubility, limited protease digestion resistance, high-mannose type N-linked glycans, and intracellular localization. Although formerly controversial, we demonstrate here that ΔPrPs have a GPI anchor attached. Surprisingly, despite very similar biochemical and cell-biological properties, DNI efficiencies of ΔPrPs varied significantly, dependant on location and inversely correlated with the size of deletion. This data demonstrates that H1∼H2 and the region C-terminal to it are critically important for efficient DNI. It also suggests that this region is involved in PrP-PrP interaction and conversion of PrP(C into PrP(Sc. To reconcile the paradox of how an intracellular PrP can exert DNI, we demonstrate that ΔPrPs are subject to both proteasomal and lysosomal/autophagic degradation pathways. Using autophagy pathways ΔPrPs obtain access to the locale

  11. Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning.

    Science.gov (United States)

    Cortez, IbDanelo; Bulavin, Dmitry V; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

    2017-03-30

    A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α AF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α AF/+ ) and kinase activity. As a result, aged DN-p38α AF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer's disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual's relative risk. In the present study, we evaluated aged DN-p38α AF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38α AF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38α AF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38α AF/+ , we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38α AF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Heterozygous PINK1 p.G411S increases risk of Parkinson’s disease via a dominant-negative mechanism

    Science.gov (United States)

    Puschmann, Andreas; Fiesel, Fabienne C; Caulfield, Thomas R; Hudec, Roman; Ando, Maya; Truban, Dominika; Hou, Xu; Ogaki, Kotaro; Heckman, Michael G; James, Elle D; Swanberg, Maria; Jimenez-Ferrer, Itzia; Hansson, Oskar; Opala, Grzegorz; Siuda, Joanna; Boczarska-Jedynak, Magdalena; Friedman, Andrzej; Koziorowski, Dariusz; Rudzińska-Bar, Monika; Aasly, Jan O; Lynch, Timothy; Mellick, George D; Mohan, Megha; Silburn, Peter A; Sanotsky, Yanosh; Vilariño-Güell, Carles; Farrer, Matthew J; Chen, Li; Dawson, Valina L; Dawson, Ted M; Wszolek, Zbigniew K; Ross, Owen A; Springer, Wolfdieter

    2017-01-01

    size conferred by a partial dominant-negative function phenotype. PMID:27807026

  13. Analysis of contributions of herpes simplex virus type 1 UL43 protein ...

    African Journals Online (AJOL)

    Abstract. Purpose: To investigate whether UL43 protein, which is highly conserved in alpha- and gamma herpes viruses, and a non-glycosylated transmembrane protein, ... Generation of recombinant viruses. For generation of HSV-1 ΔUL43, the UL43 ORF was mutagenized with synthetic oligonucleotides. HUL43-MUT for ...

  14. Public TCR Use by Herpes Simplex Virus-2-Specific Human CD8 CTLs

    NARCIS (Netherlands)

    Dong, Lichun; Li, Penny; Oenema, Tjitske; McClurkan, Christopher L.; Koelle, David M.

    2010-01-01

    Recombination of germline TCR alpha and beta genes generates polypeptide receptors for MHC peptide. Ag exposure during long-term herpes simplex infections may shape the T cell repertoire over time. We investigated the CD8 T cell response to HSV-2 in chronically infected individuals by sequencing the

  15. Analysis of contributions of herpes simplex virus type 1 UL43 protein ...

    African Journals Online (AJOL)

    Purpose: To investigate whether UL43 protein, which is highly conserved in alpha- and gamma herpes viruses, and a non-glycosylated transmembrane protein, is involved in virus entry and virus-induced cell fusion. Methods: Mutagenesis was accomplished by a markerless two-step Red recombination mutagenesis system ...

  16. Generalized acute mucocutaneous herpes simplex

    Directory of Open Access Journals (Sweden)

    Mittal R

    1994-01-01

    Full Text Available A case of generalized acute mucocutaneous herpes simplex is reported in a 15 years old boy. There was neither underlying disease nor any evidence of genetic or acquired immune deficiency.

  17. Molecular diagnosis of visceral herpes zoster

    NARCIS (Netherlands)

    de Jong, M. D.; Weel, J. F.; van Oers, M. H.; Boom, R.; Wertheim-van Dillen, P. M.

    2001-01-01

    Patients with disseminated herpes zoster may present with severe abdominal pain that results from visceral involvement of varicella-zoster-virus infection. In the absence of cutaneous eruptions of herpes zoster, visceral herpes zoster is extremely difficult to diagnose. This diagnostic difficulty

  18. Detergent extraction of herpes simplex virus type 1 glycoprotein D by zwitterionic and non-ionic detergents and purification by ion-exchange high-performance liquid chromatography

    NARCIS (Netherlands)

    Welling-Wester, S; Feijlbrief, M; Koedijk, DGAM; Welling, GW

    1998-01-01

    Detergents (surfactants) are the key reagents in the extraction and purification of integral membrane proteins. Zwitterionic and non-ionic detergents were used for the extraction of recombinant glycoprotein D (gD-1) of herpes simplex virus type 1 (HSV-1) from insect cells infected with recombinant

  19. MRI of herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Demaerel, P.; Wilms, G.; Johannik, K.; Hecke, P. van; Baert, A.L.; Robberecht, W.; Carton, H.

    1992-01-01

    The magnetic resonance imaging (MRI) findings in eight patients with herpes simplex meningoence phalitis were reviewed: 14 examinations were analysed. The most striking finding was high signal intensity in the temporal lobe(s) with the typical configuration known from CT. Meningeal enhancement after Gd-DTPA administration was clearly seen in four patients. Haemorrhagic changes are much better seen on MRI than on CT. When adequate motion control can be achieved, MRI becomes the examination of choice in the diagnosis and follow-up of herpes simplex encephalitis. Localized 1 H MR spectroscopy also proved promising in the study of neuronal loss. (orig.)

  20. Current thinking on genital herpes.

    Science.gov (United States)

    Hofstetter, Annika M; Rosenthal, Susan L; Stanberry, Lawrence R

    2014-02-01

    Genital herpes has a high global prevalence and burden of disease. This manuscript highlights recent advances in our understanding of genital herpes simplex virus (HSV) infections. Studies demonstrate a changing epidemiological landscape with an increasing proportion of genital herpes cases associated with HSV type 1. There is also growing evidence that the majority of infected individuals exhibit frequent, brief shedding episodes that are most often asymptomatic, which likely contribute to high HSV transmission rates. Given this finding as well as readily available serological assays, some have proposed that routine HSV screening be performed; however, this remains controversial and is not currently recommended. Host immune responses, particularly local CD4 and CD8 T cell activity, are crucial for HSV control and clearance following initial infection, during latency and after reactivation. Prior HSV immunity may also afford partial protection against HSV reinfection and disease. Although HSV vaccine trials have been disappointing to date and existing antiviral medications are limited, novel prophylactic and therapeutic modalities are currently in development. Although much remains unknown about genital herpes, improved knowledge of HSV epidemiology, pathogenesis and host immunity may help guide new strategies for disease prevention and control.

  1. Construction of rat cell lines that contain potential morphologically transforming regions of the herpes simplex virus type 2 genome

    NARCIS (Netherlands)

    van den Berg, F. M.; van Amstel, P. J.; Walboomers, J. M.

    1985-01-01

    Hybrid recombinant plasmids were constructed; they were composed of the herpes simplex virus type 2 (HSV2) thymidine kinase (tk) gene and DNA sequences of HSV2 that have been reported to induce morphological and/or oncogenic transformation of rodent cells in culture. Several plasmids were made in

  2. Two step culture for production of recombinant herpes simplex virus ...

    African Journals Online (AJOL)

    ajl user 1

    Corning 500 mL disposable Erlenmeyer flasks were used with a working volume of 80 mL. After suspension in fresh Grace's insect medium, Sf9 cells were grown ... The glass bioreactor vessel consisted of a cylindrical body and a rounded bottom. Mixing was performed by an impeller with three blades rotating at the rate of ...

  3. Optimal management of genital herpes: current perspectives.

    Science.gov (United States)

    Sauerbrei, Andreas

    2016-01-01

    As one of the most common sexually transmitted diseases, genital herpes is a global medical problem with significant physical and psychological morbidity. Genital herpes is caused by herpes simplex virus type 1 or type 2 and can manifest as primary and/or recurrent infection. This manuscript provides an overview about the fundamental knowledge on the virus, its epidemiology, and infection. Furthermore, the current possibilities of antiviral therapeutic interventions and laboratory diagnosis of genital herpes as well as the present situation and perspectives for the treatment by novel antivirals and prevention of disease by vaccination are presented. Since the medical management of patients with genital herpes simplex virus infection is often unsatisfactory, this review aims at all physicians and health professionals who are involved in the care of patients with genital herpes. The information provided would help to improve the counseling of affected patients and to optimize the diagnosis, treatment, and prevention of this particular disease.

  4. No. 207-Genital Herpes: Gynaecological Aspects.

    Science.gov (United States)

    Money, Deborah; Steben, Marc

    2017-07-01

    The purpose of this guideline is to provide recommendations to gynaecology health care providers on optimal management of genital herpes. More effective prevention of complications and transmission of genital herpes. Medline was searched for articles published in French and English related to genital herpes and gynaecology. Additional articles were identified through the references of these articles. All study types and recommendation reports were reviewed. Copyright © 2017. Published by Elsevier Inc.

  5. Herpes simplex virus following stab phlebectomy.

    Science.gov (United States)

    Hicks, Caitlin W; Lum, Ying Wei; Heller, Jennifer A

    2017-03-01

    Herpes simplex virus infection following surgery is an unusual postoperative phenomenon. Many mechanisms have been suggested, with the most likely explanation related to latent virus reactivation due to a proinflammatory response in the setting of local trauma. Here, we present a case of herpes simplex virus reactivation in an immunocompetent female following a conventional right lower extremity stab phlebectomy. Salient clinical and physical examination findings are described, and management strategies for herpes simplex virus reactivation are outlined. This is the first known case report of herpes simplex virus reactivation following lower extremity phlebectomy.

  6. Polyneuritis cranialis following herpes zoster

    Directory of Open Access Journals (Sweden)

    Radhakrishna H

    2000-01-01

    Full Text Available Herpes zoster is a common clinical condition involving cranial nerves. We encountered 3 cases in which multiple cranial nerves were involved besides the commoner ones. All the three cases were treated with acyclovir and oral steroids. Recovery of motor function was only partial in all three cases when reviewed 2 months after discharge. The clinical details and a brief review of literature are presented.

  7. Genetic Recombination

    Science.gov (United States)

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  8. Interaction of infectious spleen and kidney necrosis virus ORF119L with PINCH leads to dominant-negative inhibition of integrin-linked kinase and cardiovascular defects in zebrafish.

    Science.gov (United States)

    Yuan, Ji-Min; He, Bai-Liang; Yang, Lu-Yun; Guo, Chang-Jun; Weng, Shao-Ping; Li, Shengwen Calvin; He, Jian-Guo

    2015-01-01

    Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus, Iridoviridae family, causing a severe systemic disease with high mortality in mandarin fish (Siniperca chuatsi) in China and Southeast Asia. At present, the pathogenesis of ISKNV infection is still not fully understood. Based on a genome-wide bioinformatics analysis of ISKNV-encoded proteins, we found that ISKNV open reading frame 119L (ORF119L) is predicted to encode a three-ankyrin-repeat (3ANK)-domain-containing protein, which shows high similarity to the dominant negative form of integrin-linked kinase (ILK); i.e., viral ORF119L lacks the ILK kinase domain. Thus, we speculated that viral ORF119L might affect the host ILK complex. Here, we demonstrated that viral ORF119L directly interacts with particularly interesting Cys-His-rich protein (PINCH) and affects the host ILK-PINCH interaction in vitro in fathead minnow (FHM) cells. In vivo ORF119L overexpression in zebrafish (Danio rerio) embryos resulted in myocardial dysfunctions with disintegration of the sarcomeric Z disk. Importantly, ORF119L overexpression in zebrafish highly resembles the phenotype of endogenous ILK inhibition, either by overexpressing a dominant negative form of ILK or by injecting an ILK antisense morpholino oligonucleotide. Intriguingly, ISKNV-infected mandarin fish develop disorganized sarcomeric Z disks in cardiomyocytes. Furthermore, phosphorylation of AKT, a downstream effector of ILK, was remarkably decreased in ORF119L-overexpressing zebrafish embryos. With these results, we show that ISKNV ORF119L acts as a domain-negative inhibitor of the host ILK, providing a novel mechanism for the megalocytivirus pathogenesis. Our work is the first to show the role of a dominant negative inhibitor of the host ILK from ISKNV (an iridovirus). Mechanistically, the viral ORF119L directly binds to the host PINCH, attenuates the host PINCH-ILK interaction, and thus impairs ILK signaling. Intriguingly

  9. Psychosocial Treatment for Recurrent Genital Herpes.

    Science.gov (United States)

    Longo, David J.; And Others

    1988-01-01

    Assigned 21 individuals with recurrent genital herpes to psychosocial intervention, social support, or waiting-list control conditions. Those receiving psychosocial intervention (herpes simplex virus information, relaxation training, stress management instructions, and an imagery technique) reported significantly greater reductions in herpes…

  10. Experiential Interventions for Clients with Genital Herpes.

    Science.gov (United States)

    Cummings, Anne L.

    1999-01-01

    Explores potential benefits of incorporating concepts and interventions from experimental therapy to help clients with psychosocial difficulties in learning to live with genital herpes. Recommends experimental counseling of two-chair dialog, empty chair, and metaphor for helping clients with emotional sequelae of genital herpes. Presents case…

  11. Recurrent facial urticaria following herpes simplex labialis

    Directory of Open Access Journals (Sweden)

    Vijay Zawar

    2012-01-01

    Full Text Available We describe recurrent acute right-sided facial urticaria associated with herpes labialis infection in a middle-aged female patient. Antiviral medications and antihistamines not only successfully cleared the herpes infection and urticaria but also prevented further recurrences.

  12. Neonatal herpes in Denmark 1977-1991

    DEFF Research Database (Denmark)

    Fonnest, G; de la Fuente Fonnest, I; Weber, Tom

    1997-01-01

    BACKGROUND: To prevent neonatal herpes, women in labor with genital herpes infection are still delivered by Cesarean section. This policy is currently being debated. The aim of this study was to determine the incidence of neonatal herpes in Denmark and to evaluate the prevention practice. METHODS......: All newborns with perinatal herpes in Denmark 1977-1991 were identified from hospital-records. RESULTS: Of 862,298 deliveries 136 possible cases were found but only 30 (22%) fulfilled the criteria for neonatal herpes. The incidence increased from 2.36 to 4.56 per 100,000 live births during 1977......%) did not have any sequelae. Four (13%) died. Six (20%) had serious neurological sequelae. Seven (23%) only had cutaneous recurrences. In seven cases (23%) information was insufficient. CONCLUSIONS: During a 15 year period in Denmark only one neonate had serious sequelae following a recognized maternal...

  13. Neonatal Herpes Simplex Virus Infection.

    Science.gov (United States)

    James, Scott H; Kimberlin, David W

    2015-09-01

    Herpes simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Primary Genital Herpes Diseases in İnfancy

    Directory of Open Access Journals (Sweden)

    Sevinç Gümüş Pekacar

    2016-09-01

    Full Text Available Symptomatic primary genital herpes infection is very rare in early childhood. Herpes simplex virus 1 type is the infectious agent in 20-50% percent of primery infections. Sexual abuse should be considered when genital herpes is seen in a person before sexual active age. It is mild and self limiting unless the patient is immune compramised. In this paper we discussed a 17 months old patient with genital herpes and approach to genital herpes in children.

  15. Retargeting Strategies for Oncolytic Herpes Simplex Viruses.

    Science.gov (United States)

    Campadelli-Fiume, Gabriella; Petrovic, Biljana; Leoni, Valerio; Gianni, Tatiana; Avitabile, Elisa; Casiraghi, Costanza; Gatta, Valentina

    2016-02-26

    Most of the oncolytic herpes simplex viruses (HSVs) exhibit a high safety profile achieved through attenuation. They carry defects in virulence proteins that antagonize host cell response to the virus, including innate response, apoptosis, authophagy, and depend on tumor cell proliferation. They grow robustly in cancer cells, provided that these are deficient in host cell responses, which is often the case. To overcome the attenuation limits, a strategy is to render the virus highly cancer-specific, e.g., by retargeting their tropism to cancer-specific receptors, and detargeting from natural receptors. The target we selected is HER-2, overexpressed in breast, ovarian and other cancers. Entry of wt-HSV requires the essential glycoproteins gD, gH/gL and gB. Here, we reviewed that oncolytic HSV retargeting was achieved through modifications in gD: the addition of a single-chain antibody (scFv) to HER-2 coupled with appropriate deletions to remove part of the natural receptors' binding sites. Recently, we showed that also gH/gL can be a retargeting tool. The insertion of an scFv to HER-2 at the gH N-terminus, coupled with deletions in gD, led to a recombinant capable to use HER-2 as the sole receptor. The retargeted oncolytic HSVs can be administered systemically by means of carrier cells-forcedly-infected mesenchymal stem cells. Altogether, the retargeted oncolytic HSVs are highly cancer-specific and their replication is not dependent on intrinsic defects of the tumor cells. They might be further modified to express immunomodulatory molecules.

  16. Replication-Competent Controlled Herpes Simplex Virus.

    Science.gov (United States)

    Bloom, David C; Feller, Joyce; McAnany, Peterjon; Vilaboa, Nuria; Voellmy, Richard

    2015-10-01

    We present the development and characterization of a replication-competent controlled herpes simplex virus 1 (HSV-1). Replication-essential ICP4 and ICP8 genes of HSV-1 wild-type strain 17syn+ were brought under the control of a dually responsive gene switch. The gene switch comprises (i) a transactivator that is activated by a narrow class of antiprogestins, including mifepristone and ulipristal, and whose expression is mediated by a promoter cassette that comprises an HSP70B promoter and a transactivator-responsive promoter and (ii) transactivator-responsive promoters that drive the ICP4 and ICP8 genes. Single-step growth experiments in different cell lines demonstrated that replication of the recombinant virus, HSV-GS3, is strictly dependent on an activating treatment consisting of administration of a supraphysiological heat dose in the presence of an antiprogestin. The replication-competent controlled virus replicates with an efficiency approaching that of the wild-type virus from which it was derived. Essentially no replication occurs in the absence of activating treatment or if HSV-GS3-infected cells are exposed only to heat or antiprogestin. These findings were corroborated by measurements of amounts of viral DNA and transcripts of the regulated ICP4 gene and the glycoprotein C (gC) late gene, which was not regulated. Similar findings were made in experiments with a mouse footpad infection model. The alphaherpesviruses have long been considered vectors for recombinant vaccines and oncolytic therapies. The traditional approach uses vector backbones containing attenuating mutations that restrict replication to ensure safety. The shortcoming of this approach is that the attenuating mutations tend to limit both the immune presentation and oncolytic properties of these vectors. HSV-GS3 represents a novel type of vector that, when activated, replicates with the efficiency of a nonattenuated virus and whose safety is derived from deliberate, stringent regulation of

  17. The genital herpes problem in pregnancy.

    Science.gov (United States)

    Guerra, B; Puccetti, C; Cervi, F

    2012-10-01

    Genital herpes is a common sexually transmitted infection. In reproductive age it involves the additional risk of vertical transmission to the neonate. Rates of transmission are affected by the viral type and whether the infection around delivery is primary or recurrent. Neonatal herpes is a rare but very severe complication of genital herpes infection and is caused by contact with infected genital secretions at the time of labor. Maternal acquisition of herpes simplex virus (HSV) in the third trimester of pregnancy carries the highest risk of neonatal transmission. Prevention of neonatal herpes depends on preventing acquisition of genital HSV infection during late pregnancy and avoiding exposure of the infant to herpetic lesions during delivery. Uninfected woman should be counselled about the need of avoiding sexual contact during the third trimester. Elective caesarean section before the onset of labor is the choice mode of delivery for women with genital lesions or with prodromal symptoms near the term, even if it offers only a partial protection against neonatal infection. Antiviral suppressive therapy is used from 36 weeks of gestation until delivery in pregnant women with recurrences to prevent genital lesions at the time of labor so reducing the need of caesarean sections. Currently, routine maternal serologic screening is not yet recommended. Because most mothers of infants who acquire neonatal herpes lack histories of clinically evident genital herpes, researchers should focus on the recognition of asymptomatic primary genital HSV infections.

  18. Phylogenetic and recombination analysis of the herpesvirus genus varicellovirus.

    Science.gov (United States)

    Kolb, Aaron W; Lewin, Andrew C; Moeller Trane, Ralph; McLellan, Gillian J; Brandt, Curtis R

    2017-11-21

    The varicelloviruses comprise a genus within the alphaherpesvirus subfamily, and infect both humans and other mammals. Recently, next-generation sequencing has been used to generate genomic sequences of several members of the Varicellovirus genus. Here, currently available varicellovirus genomic sequences were used for phylogenetic, recombination, and genetic distance analysis. A phylogenetic network including genomic sequences of individual species, was generated and suggested a potential restriction between the ungulate and non-ungulate viruses. Intraspecies genetic distances were higher in the ungulate viruses (pseudorabies virus (SuHV-1) 1.65%, bovine herpes virus type 1 (BHV-1) 0.81%, equine herpes virus type 1 (EHV-1) 0.79%, equine herpes virus type 4 (EHV-4) 0.16%) than non-ungulate viruses (feline herpes virus type 1 (FHV-1) 0.0089%, canine herpes virus type 1 (CHV-1) 0.005%, varicella-zoster virus (VZV) 0.136%). The G + C content of the ungulate viruses was also higher (SuHV-1 73.6%, BHV-1 72.6%, EHV-1 56.6%, EHV-4 50.5%) compared to the non-ungulate viruses (FHV-1 45.8%, CHV-1 31.6%, VZV 45.8%), which suggests a possible link between G + C content and intraspecies genetic diversity. Varicellovirus clade nomenclature is variable across different species, and we propose a standardization based on genomic genetic distance. A recent study reported no recombination between sequenced FHV-1 strains, however in the present study, both splitstree, bootscan, and PHI analysis indicated recombination. We also found that the recently sequenced Brazilian CHV-1 strain BTU-1 may contain a genetic signal in the UL50 gene from an unknown varicellovirus. Together, the data contribute to a greater understanding of varicellovirus genomics, and we also suggest a new clade nomenclature scheme based on genetic distances.

  19. The direct effect of Focal Adhesion Kinase (FAK, dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2009-08-01

    Full Text Available Abstract Background Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis. Methods To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD, and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation in vitro, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD in vivo, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors. Results Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability in vitro and inhibited tumorigenesis in vivo. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p Conclusion Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis in vivo and reveal

  20. Generating protective immunity against genital herpes.

    Science.gov (United States)

    Shin, Haina; Iwasaki, Akiko

    2013-10-01

    Genital herpes is an incurable, chronic disease that affects millions of people worldwide. Not only does genital herpes cause painful, recurrent symptoms, it is also a significant risk factor for the acquisition of other sexually transmitted infections such as HIV-1. Antiviral drugs are used to treat herpes simplex virus (HSV) infection, but they cannot stop viral shedding and transmission. Thus, developing a vaccine that can prevent or clear infection will be crucial in limiting the spread of disease. In this review we outline recent studies that improve our understanding of host responses against HSV infection, discuss past clinical vaccine trials, and highlight new strategies for vaccine design against genital herpes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Herpes Simplex Virus-1 and Bell's Palsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-05-01

    Full Text Available The association between herpes simplex virus-1 (HSV-1 infection and Bell palsy was determined in 47 children studied at Children's Hospital at Montefiore, Bronx, NY. Swabs of saliva and conjunctiva were taken for PCR testing.

  2. Herpes zoster - typical and atypical presentations.

    Science.gov (United States)

    Dayan, Roy Rafael; Peleg, Roni

    2017-08-01

    Varicella- zoster virus infection is an intriguing medical entity that involves many medical specialties including infectious diseases, immunology, dermatology, and neurology. It can affect patients from early childhood to old age. Its treatment requires expertise in pain management and psychological support. While varicella is caused by acute viremia, herpes zoster occurs after the dormant viral infection, involving the cranial nerve or sensory root ganglia, is re-activated and spreads orthodromically from the ganglion, via the sensory nerve root, to the innervated target tissue (skin, cornea, auditory canal, etc.). Typically, a single dermatome is involved, although two or three adjacent dermatomes may be affected. The lesions usually do not cross the midline. Herpes zoster can also present with unique or atypical clinical manifestations, such as glioma, zoster sine herpete and bilateral herpes zoster, which can be a challenging diagnosis even for experienced physicians. We discuss the epidemiology, pathophysiology, diagnosis and management of Herpes Zoster, typical and atypical presentations.

  3. Herpes Genitalis: Diagnosis, Treatment and Prevention

    Science.gov (United States)

    Sauerbrei, A.

    2016-01-01

    Herpes genitalis is caused by the herpes simplex virus type 1 or type 2 and can manifest as primary or recurrent infection. It is one of the most common sexually transmitted infections and due to associated physical and psychological morbidity it constitutes a considerable, often underestimated medical problem. In addition to providing the reader with basic knowledge of the pathogen and clinical presentation of herpes genitalis, this review article discusses important aspects of the laboratory diagnostics, antiviral therapy and prophylaxis. The article is aimed at all health-care workers managing patients with herpes genitalis and attempts to improve the often suboptimal counselling, targeted use of laboratory diagnostics, treatment and preventive measures provided to patients. PMID:28017972

  4. Atypical Genital Herpes: Report of Five Cases

    OpenAIRE

    UUSKÜLA, ANNELI; RAUKAS, ELVE

    2004-01-01

    Manifestations of human genital herpes virus (HSV) infection are not limited to the typical cluster of genital lesions. Here we present 5 case histories suggestive to clinically atypical genital herpes (HSV detected with the polymerase chain reaction) collected in 2001 from a private outpatient clinic specializing in dermatological and venereal diseases. The clinical presentations included mucopurulent cervicitis, haemorrhagic cystitis, recurrent urethritis, and lower hack pain.

  5. Atypical genital herpes: report of five cases.

    Science.gov (United States)

    Uusküla, Anneli; Raukas, Elve

    2004-01-01

    Manifestations of human genital herpes virus (HSV) infection are not limited to the typical cluster of genital lesions. Here we present 5 case histories suggestive to clinically atypical genital herpes (HSV detected with the polymerase chain reaction) collected in 2001 from a private outpatient clinic specializing in dermatological and venereal diseases. The clinical presentations included mucopurulent cervicitis, haemorrhagic cystitis, recurrent urethritis, and lower back pain.

  6. Herpes Simplex Virus Infection in Pregnancy

    Directory of Open Access Journals (Sweden)

    Gianluca Straface

    2012-01-01

    The greatest risk of transmission to the fetus and the newborn occurs in case of an initial maternal infection contracted in the second half of pregnancy. The risk of transmission of maternal-fetal-neonatal herpes simplex can be decreased by performing a treatment with antiviral drugs or resorting to a caesarean section in some specific cases. The purpose of this paper is to provide recommendations on management of herpes simplex infections in pregnancy and strategies to prevent transmission from mother to fetus.

  7. C-terminal region of herpes simplex virus ICP8 protein needed for intranuclear localization

    International Nuclear Information System (INIS)

    Taylor, Travis J; Knipe, David M.

    2003-01-01

    The herpes simplex virus single-stranded DNA-binding protein, ICP8, localizes initially to structures in the nucleus called prereplicative sites. As replication proceeds, these sites mature into large globular structures called replication compartments. The details of what signals or proteins are involved in the redistribution of viral and cellular proteins within the nucleus between prereplicative sites and replication compartments are poorly understood; however, we showed previously that the dominant-negative d105 ICP8 does not localize to prereplicative sites and prevents the localization of other viral proteins to prereplicative sites (J. Virol. 74 (2000) 10122). Within the residues deleted in d105 (1083 to 1168), we identified a region between amino acid residues 1080 and 1135 that was predicted by computer models to contain two α-helices, one with considerable amphipathic nature. We used site-specific and random mutagenesis techniques to identify residues or structures within this region that are required for proper ICP8 localization within the nucleus. Proline substitutions in the predicted helix generated ICP8 molecules that did not localize to prereplicative sites and acted as dominant-negative inhibitors. Other substitutions that altered the charged residues in the predicted α-helix to alanine or leucine residues had little or no effect on ICP8 intranuclear localization. The predicted α-helix was dispensable for the interaction of ICP8 with the U L 9 origin-binding protein. We propose that this C-terminal α-helix is required for localization of ICP8 to prereplicative sites by binding viral or cellular factors that target or retain ICP8 at specific intranuclear sites

  8. Genital Herpes in Marital Partners

    Directory of Open Access Journals (Sweden)

    Mary Jacob

    1988-01-01

    Full Text Available During 1983-86, 225 patients were clinically diagnosed to have genital herpes (GH at our clinic. Of these, 90 men and 55 women were currently married. All the spouses were screened clinically and through standardized techniques for isolation and typing of herpes simplex virus, serological testing and Papanicolaou smear. There were 90 couples in whom at least one spouse had GH and in 38 (42% couples both partners had GH. Clinically, 49% of wives and 75% of husbands of GH patients were diagnosed to have the disease. The spouses of recurrent GH patients had a higher frequency of the disease than spouses of primary GH patients. Among spouses who were clinically asymptomatic, 40% had high serological titres suggestive of GH. Wives generally experienced more severe symptoms, especially pain in the lesions. Majority of lesions in both the partners were vesicles and ulcers. Prodromata were more among recurrent GH patients in both the partners. The frequency of recurrences wasalso similar in spouses. Seventy percent of wives and 40% of husbands could not identify any precipitating factor. Intercourse, physical stress and rich food were cited as possible factors in the remaining. All the wives had acquired the diseases through their husbands who were promiscuous. Fifty percent of husbands had been infected before marriage. Given the fact that asymptomatic carriers exist, it is better to consider all marital partners of GH as infected. Repeated and long-term follow, - up examination, particularly of wives of GH patients is therefore essential as an important socio-preventive aspect of this disease.

  9. Herpes

    Science.gov (United States)

    ... Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle Antibody (SMA) ... turn around. Specialty Laboratories [On-line test information]. PDF available for download at http://www.specialtylabs.com/ ...

  10. Herpes simplex-virus type 1 påvist hos patient med herpes zoster

    DEFF Research Database (Denmark)

    Danielsen, Patricia Louise; Schønning, Kristian; Larsen, Helle Kiellberg

    2012-01-01

    In this case report we present an otherwise healthy 63 year-old male patient with herpes zoster corresponding to the 2nd left branch of the trigeminal nerve. Real time-polymerase chain reaction analyses were positive for both herpes simplex virus (HSV) type 1 and varicella zoster virus (VZV......). The most probable explanation is that this reflects asymptomatic, latent expression of HSV-1 in a herpes zoster patient with no clinical relevance. Another hypothesis is that reactivation of a neurotropic herpes virus can reactivate another neurotropic virus if both types are present in the same ganglion....... If co-infection with HSV/VZV is suspected the treatment regimen for herpes zoster will sufficiently treat a possible HSV infection also....

  11. Expression of IFN-Inducible Genes with Antiviral Function OAS1 and MX1 in Health and under Conditions of Recurrent Herpes Simplex Infection.

    Science.gov (United States)

    Karaulov, A V; Shulzhenko, A E; Karsonova, A V

    2017-07-01

    We studied the expression of IFN-inducible genes OAS1 and Mx1 in lysates of peripheral blood mononuclear cells from patients suffering from recurrent Herpes simplex infections in comparison with healthy people. To induce the expression of the studied genes, blood mononuclears were incubated with recombinant IFN-α2b in concentrations of 1, 10, and 100 U/ml for 3 h and then the content of the studied transcripts was evaluated. Relative expression of OAS1 and Mx1 in patients with recurrent forms of Herpes simplex both during the acute stage and clinical remission did not differ significantly from that in healthy people after stimulation with IFN-α2b in a concentration of 1 U/ml and in higher concentrations (10 and 100 U/ml). It was concluded that intracellular signal transduction in IFN-α-activated cells in vitro was not disturbed in patients with recurrent forms of Herpes simplex infection. Thus, the reported phenomenon of IFN-signalling distortion by Herpes simplex virus proteins observed in experiments on model cell lines infected with Herpes simplex virus was not confirmed in our experiments on peripheral blood mononuclear cells from patients with Herpes simplex infection.

  12. The inner ear contains heteromeric channels composed of cx26 and cx30 and deafness-related mutations in cx26 have a dominant negative effect on cx30.

    Science.gov (United States)

    Forge, Andrew; Marziano, Nerissa K; Casalotti, Stefano O; Becker, David L; Jagger, Daniel

    2003-01-01

    Cx26 and cx30 co-localize in tissues of the mammalian cochlea. Transfected HeLa cells were used to examine interactions between cx26 and cx30 and the effects on cx30 of four point mutations in cx26 that are associated with dominantly inherited hearing loss--W44S, G59A, D66H and R75W. When co-expressed, wtcx26 and wtcx30 trafficked to the same gap junction plaques. Cells transferred neurobiotin but not Lucifer Yellow, which passes freely through cx26 channels, suggesting cx30 affects the properties of cx26. G59A and D66H had a perinuclear localization when expressed alone but trafficked to the membrane when co-expressed with cx30. Co-expression of W44S, G59A or R75W with cx30, significantly reduced neurobiotin transfer in comparison with cells expressing cx30 only. These results indicate that cx26 and cx30 can oligomerize to form heteromeric connexons and demonstrate a dominant negative effect of some cx26 mutants on cx30. Immunogold labeling of thin sections of the cochlea showed both cx26 and cx30 distributed evenly on both sides of individual gap junction profiles. Immunoprecipitation of cochlear membrane proteins, isolated by procedures that preserve connexons, with either cx30 or cx26 antibodies precipitated both cx26 and cx30. Following co-injection of Lucifer Yellow and neurobiotin into individual supporting cells of the organ of Corti in cochlear slices, neurobiotin transferred to many cells, but Lucifer Yellow was retained in the injected cell. These observations are consistent with junctions composed of cx26/cx30 heteromeric connexons in the cochlea. The functional disruption caused by some cx26 mutations upon such heteromeric channels may underlie the non-syndromic nature of their effects on hearing.

  13. A naturally occurring C-terminal fragment of the prion protein (PrP) delays disease and acts as a dominant-negative inhibitor of PrPSc formation.

    Science.gov (United States)

    Westergard, Laura; Turnbaugh, Jessie A; Harris, David A

    2011-12-23

    The cellular prion protein (PrPC) undergoes constitutive proteolytic cleavage between residues 111/112 to yield a soluble N-terminal fragment (N1) and a membrane-anchored C-terminal fragment (C1). The C1 fragment represents the major proteolytic fragment of PrPC in brain and several cell types. To explore the role of C1 in prion disease, we generated Tg(C1) transgenic mice expressing this fragment (PrP(Δ23-111)) in the presence and absence of endogenous PrP. In contrast to several other N-terminally deleted forms of PrP, the C1 fragment does not cause a spontaneous neurological disease in the absence of endogenous PrP. Tg(C1) mice inoculated with scrapie prions remain healthy and do not accumulate protease-resistant PrP, demonstrating that C1 is not a substrate for conversion to PrPSc (the disease-associated isoform). Interestingly, Tg(C1) mice co-expressing C1 along with wild-type PrP (either endogenous or encoded by a second transgene) become ill after scrapie inoculation, but with a dramatically delayed time course compared with mice lacking C1. In addition, accumulation of PrPSc was markedly slowed in these animals. Similar effects were produced by a shorter C-terminal fragment of PrP(Δ23-134). These results demonstrate that C1 acts as dominant-negative inhibitor of PrPSc formation and accumulation of neurotoxic forms of PrP. Thus, C1, a naturally occurring fragment of PrPC, might play a modulatory role during the course of prion diseases. In addition, enhancing production of C1, or exogenously administering this fragment, represents a potential therapeutic strategy for the treatment of prion diseases.

  14. CBO-richtlijn 'Seksueel overdraagbare aandoeningen en herpes neonatorum' (herziening)

    NARCIS (Netherlands)

    Bleker, O. P.; van der Meijden, W. I.; Wittenberg, J.; van Bergen, J. E. A. M.; Boeke, A. J. P.; van Doornum, G. J. J.; Henquet, C. J. M.; Galama, J. M. D.; Postma, M. J.; Prins, J. M.; van Voorst Vader, P. C.

    2003-01-01

    The Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes' summarises the current scientific position on the diagnosis and treatment of a great number of sexually transmitted diseases (STD) and neonatal herpes. Symptomatic treatment of

  15. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Herpes simplex virus serological assays. 866.3305... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3305 Herpes simplex virus serological assays. (a) Identification. Herpes simplex virus serological assays are devices...

  16. Pathogenesis of herpes simplex virus infections of the cornea

    NARCIS (Netherlands)

    J. Maertzdorf (Jeroen)

    2002-01-01

    textabstractThe identification of human herpes virus (HHV) infections can be traced back to ancient Greece where Herpes simplex vims (HSV) infections in humans were first documented. Hippocrates used the word "herpes", meaning to creep or crawl, to describe spreading skin lesions. Although the

  17. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  18. Designing herpes viruses as oncolytics

    Science.gov (United States)

    Peters, Cole; Rabkin, Samuel D

    2015-01-01

    Oncolytic herpes simplex virus (oHSV) was one of the first genetically-engineered oncolytic viruses. Because HSV is a natural human pathogen that can cause serious disease, it is incumbent that it can be genetically-engineered or significantly attenuated for safety. Here, we present a detailed explanation of the functions of HSV-1 genes frequently mutated to endow oncolytic activity. These genes are nonessential for growth in tissue culture cells but are important for growth in postmitotic cells, interfering with intrinsic antiviral and innate immune responses or causing pathology, functions dispensable for replication in cancer cells. Understanding the function of these genes leads to informed creation of new oHSVs with better therapeutic efficacy. Virus infection and replication can also be directed to cancer cells through tumor-selective receptor binding and transcriptional- or post-transcriptional miRNA-targeting, respectively. In addition to the direct effects of oHSV on infected cancer cells and tumors, oHSV can be “armed” with transgenes that are: reporters, to track virus replication and spread; cytotoxic, to kill uninfected tumor cells; immune modulatory, to stimulate antitumor immunity; or tumor microenvironment altering, to enhance virus spread or to inhibit tumor growth. In addition to HSV-1, other alphaherpesviruses are also discussed for their oncolytic activity. PMID:26462293

  19. DIAGNOSIS DAN TATA LAKSANA ENSEFALITIS HERPES SIMPLEKS

    Directory of Open Access Journals (Sweden)

    Tri Yuliantini

    2014-12-01

    Full Text Available Infeksi Herpes simpleks pada susunan saraf pusat (SSP merupakan infeksi SSP yang paling beratdan sering berakibat fatal. Angka kejadiannya diperkirakan 1 kasus per 250 000 sampai 500 000orang per tahun, sepertiganya terjadi pada anak-anak. Gejala dan tanda klinis pada fase awal sangattidak khas. Pemberian terapi yang terlambat membawa dampak terjadinya kecacatan permanen.Deteksi virus Herpes simpleks (VHS di dalam cairan serebrospinal dengan polymerase chain reactionmerupakan modalitas pilihan untuk diagnosis ensefalitis herpes simpleks (EHS. Asiklovir intravenamerupakan obat pilihan pertama. Pengobatan segera diberikan kepada pasien yang dicurigai menderitaEHS, kemudian pengobatan dapat dilanjutkan atau dihentikan sesuai konfirmasi laboratorium atauhasil biopsi otak. Pasien yang tidak diberikan antivirus atau pengobatannya terlambat angkakematiannya cukup tinggi.

  20. [Immune evasion by herpes simplex viruses].

    Science.gov (United States)

    Retamal-Díaz, Angello R; Suazo, Paula A; Garrido, Ignacio; Kalergis, Alexis M; González, Pablo A

    2015-02-01

    Herpes simplex viruses and humans have co-existed for tens of thousands of years. This long relationship has translated into the evolution and selection of viral determinants to evade the host immune response and reciprocally the evolution and selection of host immune components for limiting virus infection and damage. Currently there are no vaccines available to avoid infection with these viruses or therapies to cure them. Herpes simplex viruses are neurotropic and reside latently in neurons at the trigeminal and dorsal root ganglia, occasionally reactivating. Most viral recurrences are subclinical and thus, unnoticed. Here, we discuss the initial steps of infection by herpes simplex viruses and the molecular mechanisms they have developed to evade innate and adaptive immunity. A better understanding of the molecular mechanisms evolved by these viruses to evade host immunity should help us envision novel vaccine strategies and therapies that limit infection and dissemination.

  1. Radionuclide imaging in herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Karlin, C.A.; Robinson, R.G.; Hinthorn, D.R.; Liu, C.

    1978-01-01

    Eight patients with herpes simplex encephalitis among the 10 cases diagnosed at the University of Kansas Medical Center from 1966 to 1976 were studied with /sup 99m/Tc early in their diagnostic work-up. The images were unilaterally positive in the temporal lobe area in all 8 patients. Radionuclide studies can suggest herpes simplex as the specific etiology in cases of encephalitis and can also indicate the best site for brain biopsy to confirm the diagnosis by fluorescent antibody techniques. Appropriate antiviral therapy should be instituted as soon as possible to alter the course of this destructive form of viral encephalitis

  2. SHORT COMMUNICATION Serological profiles of Herpes simplex ...

    African Journals Online (AJOL)

    Dr.Mirambo

    Journal of Infectious Diseases, 185, 45-52. Watson-Jones, D., Weiss, H.A., Rusizoka, M., Changalucha, J., Baisley, K., Mugeye, K., Tanton, C.,. Ross, D., Everett, D. & Clayton, T. (2008) Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. New England Journal of Medicine 358: 1560-1571.

  3. Antiviral drug resistance of herpes simplex virus

    NARCIS (Netherlands)

    Stranska, Ruzena

    2004-01-01

    Infections with herpes simplex virus (HSV) usually have an asymptomatic or benign course. However, severe infections do occur, particularly in HIV/AIDS patients or transplant recipients, and may be life-threatening unless adequate antiviral therapy is given. Since its introduction in the early

  4. Forebyggelse af herpes zoster med vaccination

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan

    2011-01-01

    Herpes zoster (HZ) and post-herpetic neuralgia (PHN) are frequently occurring diseases in elderly and in immuno-compromised persons. The live attenuated HZ vaccine boosts an existing immune response, so that the already established varicella-zoster virus infection is kept latent. Vaccination has...

  5. Herpes zoster: klinik, diagnostik og behandling

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan

    2011-01-01

    Herpes zoster (HZ) is a painful vesicular rash localized to one dermatome. Post-herpetic neuralgia (PHN) is persistent pain three months after the rash started. In recent years several Cochrane reviews and clinical studies on how to treat HZ and PHN have been published. These studies show...

  6. Can Herpes Simplex Virus Encephalitis Cause Aphasia?

    Science.gov (United States)

    Naude, H.; Pretorius, E.

    2003-01-01

    Aphasia implies the loss or impairment of language caused by brain damage. The key to understanding the nature of aphasic symptoms is the neuro-anatomical site of brain damage, and not the causative agent. However, because "Herpes simplex" virus (HSV) encephalitis infection usually affects the frontal and temporal lobes, subcortical…

  7. Recurrent Herpes Zoster- A Marker of AIDS

    Directory of Open Access Journals (Sweden)

    Mazumdar Gautam

    2003-01-01

    Full Text Available A 32 year old female presented to us with herpes zoster involving the T 8 to T 10 dermatomes. She had a scar involving the same dermatomes on the other half of the body. Investigations revealed that both the patient and her husband were HIV positive with CD4 cell count less than 200.

  8. [Intrauterine herpes simplex virus infection].

    Science.gov (United States)

    Hoppen, T; Eis-Hübinger, A M; Schild, R L; Enders, G; Hansmann, M; Rister, M; Bartmann, P

    2001-01-01

    Early fetal herpes simplex virus (HSV) infection is rarely documented. Only the minority of affected fetuses survive this condition. At 19 weeks of gestation the first episode of a genital HSV-infection of a pregnant woman was treated with local interferon beta. At 34 weeks of gestation hydrocephalus with secondary microcephaly and microphthalmia of both eyes was detected by ultrasonography. In the amniotic fluid HSV type 2 (HSV-2) was isolated and HSV-2-DNA was detected by PCR. The serum of the mother proved positive for HSV-2 (glycoprotein G2)-specific IgG-antibodies. No other infectious causes were apparent on further testing. At 35 + 4 weeks gestation a small-for-gestational-age neonate (2130 g) with microcephaly (29 cm head circumference) was born by spontaneous vaginal delivery. Scarce ulcerative skin lesions and vesicles, hepatosplenomegaly and microphthalmia were diagnosed. Furthermore, encephalomalacia with parenchymal destruction, cataract of both eyes and aplasia of the maculae and papillae were found. HSV-2-PCR was tested positive in chorionic cells and an umbilical segment of the placenta as well as in swabs from both eyes, throat, and a herpetic skin lesion collected during the first 5 days of life. HSV-IgM-antibodies were found in the umbilical cord blood. Local and intravenous treatment with aciclovir was started. The infant exhibited signs of a severely malfunctioning central nervous system. At the age of 4 months the boy suffered from generalised cerebral seizures. He died at the age of 9 months as a consequence of respiratory insufficiency with consecutive circulation failure. The case of an intrauterine HSV-2-infection is presented. The time of onset of fetal infection was most probably at the time of the maternal disease (19 weeks of gestation). Inspite of the very early infection the fetus did not die in utero. Especially, if a primary genital HSV-2-infection of a pregnant woman is suspected, which can be proven by serological means only

  9. Epidemiology, treatment and prevention of herpes zoster: A comprehensive review.

    Science.gov (United States)

    Koshy, Elsam; Mengting, Lu; Kumar, Hanasha; Jianbo, Wu

    2018-01-01

    Herpes zoster is a major health burden that can affect individuals of any age. It is seen more commonly among individuals aged ≥50 years, those with immunocompromised status, and those on immunosuppressant drugs. It is caused by a reactivation of varicella zoster virus infection. Cell-mediated immunity plays a role in this reactivation. Fever, pain, and itch are common symptoms before the onset of rash. Post-herpetic neuralgia is the most common complication associated with herpes zoster. Risk factors and complications associated with herpes zoster depend on the age, immune status, and the time of initializing treatment. Routine vaccination for individuals over 60 years has shown considerable effect in terms of reducing the incidence of herpes zoster and post-herpetic neuralgia. Treatment with antiviral drugs and analgesics within 72 hours of rash onset has been shown to reduce severity and complications associated with herpes zoster and post-herpetic neuralgia. This study mainly focuses on herpes zoster using articles and reviews from PubMed, Embase, Cochrane library, and a manual search from Google Scholar. We cover the incidence of herpes zoster, gender distribution, seasonal and regional distribution of herpes zoster, incidence of herpes zoster among immunocompromised individuals, incidence of post-herpetic neuralgia following a zoster infection, complications, management, and prevention of herpes zoster and post-herpetic neuralgia.

  10. The potential of currently unavailable herpes virus vaccines.

    Science.gov (United States)

    Rajčáni, Július; Bánáti, Ferenc; Szenthe, Kálmán; Szathmary, Susan

    2018-03-01

    Despite overwhelming experimental work, there are no licensed vaccines against the most frequent Alphaherpesviruses, namely herpes simplex virus 1 and 2 (HSV1 and 2) nor against the Epstein-Barr virus (EBV), a member of the subfamily Gammaherpesvirus. Areas covered: Since the DNAs of both HSVs reside in the regional sensory ganglia in a latent state (i.e. as circularized episomal molecules), a corresponding vaccine might be useful for immunotherapy rather than for prevention of primary infection. Here we describe the design of a purified subunit vaccine as well as the preparation and efficacy of a recombinant fusion protein consisting of the gD ectodomain from our domestic attenuated HSV1 strain HSZP. The EBV vaccines considered so far, were destined for prevention of infectious mononucleosis (IM) or to prevent formation of EBV related tumors. To design the EBV peptide vaccine, at least 15 carefully selected immunogenic epitopes coming from 12 virus coded proteins were bound to synthetic micro-particle carriers along with a non-specific pathogen recognizing receptor (PRR) stimulating both the T as well as B lymphocytes. Expert commentary: The efficacy of a novel EBV peptide in the rabbit model was based on criteria such as antibody formation (EA-D detected by ELISA, early and capsid proteins tested by immunoblot), presence of LMP1 antigen and of viral DNA in peripheral white blood cells. Out of 19 peptide combinations used for vaccination, at least 6 showed a satisfactory protective effect.

  11. Evolution and Diversity in Human Herpes Simplex Virus Genomes

    Science.gov (United States)

    Gatherer, Derek; Ochoa, Alejandro; Greenbaum, Benjamin; Dolan, Aidan; Bowden, Rory J.; Enquist, Lynn W.; Legendre, Matthieu; Davison, Andrew J.

    2014-01-01

    Herpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a gene deletion and one-third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms, although the protein sequence identity between strains exceeds 90% on average. In the first genome-scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments and will aid in the selection of vaccine antigens that are invariant worldwide. PMID:24227835

  12. Herpes zoster duplex bilateralis in an immunocompetent host

    Directory of Open Access Journals (Sweden)

    Pratik Gahalaut

    2012-01-01

    Full Text Available Varicella zoster virus causes both chicken pox and herpes zoster. The phenomenon of herpes zoster occurring concurrently in two non-contiguous dermatomes involving different halves of the body is termed herpes zoster duplex bilateralis (HZDB. Few cases, reported in the literature, were seen in either an immunosuppressed host or in the older age group. Here we present a case of HZDB in an immunocompetent host, probably the first in India.

  13. 2014 UK national guideline for the management of anogenital herpes.

    Science.gov (United States)

    Patel, Raj; Green, John; Clarke, Emily; Seneviratne, Kanchana; Abbt, Naomi; Evans, Ceri; Bickford, Jane; Nicholson, Marian; O'Farrell, Nigel; Barton, Simon; FitzGerald, Mark; Foley, Elizabeth

    2015-10-01

    These guidelines concern the management of anogenital herpes simplex virus infections in adults and give advice on diagnosis, management, and counselling of patients. This guideline replaces the 2007 BASHH herpes guidelines and includes new sections on herpes proctitis, key points to cover with patients regarding transmission and removal of advice on the management of HSV in pregnancy which now has a separate joint BASHH/RCOG guideline. © The Author(s) 2015.

  14. Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

    Directory of Open Access Journals (Sweden)

    Aziz Alami Chentoufi

    2012-01-01

    Full Text Available Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2 are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed.

  15. Improving immunogenicity and efficacy of vaccines for genital herpes containing herpes simplex virus glycoprotein D.

    Science.gov (United States)

    Awasthi, Sita; Shaw, Carolyn; Friedman, Harvey

    2014-12-01

    No vaccines are approved for prevention or treatment of genital herpes. The focus of genital herpes vaccine trials has been on prevention using herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) alone or combined with glycoprotein B. These prevention trials did not achieve their primary end points. However, subset analyses reported some positive outcomes in each study. The most recent trial was the Herpevac Trial for Women that used gD2 with monophosphoryl lipid A and alum as adjuvants in herpes simplex virus type 1 (HSV-1) and HSV-2 seronegative women. Unexpectedly, the vaccine prevented genital disease by HSV-1 but not HSV-2. Currently, HSV-1 causes more first episodes of genital herpes than HSV-2, highlighting the importance of protecting against HSV-1. The scientific community is conflicted between abandoning vaccine efforts that include gD2 and building upon the partial successes of previous trials. We favor building upon success and present approaches to improve outcomes of gD2-based subunit antigen vaccines.

  16. Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

    Science.gov (United States)

    Chentoufi, Aziz Alami; BenMohamed, Lbachir

    2012-01-01

    Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed. PMID:23320014

  17. The Changing Epidemiology of Herpes Simplex Virus Type 1 Infection: The Associated Effects on the Incidence of Ocular Herpes

    Directory of Open Access Journals (Sweden)

    Abedi Kiasari, B.

    2016-07-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 with a worldwide distribution has been reported in all human populations, resulting in a clinical spectrum of infections. Although HSV type 2 (HSV-2 is known as the most common cause of genital herpes, an increasing number of cases with genital herpes are caused by HSV-1. The present study aimed to discuss the changes in the epidemiology of HSV-1 infection including the decline in the general incidence of HSV-1 infection in childhood and the increased rate of genital herpes, caused by HSV-1. Moreover, changes in the epidemiology of ocular herpes, i.e., the reduced rate of primary ocular herpes in children and increased incidence of ocular HSV infection in adults, were discussed.

  18. A case of Herpes encephalitis followed-up by CT

    International Nuclear Information System (INIS)

    Fukui, Yukiko; Nagai, Shinya; Nishibayashi, Yohei; Okamoto, Hirofumi; Goishi, Junji

    1982-01-01

    A 9-month-old girl was admitted with lethargy, fever and convulsion. EGG showed localized slow waves in the right temporal region. CT showed a localized low density area accompanied by a hemorrhagic focus in the right frontal lobe. Herpes encephalitis was suspected, and cytosine arabinoside was administered. The antibody titers of the serum and cerebrospinal fluid against herpes simplex virus type I significantly rose. Clinically the patient recovered without serious sequelae. CT revealed marked cerebral atrophy and subdural hematoma which were surgically treated. The importance of CT in the diagnosis and prognosis of herpes encephalitis was argued, and CT findings of herpes encephalitis were discussed. (Chiba, N.)

  19. Inactivation of Herpes Simplex Viruses by Nonionic Surfactants

    Science.gov (United States)

    Asculai, Samuel S.; Weis, Margaret T.; Rancourt, Martha W.; Kupferberg, A. B.

    1978-01-01

    Nonionic surface-active agents possessing ether or amide linkages between the hydrophillic and hydrophobic portions of the molecule rapidly inactivated the infectivity of herpes simplex viruses. The activity stemmed from the ability of nonionic surfactants to dissolve lipid-containing membranes. This was confirmed by observing surfactant destruction of mammalian cell plasma membranes and herpes simplex virus envelopes. Proprietary vaginal contraceptive formulations containing nonionic surfactants also inactivated herpes simplex virus infectivity. This observation suggests that nonionic surfactants in appropriate formulation could effectively prevent herpes simplex virus transmission. Images PMID:208460

  20. Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

    OpenAIRE

    Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

    2007-01-01

    Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generate...

  1. Decompressive craniectomy in herpes simplex encephalitis

    Directory of Open Access Journals (Sweden)

    Muhammed Jasim Abdul Jalal

    2015-01-01

    Full Text Available Intracranial hypertension is a common cause of morbidity in herpes simplex encephalitis (HSE. HSE is the most common form of acute viral encephalitis. Hereby we report a case of HSE in which decompressive craniectomy was performed to treat refractory intracranial hypertension. A 32-year-old male presented with headache, vomiting, fever, and focal seizures involving the right upper limb. Cerebrospinal fluid-meningoencephalitic profile was positive for herpes simplex. Magnetic resonance image of the brain showed swollen and edematous right temporal lobe with increased signal in gray matter and subcortical white matter with loss of gray, white differentiation in T2-weighted sequences. Decompressive craniectomy was performed in view of refractory intracranial hypertension. Decompressive surgery for HSE with refractory hypertension can positively affect patient survival, with good outcomes in terms of cognitive functions.

  2. [Ocular hypertension in herpes simplex keratouveitis].

    Science.gov (United States)

    Burcea, M; Avram, Corina-Ioana; Stamate, Alina-Cristina; Malciolu, R; Oprea, S; Zemba, M

    2014-01-01

    The herpes simplex virus is one of the most common pathogens in humans, who are seropositive for the virus in 90% of the cases at the adult age. It determines reccurent infections in more than a third of the population and these infections depend on the immune response of the host. Ocular infections of newborns are due to the herpes simplex virus type 2, meanwhile type 1 is found predominantly at adults; almost all ocular structures can be affected. HSV-1 in the most frequent etiologic agent in infectious anterior uveitis (with the varicelo-zosterian virus) and it is responsible for 6-10% of all cases of anterior uveitis. More than half of the keratouveitides due to HSV will develop intraocular hypertension and open-angle secondary glaucoma, during reccurences and most of them will resolve after proper control of inflammation.

  3. Ramsay hunt syndrome (herpes zoster oticus

    Directory of Open Access Journals (Sweden)

    S Karthiga Kannan

    2012-01-01

    Full Text Available Ramsay Hunt syndrome (RHS is defined as an acute peripheral facial neuropathy caused by the reactivated latent varicella zoster virus (VZV in the geniculate ganglion; characterized with erythematous vesicular rash of the skin of the ear canal, auricle, facial skin, oral mucosa and facial palsy (also known as herpes zoster oticus. This article reports a case of Ramsay Hunt Syndrome (RHS in a 37-year-old male patient depicting the classical signs.

  4. Serial CT scannings in herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Fukushima, Masashi; Sawada, Tohru; Kuriyama, Yoshihiro; Kinugawa, Hidekazu; Yamaguchi, Takenori

    1981-01-01

    Two patients with serologically confirmed herpes simplex encephalitis were studied by serial CT scannings. Case 1, a 60-year-old woman, was admitted to National Cardiovascular Center because of headache, fever, and attacks of Jacksonian seizure. Case 2, a 54-year-old man, was admitted because of fever, consciousness disturbance and right hemipare sis. Pleocytosis (mainly lymphocytes) and elevation of protein content in cerebrospinal fluid were observed in both cases. Both patients presented ''das apallische Syndrom'' one month after admission. The diagnosis of herpes simplex encephalitis was confirmed by typical clinical courses and by greater than fourfold rises in serum antibody titer for herpes simplex virus as well as that in cerebrospinal fluid in case 1. Characteristic CT findings observed in these two cases were summarized as follows: Within a week after the onset, no obvious abnormalities could be detected on CT scans (Case 1). Two weeks after the onset, a large low-density area appeared in the left temporal lobe and in the contralateral insular cortex with midline shift toward the right side (Case 2). One month later, an ill-defined linear and ring-like high-density area (Case 1), or a well-defined high-density area (Case 2), that was enhanced after contrast administration, was observed in the large low-density area in the temporal lobe. These findings were considered as characteristic for hemorrhagic encephalitis. These high-density areas disappeared two months later, however, widespread and intensified low-density areas still remained. In both cases, the basal ganglia and thalamus were completely spared on CT scans. From these observations, it can be concluded that serial CT scannings are quite useful for diagnosis of herpes simplex encephalitis. (author)

  5. Computed tomography of herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Rodiek, S.O.; Backmund, H.; Max-Planck-Institut fuer Psychiatrie, Muenchen

    1984-01-01

    Referring to 9 patients of our own material we report on the pattern of distribution and the development of CT-changes in herpes simplex encephalitis (HSE). Our cases include the outstanding findings of a primarily hemorrhagic HSE and an extensive calcification at the residual stage on the borderline of widespread tissue necrosis on a baby. With respect to literature we receive a quite homogenous picture, reflecting the crucial characteristics of the disease as known from neuropathology. (orig.) [de

  6. [Herpes simplex virus infections in Algiers].

    Science.gov (United States)

    Meguenni, S; Djenaoui, T; Bendib, A; Bouhadjar, H; Lalliam, N; Allouache, A; Bouguermouh, A

    1989-01-01

    The purpose of this study was to determine the prevalence of herpes simplex virus antibodies among the population in Algiers. Anti-bodies to HSV1 are acquired rapidly between the ages of 1 and 6 years and 81.25% of the population is HSV1 seropositive by 15 years of age. Patients suffering from genital disorders possess HSV type 2 antibodies at a rate significantly higher (p less than 0.001) than in the control group.

  7. Intracerebral hematoma complicating herpes simplex encephalitis.

    Science.gov (United States)

    Rodríguez-Sainz, Aida; Escalza-Cortina, Inés; Guio-Carrión, Laura; Matute-Nieves, Alexandra; Gómez-Beldarrain, Marian; Carbayo-Lozano, Guillermo; Garcia-Monco, Juan Carlos

    2013-10-01

    To describe two patients who developed an intracranial hematoma as a complication of temporal lobe encephalitis due to herpes simplex type 1 virus, and to review the literature. The first patient, a 45-year-old woman developed a brain hematoma in the location of the encephalitic lesion on day 9 after the onset of herpes simplex encephalitis (HSE) that required surgical evacuation. The second patient, a 53-year-old woman was being treated for HSE; on day 8 after admission a temporal lobe hematoma with midline shift was disclosed due to persistent headache. Both patients survived but were left with sequelae. We conducted a PubMed/MEDLINE search from 1986 to April 2013 on this topic. We have found 20 additional cases reported in the literature and review their characteristics. Hemorrhage was present on admission in 35% of pooled patients, and consistently involved the area of encephalitis. Clinical presentation of intracranial hemorrhage overlapped the encephalitic symptoms in two-thirds of the patients. Half of patients underwent surgery. Overall, mortality rate was low (5.2%), and half of patients fully recovered. Intracranial bleeding, although infrequent, can complicate the evolution of herpes simplex encephalitis and should be borne in mind since its presence may require neurosurgery. Although its presentation may overlap the encephalitic features, the lack of improvement or the worsening of initial symptoms, particularly during the second week of admission, should lead to this suspicion and to perform a neuroimaging study. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Herpes zoster oticus: A rare clinical entity.

    Science.gov (United States)

    Gondivkar, Shailesh; Parikh, Viren; Parikh, Rima

    2010-04-01

    Herpes zoster oticus also known as Ramsay Hunt syndrome is a rare complication of herpes zoster in which reactivation of latent varicella zoster virus infection in the geniculate ganglion causes otalgia, auricular vesicles, and peripheral facial paralysis. Ramsay Hunt syndrome is rare in children and affects both sexes equally. Incidence and clinical severity increases when host immunity is compromised. Because these symptoms do not always present at the onset, this syndrome can be misdiagnosed. Although secondary to Bell's palsy in terms of the cause of acute atraumatic peripheral facial paralysis, Ramsay Hunt syndrome, with incidence ranged from 0.3 to 18%, has a worse prognosis. Herpes zoster oticus accounts for about 12% cases of facial palsy, which is usually unilateral and complete and full recovery occurs in only about 20% of untreated patients. The most advisable method to treat Ramsay Hunt syndrome is the combination therapy with acyclovir and prednisone but still not promising, and several prerequisites are required for better results. We present a case of 32-year-old man suffering from Ramsay Hunt syndrome with grade V facial palsy treated effectively with rehabilitation program, after the termination of the combination therapy of acyclovir and prednisone.

  9. Herpes zoster oticus: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Shailesh Gondivkar

    2010-01-01

    Full Text Available Herpes zoster oticus also known as Ramsay Hunt syndrome is a rare complication of herpes zoster in which reactivation of latent varicella zoster virus infection in the geniculate ganglion causes otalgia, auricular vesicles, and peripheral facial paralysis. Ramsay Hunt syndrome is rare in children and affects both sexes equally. Incidence and clinical severity increases when host immunity is compromised. Because these symptoms do not always present at the onset, this syndrome can be misdiagnosed. Although secondary to Bell′s palsy in terms of the cause of acute atraumatic peripheral facial paralysis, Ramsay Hunt syndrome, with incidence ranged from 0.3 to 18%, has a worse prognosis. Herpes zoster oticus accounts for about 12% cases of facial palsy, which is usually unilateral and complete and full recovery occurs in only about 20% of untreated patients. The most advisable method to treat Ramsay Hunt syndrome is the combination therapy with acyclovir and prednisone but still not promising, and several prerequisites are required for better results. We present a case of 32-year-old man suffering from Ramsay Hunt syndrome with grade V facial palsy treated effectively with rehabilitation program, after the termination of the combination therapy of acyclovir and prednisone.

  10. Herpes simplex virus type 1 is the leading cause of genital herpes in New Brunswick.

    Science.gov (United States)

    Garceau, Richard; Leblanc, Danielle; Thibault, Louise; Girouard, Gabriel; Mallet, Manon

    2012-01-01

    Little is known about the role of herpes simplex virus (HSV) type 1 (HSV1) in the epidemiology of genital herpes in Canada. Data on herpes viral cultures for two consecutive years obtained from L'Hôpital Dr GL Dumont, which performs all the viral culture testing in New Brunswick, were reviewed. It was hypothesized that HSV1 was the main cause of genital herpes in New Brunswick. Samples of genital origin sent to the laboratory for HSV culture testing between July 2006 and June 2008 were analyzed. Samples from an unspecified or a nongenital source were excluded from analysis. Multiple positive samples collected from the same patient were pooled into a single sample. HSV was isolated from 764 different patients. HSV1 was isolated in 62.6% of patients (male, 55%; female, 63.8%). HSV1 was isolated in 73.2% of patients 10 to 39 years of age and in 32% of patients ≥40 years of age. The difference in rates of HSV1 infection between the 10 to 39 years of age group and the ≥40 years of age group was statistically significant (Pgenital site. Significant rate differences were demonstrated between the groups 10 to 39 years of age and ≥40 years of age. Little is known about the role of herpes simplex virus (HSV) type 1 (HSV1) in the epidemiology of genital herpes in Canada. Data on herpes viral cultures for two consecutive years obtained from L’Hôpital Dr GL Dumont, which performs all the viral culture testing in New Brunswick, were reviewed. It was hypothesized that HSV1 was the main cause of genital herpes in New Brunswick. Samples of genital origin sent to the laboratory for HSV culture testing between July 2006 and June 2008 were analyzed. Samples from an unspecified or a nongenital source were excluded from analysis. Multiple positive samples collected from the same patient were pooled into a single sample. HSV was isolated from 764 different patients. HSV1 was isolated in 62.6% of patients (male, 55%; female, 63.8%). HSV1 was isolated in 73.2% of patients 10 to

  11. Bilateral symmetrical herpes zoster in an immunocompetent patient (herpes zoster duplex symmetricus)

    International Nuclear Information System (INIS)

    Arfan-ul-bari; Iftikhar, N.; Rahman, S. B.

    2003-01-01

    Herpes zoster is a common disease of adulthood. Its incidence is low in childhood and adolescence. Certain risk factors like hematological malignancies or immunosuppression due to any cause may lead to onset at an early age. There is a unilateral appearance of grouped vesicular eruption on an erythematous background which may involve contiguous dermatomes. Rarely the lesions may occur bilaterally in an otherwise healthy individual. We present a case of herpes zoster, with lesions having atypical distribution involving bilaterally symmetrical dermatomes over the lower chest.(author)

  12. Herpes Simplex Virus type 2 Infection among Females in Enugu ...

    African Journals Online (AJOL)

    BACKGROUND: Herpes simplex virus type 2 infection is life long with manifestation in a small proportion of those infected. It has presented public health concern because of its progressively increasing prevalence which some authorities say is of epidemic proportion in developing countries. Herpes simplex virus type 2 has ...

  13. Clinical and morphological characteristics of herpes zoster in south India

    Directory of Open Access Journals (Sweden)

    Dubey Anand

    2005-01-01

    Full Text Available One hundred and seven cases (6 children and 101 adults of herpes zoster were recruited over a period of two years. The frequency of herpes zoster amongst skin OPD cases was found to be 0.34 per cent. The male to female ratio was 1.74:1. The most common prodromal symptom seen was paresthesia in 25 (23.36% cases followed by itching in 21 (19.62% cases.Most common presenting complaint was pain in 97 (90.65% cases. Ninety nine cases had classical herpes zoster followed by necrotic / ulcerated herpes zoster in 5 cases and hemorrhagic herpes zoster in 3 cases. Thoracic dermatome was the most common dermatome involved in 64 (59.8% cases followed by cervical in 17 (15.8% cases. Unidermatomal involvement was seen in 81 (75.7% cases, followed by multidermatomal in 18 (16.8% cases and disseminated in 8 (7.4% cases. Forty six cases were screened for HIV, out of them; six cases (4 males, 2 females were seropositive for HIV. Classical herpes zoster was a feature in four cases; however, one case each also had necrotic and hemorrhagic form of herpes zoster. To conclude, herpes zoster commonly occurs in young adults in India with presenting symptoms such as pain, itching and fever.

  14. The Use of Iontophoretically Applied Acyclovir on Recurrent Herpes Labialis

    Science.gov (United States)

    1988-08-01

    Greenberg 1984). The varicella zoster virus causes herpes zoster and chicken pox (Kaplan 1973). Herpes simplex I (HSV-I) is responsible for the...or menstrual trouble Yes/No Skin rash, hives Yes/No Venereal disease 6 Yes/No Mumps Yes/No Measles Yes/No Chicken pox i s %6 " APPENDIX 5 76 NONNI 77

  15. The incidence of neonatal herpes in The Netherlands.

    NARCIS (Netherlands)

    Poeran, J.; Wildschut, H.; Gaytant, M.A.; Galama, J.M.D.; Steegers, E.A.P.; Meijden, W.I. van der

    2008-01-01

    BACKGROUND: In The Netherlands the incidence of neonatal herpes was 2.0-2.9 per 100,000 live births during the period 1981-1998. The low incidence warranted a rather conservative prevention policy. OBJECTIVES: To monitor for potential changes in the incidence of neonatal herpes in The Netherlands

  16. Herpes Zoster ophthalmicus and HIV seropositivity in South-south ...

    African Journals Online (AJOL)

    Herpes zoster is a painful vesiculobullous dermatitis which occurs as a result of previously established varicella zoster virus infection. It is a well established fact that Herpes zoster ophthalmicus is a well known marker of human immune deficiency virus infection even in Africans. The aim of this study is to determine if indeed ...

  17. Knowledge of genital herpes infection among antenatal clinic ...

    African Journals Online (AJOL)

    Background: Herpes simplex virus (HSV) is a major cause of genital ulcer disease worldwide and a significant factor for increased risk of acquisition and transmission of the Human Immune Deficiency Virus (HIV). The determination of the level of knowledge of genital herpes is necessary for the design and implementation of ...

  18. Frequency of Herpes Zoster Recurrence in Central District of Korea.

    Science.gov (United States)

    Ha, Jae Won; Lee, Jin Yong; Her, Young; Kim, Chul Woo; Kim, Sang Seok

    2017-10-01

    Herpes zoster is characterized by unilateral grouped vesicles along the distribution of a dermatome. A global recurrence rate as low as 0.5%∼6.2% has been reported for herpes zoster. The recurrence of herpes zoster is higher in immunocompromised patients and older patients. The purpose of this study is to assess the frequency of herpes zoster recurrence and factors that can influence its recurrence. From January 2005 to December 2015, 14,343 patients with herpes zoster were enrolled in this study. The patients were diagnosed at Hallym University Medical Centers and Kangwon National University Hospital in Seoul, Gyeonggi, and Gangwon. Herpes zoster recurrence and patient characteristics were surveyed by medical record review and a telephonic survey. The overall frequency of herpes zoster recurrence was 1.18%. The frequency of recurrence was higher in women than in men. It was also higher in patients aged 50∼70 years than in patients who were younger or older than this. Additionally, we assessed that the frequency of recurrence was statistically higher in patients with a compromised immune system and in patients who experienced longer lasting pain during their first episode. The frequency of herpes zoster recurrence is more common in women, older age, patient with longer pain duration and immunocompromised patients.

  19. Operculum syndrome: unusual feature of herpes simplex encephalitis

    NARCIS (Netherlands)

    van der Poel, J. C.; Haenggeli, C. A.; Overweg-Plandsoen, W. C.

    1995-01-01

    Herpes simplex encephalitis in adults and young patients carries a high mortality and morbidity. Its presentation may be nonspecific, sometimes hampering early diagnosis. Two young children are reported with herpes simplex encephalitis in whom the operculum syndrome was an outstanding feature. This

  20. Recombinant protein production technology

    Science.gov (United States)

    Recombinant protein production is an important technology for antibody production, biochemical activity study, and structural determination during the post-genomic era. Limiting factors in recombinant protein production include low-level protein expression, protein precipitation, and loss of protein...

  1. Childhood herpes zoster: A clustering of ten cases

    Directory of Open Access Journals (Sweden)

    Prabhu Smitha

    2009-01-01

    Full Text Available Herpes zoster occurs due to reactivation of the latent varicella zoster virus and is usually a disease of the elderly. Childhood herpes zoster is believed to be rare, though recent studies suggest increasing incidence in children. Here we report ten cases of childhood herpes zoster, seven of which occurred within a short span of six months, at a tertiary care level hospital in Pokhara, Nepal. Only three of the ten children reported previous history of varicella infection and none was immunized against varicella. Though childhood herpes zoster accounted for less than 1% of the total zoster cases in the past, recent reports show an increase in the number of cases in apparently healthy children. So far, no studies have been done linking childhood herpes zoster with HIV, though there are many studies linking it with other immunocompromised conditions.

  2. Status of prophylactic and therapeutic genital herpes vaccines.

    Science.gov (United States)

    Awasthi, Sita; Friedman, Harvey M

    2014-06-01

    A half billion people have genital herpes infections worldwide. Approximately one-fifth of American women between ages 14 and 49 are HSV-2 seropositive. The development of an effective genital herpes vaccine is a global health necessity based on the mental anguish genital herpes causes for some individuals, the fact that pregnant women with genital herpes risk transmitting infection to their newborn children, and the observation that HSV-2 infection is associated with a 3-fold to 4-fold increased probability of HIV acquisition. We review the strengths and limitations of preclinical animal models used to assess genital herpes vaccine candidates and the goals of prophylactic and therapeutic vaccines. We also discuss the current pipeline of vaccine candidates and lessons learned from past clinical trials that serve as a stimulus for new strategies, study designs and endpoint determinations. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Recidiverende erythema multiforme udløst af herpes simplex-virus

    DEFF Research Database (Denmark)

    Vestergård Grejsen, Dorthe; Henningsen, Emil

    2012-01-01

    We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described.......We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described....

  4. Managing recurrent genital herpes with acyclovir

    Directory of Open Access Journals (Sweden)

    Bedi T

    1995-01-01

    Full Text Available Seventy five patients of recurrent genital herpes (RGH treated with oral or topical acyclovir and placebo were compared and followed for periods ranging 4 to 8 years in a prospective study. Oral acyclovir definitely helps RGH patients; it shortens healing time; postpones recurrences and instills confidence in the patients. There is sufficient evidence that RGH dies a natural death with time as seen after 8 years follow up in placebo group patients. Topical use of acyclovir cream is not as useful as believed.

  5. Herpes zoster: klinik, diagnostik og behandling

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan

    2011-01-01

    Herpes zoster (HZ) is a painful vesicular rash localized to one dermatome. Post-herpetic neuralgia (PHN) is persistent pain three months after the rash started. In recent years several Cochrane reviews and clinical studies on how to treat HZ and PHN have been published. These studies show...... that early recognition and treatment can reduce acute symptoms, that antiviral therapy and corticosteroids shorten the acute illness period, that opioids and anticonvulsants have effect on acute HZ pain and, finally, that tricyclic antidepressants, opioids and anticonvulsants all have proven efficiency...

  6. Management of herpes simplex virus epithelial keratitis.

    Science.gov (United States)

    Roozbahani, Mehdi; Hammersmith, Kristin M

    2018-04-24

    To review recent advancements in the management of herpes simplex virus (HSV) epithelial keratitis. Trifluridine eye drop, acyclovir (ACV) ointment, ganciclovir gel, and oral ACV are still the main therapeutic agents. Cryopreserved amniotic membrane has been recently used as an adjuvant treatment. Resistance to ACV has become a concerning issue. The animal models of HSV vaccine are able to reduce HSV keratitis. New antivirals are under development. Current cases of HSV epithelial keratitis are manageable with available medications, but new advancements are required to decrease disease burden in the future. HSV vaccine can be revolutionary.

  7. Forebyggelse af herpes zoster med vaccination

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan

    2011-01-01

    Herpes zoster (HZ) and post-herpetic neuralgia (PHN) are frequently occurring diseases in elderly and in immuno-compromised persons. The live attenuated HZ vaccine boosts an existing immune response, so that the already established varicella-zoster virus infection is kept latent. Vaccination has...... been shown to halve the risk of HZ, and the risk of PHN is reduced by two thirds in people = 60 years. The vaccine is approved for persons aged = 50 years. However, the clinical efficacy of the vaccine is best studied in people aged = 60 years. The vaccine has so far not shown any serious side-effects....

  8. Field evaluation of safety during gestation and horizontal spread of a recombinant differential bovine herpesvirus 1 (BoHV-1 vaccine Avaliação a campo da segurança para vacas prenhes e capacidade de disseminação horizontal de uma vacina diferencial recombinante contra o Herpes-vírus Bovino tipo 1 (BoHV-1

    Directory of Open Access Journals (Sweden)

    Fernando R. Spilki

    2005-03-01

    Full Text Available Bovine herpesvirus type 1 (BoHV-1 is recognized as a major cause of respiratory, reproductive disease and abortion in cattle. Vaccination is widely applied to minimize losses induced by BoHV-1 infections; however, vaccination of dams during pregnancy with modified live virus (MLV vaccines has been occasionally associated to abortions. We have previously reported the development of a BoHV-1 recombinant virus, constructed with basis on a Brazilian BoHV-1 (Franco et al. 2002a from which the gene coding for glycoprotein E (gE was deleted (gE- by genetic manipulation. Such recombinant has been previously evaluated in its potential as a differential vaccine (gE- vaccine that allows differentiation between vaccinated and infected animals. Here, in the first part of the present study, the safety of the gE- vaccine during pregnancy was evaluated by the intramuscular inoculation of 10(7.4 tissue culture 50 % infective doses (TCID50 of the virus into 22 pregnant dams (14 BoHV-1 seronegative; 8 seropositive, at different stages of gestation. Other 15 pregnant dams were kept as non-vaccinated controls. No abortions, stillbirths or fetal abnormalities were seen after vaccination. Seroconversion was observed in both groups of previously seronegative vaccinated animals. In the second part of the study, the potential of the gE- vaccine virus to spread among beef cattle under field conditions was examined. Four heifers were inoculated intranasally with a larger amount (10(7,6 TCID50 of the gE- vaccine (to increase chances of transmission and mixed with other sixteen animals at the same age and body condition, in the same grazing area, at a population density equal to the average cattle farming density within the region (one cattle head per 10,000 m², for 180 days. All animals were monitored daily for clinical signs. Serum samples were collected on days 0, 30, 60 and 180 post-vaccination. Seroconversion was observed only in vaccinated heifers. These results

  9. Herpes simplex encephalitis in patients with cancer.

    Science.gov (United States)

    Graber, Jerome J; Rosenblum, Marc K; DeAngelis, Lisa M

    2011-11-01

    Case reports and animal models suggest that chemotherapy, corticosteroids and radiotherapy (RT) may increase the risk of herpes simplex encephalitis (HSE). We retrospectively examined cases of HSE at an academic hospital devoted to cancer care. Patients were identified by positive herpes simplex virus (HSV) polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) or by brain pathology. There were seven patients with HSE over a 12 year period, four of whom had received cranial RT. During this time, a total of 997 patients were treated with cranial RT, suggesting a greater incidence than the expected risk of two to four cases per million people per year in the general population. Five patients had recently received chemotherapy and three were on dexamethasone. MRI findings were typical; four patients had bilateral anterior temporal lesions and three had unilateral-temporal lesions. Four patients had a normal CSF white blood cell count, three of whom had prior RT and dexamethasone. Four patients were positive for HSV-1, and two for HSV-2. One patient had a negative CSF PCR for HSV, but autopsy confirmed active HSE. Though still rare, the risk of HSE may be increased in patients with cancer, especially in those receiving cranial RT. MRI findings were typical, but CSF white blood cell count was normal in four patients and one had negative CSF testing, suggesting that CSF results may be misleading in this population.

  10. Recurrent herpes labialis and HSV-1 herpes genitalis: which is the link?

    Science.gov (United States)

    Delmonte, Sergio; Sidoti, Francesca; Ribero, Simone; Dal Conte, Ivano; Curtoni, Antonio; Ciccarese, Giulia; Stroppiana, Elena; Stella, Maria L; Costa, Cristina; Cavallo, Rossana; Rebora, Alfredo; Drago, Francesco

    2017-02-08

    Recently, Herpes simplex virus (HSV)-1 seroprevalence declined among adolescents, rendering young people lacking HSV-1 antibodies more susceptible to genital HSV-1 acquisition, if sexually exposed. The aim of the present study was to identify the possible risk factors for the development of HSV-1 related herpes genitalis (HG). From January 2012 to December 2015, patients with HG attending three Sexually Transmitted Infections Units in Northern Italy were recruited. A genital swab on the lesions for the search of HSV-1/2 DNA through Real time polymerase chain reaction (PCR) and a serum sample for HSV-1/2 specific serology were performed. Moreover, patients were asked whether they had personal history of herpes labialis (HL). Patients with PCR proved HSV-1 HG were included as cases; asymptomatic subjects attending STI Units for a blood check were recruited as controls and were checked for HSV-1/2 serology. 141 cases and 70 controls were enrolled. Specific HSV-1 antibodies were found in 34.7% of the cases and 67% of the controls. History of recurrent herpes labialis (RHL) was found in 4% of the cases and 31% of the controls. The occurrence of RHL in HSV-1 seropositive patients resulted lower in the case group compared to the control group. We can speculate about a protective role for RHL against the clinical appearance of HSV-1 HG. The clinical usefulness of our study involved especially the counseling in serodiscordant couples. The presence of HSV-1 antibodies in asymptomatic sexual partners does appear protective for HG manifestation only in presence of RHL history.

  11. Recombinant clotting factors.

    Science.gov (United States)

    Pipe, Steven W

    2008-05-01

    The recombinant era for haemophilia began in the early 1980s with the cloning and subsequent expression of functional proteins for both factors VIII and IX. Efficient production of recombinant clotting factors in mammalian cell culture systems required overcoming significant challenges due to the complex post-translational modifications that were integral to their pro-coagulant function. The quick development and commercialization of recombinant clotting factors was, in part, facilitated by the catastrophic impact of viral contamination of plasma-derived clotting factor concentrates at the time. Since their transition into the clinic, the recombinant versions of both factor VIII and IX have proven to be remarkable facsimiles of their plasma-derived counterparts. The broad adoption of recombinant therapy throughout the developed world has significantly increased the supply of clotting factor concentrates and helped advance aggressive therapeutic interventions such as prophylaxis. The development of recombinant VIIa was a further advance bringing a recombinant option to haemophilia patients with inhibitors. Recombinant DNA technology remains the platform to address ongoing challenges in haemophilia care such as reducing the costs of therapy, increasing the availability to the developing world, and improving the functional properties of these proteins. In turn, the ongoing development of new recombinant clotting factor concentrates is providing alternatives for patients with other inherited bleeding disorders.

  12. Herpes,zoster with Wrist Drop and Aberrant Lesions

    Directory of Open Access Journals (Sweden)

    R K Dutta

    1987-01-01

    Full Text Available A patient having herpes zoster involving C6, 7, 8, Dl and 2 segments, developed ipsilateral wrist drop and aberrant lesions. Paralytic deformity preceded the skin eruption by one day.

  13. Herpes zoster on segmental vitiligo: Wolf’s isotopic response?

    Directory of Open Access Journals (Sweden)

    Mankesh Lal Gambhir

    2014-04-01

    Full Text Available “Wolf’s isotopic response” describes the occurrence of a new skin disorder at the site of another, unrelated and already healed skin disease. In most cases of isotopic response, the initial dermatosis is herpes zoster, herpes simplex, varicella, thrombophlebitis, scrofuloderma and striae distense. The most frequent second dermatoses are granulomatous reactions, particularly granuloma annulare, and lichenoid diseases. Various etiological reasons including viral, immunologic, neural and vascular have been put forth. We report here a case in which the second disease was herpes zoster that appeared over the same dermatomes of pre-existing segmental vitiligo. The occurrence of vitiligo as first and herpes zoster as second disease in the “Wolf’s isotopic response” has not, to the best of our knowledge, been reported previously.

  14. Fatal Neonatal Herpes Simplex Infection Likely from Unrecognized Breast Lesions.

    Science.gov (United States)

    Field, Scott S

    2016-02-01

    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 delivery of the affected baby but not recognized as possibly being caused by herpes. The baby died 9 days after birth with hepatic failure and disseminated intravascular coagulation. Peripartum health care workers need to be aware of potential nongenital (including from the breast[s]) neonatal herpes acquisition, which can be lethal. © The Author(s) 2015.

  15. [Laboratory diagnosis of genital herpes--direct immunofluorescence method].

    Science.gov (United States)

    Majewska, Anna; Romejko-Wolniewicz, Ewa; Zareba-Szczudlik, Julia; Kilijańczyk, Marek; Gajewska, Małgorzata; Młynarczyk, Grazyna

    2013-07-01

    Aim of the study was to determine clinical usefulness of direct immunofluorescence method in the laboratory diagnosis of genital herpes in women. Overall 187 anogenital swabs were collected from 120 women. Using a dacron-tipped applicator 83 swabs were collected from women suspected of genital herpes and 104 from patients with no signs of genital infection. All samples were tested using cell culture (Vero cell line) and then direct immunofluorescence method (DIF) for the identification of antigens of herpes simplex viruses: HSV-1 and HSV-2. Characteristic cytopathic effect (CPE), indicative of alphaherpesvirus infection, was observed in 43.4% of cultures with clinical specimens collected from women with suspected genital herpes and in 29.8% of cultures of clinical specimens taken from patients with no clinical symptoms of genital herpes. Herpes simplex viruses were determined in 73 samples by direct immunofluorescence method after amplification of the virus in cell culture. The DIF test confirmed the diagnosis based on the microscopic CPE observation in 85%. In 15% of samples (taken from pregnant women without clinical signs of infection) we reported positive immunofluorescence in the absence of CPE. The frequency of antigen detection was statistically significantly higher in samples that were positive by culture study (chi-square test with Yates's correction, p genital herpes in swabs taken from the vestibule of the vagina and the vulva. However, there was no statistically significant difference in the frequency of detection of Herpes Simplex Virus antigens in specimens from different parts of the genital tract in both groups of women (chi-square test, p > 0.05). In our study HHV-1 was the main causative agent of genital herpes. The growing worldwide prevalence of genital herpes, challenges with the clinical diagnosis, and availability of effective antiviral therapy are the main reasons for a growing interest in rapid, proper laboratory diagnosis of infected

  16. Genital herpes and its treatment in relation to preterm delivery.

    Science.gov (United States)

    Li, De-Kun; Raebel, Marsha A; Cheetham, T Craig; Hansen, Craig; Avalos, Lyndsay; Chen, Hong; Davis, Robert

    2014-12-01

    To examine the risks of genital herpes and antiherpes treatment during pregnancy in relation to preterm delivery (PTD), we conducted a multicenter, member-based cohort study within 4 Kaiser Permanente regions: northern and southern California, Colorado, and Georgia. The study included 662,913 mother-newborn pairs from 1997 to 2010. Pregnant women were classified into 3 groups based on genital herpes diagnosis and treatment: genital herpes without treatment, genital herpes with antiherpes treatment, and no herpes diagnosis or treatment (unexposed controls). After controlling for potential confounders, we found that compared with being unexposed, having untreated genital herpes during first or second trimester was associated with more than double the risk of PTD (odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.80, 2.76). The association was stronger for PTD due to premature rupture of membrane (OR = 3.57, 95% CI: 2.53, 5.06) and for early PTD (≤35 weeks gestation) (OR = 2.87, 95% CI: 2.22, 3.71). In contrast, undergoing antiherpes treatment during pregnancy was associated with a lower risk of PTD compared with not being treated, and the PTD risk was similar to that observed in the unexposed controls (OR = 1.11, 95% CI: 0.89, 1.38). The present study revealed increased risk of PTD associated with genital herpes infection if left untreated and a potential benefit of antiherpes medications in mitigating the effect of genital herpes infection on the risk of PTD. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    OpenAIRE

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, he...

  18. Compromiso vascular en la encefalitis herpética

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Cañas

    1997-01-01

    Full Text Available Describimos el caso de un paciente de 30 años de edad que desarrolla una encefalitis fatal par Herpes simple, en cuyos hallazgos de necropsia se destaca un compromiso vascular cerebral secundario. Se discute In posibilidad de que en la encefalitis herpética pueden presentarse dos tipos de compromiso vascular: uno reconocido desde hace tres décadas, la vasculomielinopatía diseminada, y otro, una forma de vasculitis séptica.

  19. The clinical manifestations of recurrence of genital herpes

    OpenAIRE

    ISRAILOV KHIKMATJON TUYGUNOVICH

    2016-01-01

    The clinical manifestations of genital herpes (GH) was characterized as vesicular in 67.3 % cases, in 18.2 % erosive, in 10 % erosiveulcer and in 4.5 % cases as a ulcer lesion of the skin and mucous membranes of the genitals by predisposing a massive discharge of herpes viruses into the environment and which is epidemiologically unfavorable factor due to the spreading of these viruses among the population.

  20. The calcitonin receptor gene is a candidate for regulation of susceptibility to herpes simplex type 1 neuronal infection leading to encephalitis in rat.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a fatal infection of the central nervous system (CNS predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL, Hse1, on rat chromosome 4 (confidence interval 24.3-31 Mb; LOD score 29.5 governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development.

  1. Herpes zoster ophthalmicus associated with abducens palsy

    Directory of Open Access Journals (Sweden)

    Nibrass Chaker

    2014-01-01

    Full Text Available The extraocular muscle palsies associated with herpes zoster ophthalmicus (HZO are transient, self-limiting conditions, usually seen in elderly patients. There are different treatment recommendations for paralytic complications, but prognosis has generally reported to be favorable. A 75-year-old male patient presented with diplopia. Clinical history revealed left facial vesicular eruptions and pain treated by oral aciclovir 1 week following symptom onset. On examination, we observed cicatricial lesions with crusts involving left hemiface, a limitation in abduction of the left eye, and a superficial punctuate keratitis (SPK with decreased visual acuity (4/10. Examination of the right eye was unremarkable. Hess screen test confirmed left six nerve palsy.

  2. Fluent Aphasia From Herpes Simplex Encephalitis

    Directory of Open Access Journals (Sweden)

    Fariba Yadegari

    2006-09-01

    Full Text Available The present case report introduces a patient with fluent aphasia, anterograde amnesia and anosmia due to herpes simplex encephalitis after her first delivery. The left medial temporal lobe was one of the main areas involved. On aphasia testing she showed severe anomia on both confrontation and free recall, agraphia, alexia, repetition disorder and some auditory comprehension impairments. Therapy was focused on the following issues: phonological output lexicon , using graphemes as a source of reestablishing phonological representation; describing pictures to reinforce free recall and self-cuing word retrieval strategies; sequencing the events for language memory reinforcement, etc. Results showed improvement in confrontational naming, free recall, correct responses without priming, writing on dictation, spontaneous writing and reading comprehension.

  3. MRI findings of herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Yoon, Hye Kyung; Chang, Kee Hyun; Han, Moon Hee; Kim, In One; Cha, Sang Hoon; Kim, Sang Joon

    1992-01-01

    We retrospectively analyzed the MR findings of 12 patients with herpes simplex encephalitis (HSE) (8 months - 64 years old). MR imaging was performed on either a 0.5T (6 patients) or 2.0T (6 patients) superconducting unit with spin echo pulse sequences. The most common and characteristic MR finding consisted of non-hemorrhagic lesions in the cortices of the temporal lobes(12), and insular(6), either bilateral(7) or unilateral(5). The frontal lobe and cingulate gyrus were involved in 4 and 2 patients respectively. Petechial hemorrhage was found in 3 patients. Non-hemorrhagic lesions were shown as high signal intensities on proton and T2WI, and iso- or low signal intensities on T1WI. In conclusion, MR imaging findings described above appear to be characteristic of HSE and were found to be extremely valuable in the diagnosis of HSE

  4. Herpes simplex virus encephalitis: neuroradiological diagnosis

    International Nuclear Information System (INIS)

    Struffert, T.; Reith, W.

    2000-01-01

    Herpes simplex virus encephalitis (HSE) is the most frequent viral encephalitis, as a rule with the starting point and centre within the temporal lobe. If untreated, HSE is usually fatal, thus diagnosis has to be established rapidly. Treatment with Acyclovir should begin as soon possible. As MRI is extremely sensitive in detecting the early inflammatory changes, it should be initially performed, especially as in the early stadium CT may be unspecific. We recommend the following examination protocol: coronar T1-weighted MR imaging before and after administration of gadopentetate dimeglumine, coronar FLAIR sequence and axial T2-weighted imaging. The diagnostic proof is to show the evidence of viral DNA by polymerase chain reaction (PCR) in cerebrospinal liquor. (orig.) [de

  5. [Immunopathological findings in herpes gestationis (author's transl)].

    Science.gov (United States)

    Scherer, R; Wolff, H H; Braun-Falco, O

    1977-08-12

    Herpes gestationis occurred in a 26-year-old woman during the last weeks of her second pregnancy. Within 8 days of the delivery the disease had progressed to such an extent that systemic treatment became necessary. Whereas pre-delivery treatment had consisted exclusively of local desinfection, and steroid and antibiotic ointments, treatment after delivery also included systemic use of prednisolone. After treatment for 3 weeks the skin changes had disappeared except for minimal pigmentation. Using immunofluorescent microscopy a complement activation in the dermo-epidermal junction and in adjacent clinically healthy skin could be demonstrated: There were massive linear depositions of C3, C1q and C4. In the basal membrane of the epidermis IgM could be demonstrated as an unusual finding. Further immunopathological features were found in the form of an immune complex vasculitis which could be shown during the active phase of the disease.

  6. Intracellular trafficking and maturation of herpes simplex virus type 1 gB and virus egress require functional biogenesis of multivesicular bodies.

    Science.gov (United States)

    Calistri, Arianna; Sette, Paola; Salata, Cristiano; Cancellotti, Enrico; Forghieri, Cristina; Comin, Alessandra; Göttlinger, Heinrich; Campadelli-Fiume, Gabriella; Palù, Giorgio; Parolin, Cristina

    2007-10-01

    The biogenesis of multivesicular bodies (MVBs) is topologically equivalent to virion budding. Hence, a number of viruses exploit the MVB pathway to build their envelope and exit from the cell. By expression of dominant negative forms of Vps4 and Vps24, two components of the MVB pathway, we observed an impairment in infectious herpes simplex virus (HSV) assembly/egress, in agreement with a recent report showing the involvement in HSV envelopment of Vps4, the MVB-specific ATPase (C. M. Crump, C. Yates, and T. Minson, J. Virol. 81:7380-7387). Furthermore, HSV infection resulted in morphological changes to MVBs. Glycoprotein B (gB), one of the most highly conserved glycoproteins across the Herpesviridae family, was sorted to MVB membranes. In cells expressing the dominant negative form of Vps4, the site of intracellular gB accumulation was altered; part of gB accumulated as an endoglycosidase H-sensitive immature form at a calreticulin-positive compartment, indicating that gB traffic was dependent on a functional MVB pathway. gB was ubiquitinated in both infected and transfected cells. Ubiquitination was in part dependent on ubiquitin lysine 63, a signal for cargo sorting to MVBs. Partial deletion of the gB cytoplasmic tail resulted in a dramatic reduction of ubiquitination, as well as of progeny virus assembly and release to the extracellular compartment. Thus, HSV envelopment/egress and gB intracellular trafficking are dependent on functional MVB biogenesis. Our data support the view that the sorting of gB to MVB membranes may represent a critical step in HSV envelopment and egress and that modified MVB membranes constitute a platform for HSV cytoplasmic envelopment or that MVB components are recruited to the site(s) of envelopment.

  7. DNA immunization with a herpes simplex virus 2 bacterial artificial chromosome

    International Nuclear Information System (INIS)

    Meseda, Clement A.; Schmeisser, Falko; Pedersen, Robin; Woerner, Amy; Weir, Jerry P.

    2004-01-01

    Construction of a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) is described. BAC vector sequences were inserted into the thymidine kinase gene of HSV-2 by homologous recombination. DNA from cells infected with the resulting recombinant virus was transformed into E. coli, and colonies containing the HSV-2 BAC (HSV2-BAC) were isolated and analyzed for the expected genotype. HSV2-BAC DNA was infectious when transfected back into mammalian cells and the resulting virus was thymidine kinase negative. When used to immunize mice, the HSV2-BAC DNA elicited a strong HSV-2 specific antibody response that was equal to or greater than live virus immunization. Further, HSV2-BAC immunization was protective when animals were challenged with a lethal dose of virus. The utility of the HSV2-BAC for construction of recombinant virus genomes was demonstrated by elimination of the HSV-2 glycoprotein D (gD) gene. A recombinant HSV-2 BAC with the gD gene deleted was isolated and shown to be incapable of producing infectious virus following transfection unless an HSV gD gene was expressed in a complementing cell line. Immunization of mice with the HSV2 gD-BAC also elicited an HSV-2 specific antibody response and was protective. The results demonstrate the feasibility of DNA immunization with HSV-2 bacterial artificial chromosomes for replicating and nonreplicating candidate HSV-2 vaccines, as well as the utility of BAC technology for construction and maintenance of novel HSV-2 vaccines. The results further suggest that such technology will be a powerful tool for dissecting the immune response to HSV-2

  8. Recombinant gene expression protocols

    National Research Council Canada - National Science Library

    Tuan, Rocky S

    1997-01-01

    .... A fundamental requirement for successful recombinant gene expression is the design of the cloning vector and the choice of the host organism for expression. Recombinant Gene Expression Protocols grows out of the need for a laboratory manual that provides the reader the background and rationale, as well as the practical protocols for the preparation of...

  9. Production of the R2 subunit of ribonucleotide reductase from herpes simplex virus with prokaryotic and eukaryotic expression systems: higher activity of R2 produced by eukaryotic cells related to higher iron-binding capacity.

    OpenAIRE

    Lamarche, N; Matton, G; Massie, B; Fontecave, M; Atta, M; Dumas, F; Gaudreau, P; Langelier, Y

    1996-01-01

    The R2 subunit of ribonucleotide reductase from herpes simplex virus type 2 was overproduced with prokaryotic and eukaryotic expression systems. The recombinant R2 purified by a two-step procedure exhibited a 3-fold higher activity when produced in eukaryotic cells. Precise quantification of the R2 concentration at each step of the purification indicated that the activity was not altered during the purification procedure. Moreover, we have observed that the level of R2 expression, in eukaryot...

  10. Update on Neonatal Herpes Simplex Epidemiology in the Netherlands: A Health Problem of Increasing Concern?

    NARCIS (Netherlands)

    van Oeffelen, Louise; Biekram, Manisha; Poeran, Jashvant; Hukkelhoven, Chantal; Galjaard, Sander; van der Meijden, Wim; Op de Coul, Eline

    2018-01-01

    This paper provides an update on the incidence of neonatal herpes, guideline adherence by health care professionals (HCP), and trends in genital herpes simplex virus (HSV) infection during pregnancy in the Netherlands.

  11. [Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes'

    NARCIS (Netherlands)

    Bleker, O.P.; Meijden, W.I. van der; Wittenberg, J.; Bergen, J.E. van; Boeke, A.J.; Doornum, G.J.J. van; Henquet, C.J.; Galama, J.M.D.; Postma, M.J.; Prins, J.M.; Voorst Vader, P.C. van

    2003-01-01

    The Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes' summarises the current scientific position on the diagnosis and treatment of a great number of sexually transmitted diseases (STD) and neonatal herpes. Symptomatic treatment of

  12. Genital Herpes - Initial Visits to Physicians' Offices, United States, 1966-2012

    Science.gov (United States)

    ... Data & Statistics Sexually Transmitted Diseases Figure 48. Genital Herpes — Initial Visits to Physicians’ Offices, United States, 1966 – ... page . NOTE : The relative standard errors for genital herpes estimates of more than 100,000 range from ...

  13. [Herpes simplex virus vaccine studies: from past to present].

    Science.gov (United States)

    Us, Dürdal

    2006-10-01

    The dramatical increase in the prevalence of Herpes simplex virus (HSV) infections and the significant physical and psychosocial morbidity of HSV type 2 infections, generate the need for an efficacious HSV vaccine. The most important properties of HSVs that should be targeted for a successful vaccine are neuronal invasion, latency and reactivation in spite of specific host immune responses. The major expectation for an ideal HSV vaccine candidate is to induce sterilizing immunity, which must be effective at all portals of HSV entry; to prevent or reduce the symptomatic disease and to eliminate or at least to limit the asymptomatic viral shedding. The first vaccine studies have began in the 1920s and in the intervening eight decades there have been many attempts to develop an effective one. Although encouraging findings came from experiments in various animal models, human studies have been disappointing, unfortunately. The vaccine strategies that have undergone clinical evaluation until today included autoinoculation of live HSV, whole inactivated vaccines, attenuated live virus vaccines, modified live virus subunit vaccines, cell culture-derived subunit vaccines, recombinant subunit (glycoprotein) vaccines, DISC (Disabled Infectious Single Cycle) virus vaccines, viral vectors and naked DNA vaccines. In most of the clinical studies the failure of HSV vaccines in spite of inducing very high levels of specific neutralizing antibodies have emphasized that cell-mediated immune response, especially Thl type immunity is important in preventing both primary disease and recurrences with HSV, rather than humoral response. The most hopeful result was obtained with HSV-2 gD and alum/MPL vaccine in clinical studies. This vaccine was found 74% effective in preventing genital disease in HSV seronegative women but was not effective in men or seropositive women. In recent years it is possible to genetically engineer HSV to produce a vaccine strain that is protective without

  14. Tumores perianais provocados pelo herpes simples Perianal tumors provoked by herpes simplex

    Directory of Open Access Journals (Sweden)

    Sidney Roberto Nadal

    2007-03-01

    Full Text Available O Herpes simplex (HSV é um DNA vírus que provoca afecções perianais, sendo considerada a causa mais comum das úlceras na região. Apesar da forma ulcerativa ser a mais conhecida, a literatura relata o aparecimento de lesões tumorais, nodulares ou hipertróficas relacionadas ao vírus. O exame proctológico mostra tumores dolorosos, achatados, com superfície recoberta por ulceração rasa e com bordas bem delimitadas, elevadas e lobuladas, localizados na margem anal e/ou no sulco interglúteo, algumas vezes imitando condilomas virais ou carcinoma. A anamnese revela instalação insidiosa com crescimento lento e progressivo, além da história de tratamentos anteriores para úlceras herpéticas. O diagnóstico diferencial com carcinoma impõe a realização de biópsia para confirmação histológica. Esse exame revela hiperplasia epitelial moderada e denso processo inflamatório com linfócitos e plasmócitos. Células gigantes e multinucleadas são observadas na epiderme. Os testes imunohistoquímicos sugerem o HSV. A opção terapêutica inicial deve ser o tratamento medicamentoso. Importante definir o diagnóstico etiológico para aliviar o desconforto e evitar operação radical desnecessária, e introduzir medicação anti-retroviral nos portadores do HIV para melhora da imunidade.Herpes simplex is a DNA virus which provokes perianal lesions, and it is the most frequent etiology of anal ulcer. Despite the ulcerative herpes being known worldwide, literature relates a tumoral, or nodular, or hypertrophic form related to this virus. Proctological examination showed nodules with a verrucous appearance and an ulcerated surface at the anal margin, sometimes mimicking viral condylomas or carcinomas. Anamnesis reveals insidious installation, slow growth and prior treatments for herpetic ulcers. The differential diagnoses with cancer allow us to perform biopsies for histological confirmation. This exam reveals mild epithelial hyperplasia and

  15. Cold Sore, Cold Soul? An Examination of Orolabial Herpes in Film

    OpenAIRE

    Alex C. HOLLIDAY; Amanda SALIH; Richard F. Jr. WAGNER

    2016-01-01

    [EN] The sociocultural phenomenon of herpes is attributed to two strains of the herpes simplex virus: herpes simplex virus type 1 (HSV-1) causes orolabial cold sores while herpes simplex virus type 2 (HSV-2) is typically identified in genital lesions, though both viruses may cause clinically similar signs and symptoms anywhere in or on the body. While these infections are extremely prevalent and typically benign, media sources such as film have perpetuated a negative public percep...

  16. Latent Herpes Viruses Reactivation in Astronauts

    Science.gov (United States)

    Mehta, Satish K.; Pierson, Duane L.

    2008-01-01

    Space flight has many adverse effects on human physiology. Changes in multiple systems, including the cardiovascular, musculoskeletal, neurovestibular, endocrine, and immune systems have occurred (12, 32, 38, 39). Alterations in drug pharmacokinetics and pharmacodynamics (12), nutritional needs (31), renal stone formation (40), and microbial flora (2) have also been reported. Evidence suggests that the magnitude of some changes may increase with time in space. A variety of changes in immunity have been reported during both short (.16 days) and long (>30 days) space missions. However, it is difficult to determine the medical significance of these immunological changes in astronauts. Astronauts are in excellent health and in superb physical condition. Illnesses in astronauts during space flight are not common, are generally mild, and rarely affect mission objectives. In an attempt to clarify this issue, we identified the latent herpes viruses as medically important indicators of the effects of space flight on immunity. This chapter demonstrates that space flight leads to asymptomatic reactivation of latent herpes viruses, and proposes that this results from marked changes in neuroendocrine function and immunity caused by the inherent stressfullness of human space flight. Astronauts experience uniquely stressful environments during space flight. Potential stressors include confinement in an unfamiliar, crowded environment, isolation, separation from family, anxiety, fear, sleep deprivation, psychosocial issues, physical exertion, noise, variable acceleration forces, increased radiation, and others. Many of these are intermittent and variable in duration and intensity, but variable gravity forces (including transitions from launch acceleration to microgravity and from microgravity to planetary gravity) and variable radiation levels are part of each mission and contribute to a stressful environment that cannot be duplicated on Earth. Radiation outside the Earth

  17. The negative association between a history of recurrent herpes labialis and cervical neoplasia

    NARCIS (Netherlands)

    Burger, M. P.; Wilterdink, J. B.

    1988-01-01

    We considered the possibility that herpetic recurrences and herpes virus associated neoplasia are mutually exclusive disorders because they are expressions of different herpes virus-host relationships. We assumed that the human body copes with orofacial and genital herpes infections in the same

  18. Herpes zoster, immunological deterioration and disease progression in HIV-1 infection

    NARCIS (Netherlands)

    Veenstra, J.; Krol, A.; van Praag, R. M.; Frissen, P. H.; Schellekens, P. T.; Lange, J. M.; Coutinho, R. A.; van der Meer, J. T.

    1995-01-01

    OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied.

  19. [Clinical, epidemiological, and etiological studies of adult aseptic meningitis: a report of 12 cases of herpes simplex meningitis, and a comparison with cases of herpes simplex encephalitis].

    Science.gov (United States)

    Himeno, Takahiro; Shiga, Yuji; Takeshima, Shinichi; Tachiyama, Keisuke; Kamimura, Teppei; Kono, Ryuhei; Takemaru, Makoto; Takeshita, Jun; Shimoe, Yutaka; Kuriyama, Masaru

    2018-01-26

    We treated 437 cases of adult aseptic meningitis and 12 cases (including 2 recurrent patients; age, 31.8 ± 8.9 years; 7 females) of herpes simplex meningitis from 2004 to 2016. The incidence rate of adult herpes simplex meningitis in the cases with aseptic meningitis was 2.7%. One patient was admitted during treatment of genital herpes, but no association was observed between genital herpes and herpes simplex meningitis in the other cases. The diagnoses were confirmed in all cases as the cerebrospinal fluid (CSF) was positive for herpes simplex virus (HSV)-DNA. For diagnosis confirmation, the DNA test was useful after 2-7 days following initial disease onset. Among other types of aseptic meningitis, the patients with herpes simplex meningitis showed relatively high white blood cell counts and relatively high CSF protein and high CSF cell counts. CSF cells showed mononuclear cell dominance from the initial stage of the disease. During same period, we also experienced 12 cases of herpes simplex encephalitis and 21 cases of non-hepatic acute limbic encephalitis. Notably, the patients with herpes simplex meningitis were younger and their CSF protein and cells counts were higher than those of the patients with herpes simplex encephalitis.

  20. Hadron correlations from recombination

    Energy Technology Data Exchange (ETDEWEB)

    Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

    2005-01-01

    Quark recombination is a successful model to describe the hadronization of a deconfined quark gluon plasma. Jet-like dihadron correlations measured at RHIC provide a challenge for this picture. We discuss how correlations between hadrons can arise from correlations between partons before hadronization. An enhancement of correlations through the recombination process, similar to the enhancement of elliptic flow is found. Hot spots from completely or partially quenched jets are a likely source of such parton correlations.

  1. Pityriasis Lichenoides Chronica Associated with Herpes Simplex Virus Type 2

    Directory of Open Access Journals (Sweden)

    Antonio Javier González Rodríguez

    2012-01-01

    Full Text Available Introduction. Pityriasis lichenoides is a rare, acquired spectrum of skin conditions of an unknown etiology. Case Report. A 28-year-old man presented with recurrent outbreaks of herpes simplex virus associated with the onset of red-to-brown maculopapules located predominantly in trunk in each recurrence. Positive serologies to herpes simplex virus type 2 were detected. Histopathological examination of one of the lesions was consistent with a diagnosis of pityriasis lichenoides chronica. Discussion. Pityriasis lichenoides is a rare cutaneous entity of an unknown cause which includes different clinical presentations. A number of infectious agents have been implicated based on the clustering of multiple outbreaks and elevated serum titers to specific pathogens (human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, and herpes simplex virus. In our patient, resolution of cutaneous lesions coincided with the administration of antiviral drugs and clinical improvement in each genital herpes recurrence. In conclusion, we report a case in which cutaneous lesions of pityriasis lichenoides chronica and a herpes simplex virus-type 2-mediated disease have evolved concomitantly.

  2. Herpes zoster: A clinical study in 205 patients

    Directory of Open Access Journals (Sweden)

    E N Abdul Latheef

    2011-01-01

    Full Text Available Background: Even though herpes zoster is a common condition its incidence and pattern of occurrence in the era of HIV disease is significant. Aim: To analyze the incidence, pattern of occurrence and evolution of herpes zoster with special attention to provocative factors if any. Materials and Method s: This was an analytical study conducted for 2 years based on a preformed proforma containing preliminary information, a detailed clinical evaluation regarding the segment of involvement, morphology, pattern of lesions, complications, disseminations etc. and investigations to establish provocative factors if any. Results: Incidence of herpes zoster was mainly in the fourth and third decades of life. A definite history of chicken pox was present in only 63.4% cases. In the majority (70% herpes zoster occurred spontaneously. In 30% cases, immunosuppression due to chemotherapy, malignancy, HIV infection, diabetes mellitus were observed. The commonest segment affected was thoracic (42.4% followed by cranial (28.2% and cervical (12.1%. Majority resolved in 7-14 days except immunosuppressed. 34.6% of the patients had complications such as secondary bacterial infection, post herpetic neuralgia, and motor weakness. Ten patients had HIV infection as a provocative factor. Conclusion: The results of incidence and clinical pattern of herpes zoster is almost parallel to the previous studies. Any factors of immunosuppression should be checked, especially HIV, particularly in disseminated and long-lasting cases.

  3. Herp enhances ER-associated protein degradation by recruiting ubiquilins

    International Nuclear Information System (INIS)

    Kim, Tae-Yeon; Kim, Eunmin; Yoon, Sungjoo Kim; Yoon, Jong-Bok

    2008-01-01

    ER-associated protein degradation (ERAD) is a protein quality control system of ER, which eliminates misfolded proteins by proteasome-dependent degradation and ensures export of only properly folded proteins from ER. Herp, an ER membrane protein upregulated by ER stress, is implicated in regulation of ERAD. In the present study, we show that Herp interacts with members of the ubiquilin family, which function as a shuttle factor to deliver ubiquitinated substrates to the proteasome for degradation. Knockdown of ubiquilin expression by small interfering RNA stabilized the ERAD substrate CD3δ, whereas it did not alter or increased degradation of non-ERAD substrates tested. CD3δ was stabilized by overexpressed Herp mutants which were capable of binding to ubiquilins but were impaired in ER membrane targeting by deletion of the transmembrane domain. Our data suggest that Herp binding to ubiquilin proteins plays an important role in the ERAD pathway and that ubiquilins are specifically involved in degradation of only a subset of ubiquitinated targets, including Herp-dependent ERAD substrates

  4. Computer tomography in herpes simplex encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Hacke, W.; Zeumer, H.

    1981-10-01

    The CT findings in six patients with confirmed herpes simplex encephalitis were analysed and compared with the literature. Thirty-four examinations were performed, 27 within the first 14 days of the illness. The early findings show three characteristic features: The CT may be entirely normal up to the fourth day. Consistent with clinical and E.E.G. findings there then develops a hypodense temporal lesion which, even at this stage, acts as an expanding lesion in half the patients. Between the sixth and eighth day there is frequently involvement of the contra-lateral temporal lobe, not as a continuation, but as a new lesion. At the same time, or after several days, there is involvement of the basal portions of the frontal lobes. In this late phase there may be necrosis in the basal ganglia, thalamus or other parts of the brain. The CT findings in this late phase are uniform and characteristic of the disease. For early diagnosis and treatment the early clinical, electrophysiological and neuro-radiological findings are important. A normal CT scan two days after the onset of clinical symptoms may be regarded as significant.

  5. Computer tomography in herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Hacke, W.; Zeumer, H.

    1981-01-01

    The CT findings in six patients with confirmed herpes simplex encephalitis were analysed and compared with the literature. Thirty-four examinations were performed, 27 within the first 14 days of the illness. The early findings show three characteristic features: The CT may be entirely normal up to the fourth day. Consistent with clinical and E.E.G. findings there then develops a hypodense temporal lesion which, even at this stage, acts as an expanding lesion in half the patients. Between the sixth and eighth day there is frequently involvement of the contra-lateral temporal lobe, not as a continuation, but as a new lesion. At the same time, or after several days, there is involvement of the basal portions of the frontal lobes. In this late phase there may be necrosis in the basal ganglia, thalamus or other parts of the brain. The CT findings in this late phase are uniform and characteristic of the disease. For early diagnosis and treatment the early clinical, electrophysiological and neuro-radiological findings are important. A normal CT scan two days after the onset of clinical symptoms may be regarded as significant. (orig.) [de

  6. Inhibition of MHC class I is a virulence factor in herpes simplex virus infection of mice.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Herpes simplex virus (HSV has a number of genes devoted to immune evasion. One such gene, ICP47, binds to the transporter associated with antigen presentation (TAP 1/2 thereby preventing transport of viral peptides into the endoplasmic reticulum, loading of peptides onto nascent major histocompatibility complex (MHC class I molecules, and presentation of peptides to CD8 T cells. However, ICP47 binds poorly to murine TAP1/2 and so inhibits antigen presentation by MHC class I in mice much less efficiently than in humans, limiting the utility of murine models to address the importance of MHC class I inhibition in HSV immunopathogenesis. To address this limitation, we generated recombinant HSVs that efficiently inhibit antigen presentation by murine MHC class I. These recombinant viruses prevented cytotoxic T lymphocyte killing of infected cells in vitro, replicated to higher titers in the central nervous system, and induced paralysis more frequently than control HSV. This increase in virulence was due to inhibition of antigen presentation to CD8 T cells, since these differences were not evident in MHC class I-deficient mice or in mice in which CD8 T cells were depleted. Inhibition of MHC class I by the recombinant viruses did not impair the induction of the HSV-specific CD8 T-cell response, indicating that cross-presentation is the principal mechanism by which HSV-specific CD8 T cells are induced. This inhibition in turn facilitates greater viral entry, replication, and/or survival in the central nervous system, leading to an increased incidence of paralysis.

  7. The Laboratory Diagnosis of Herpes Simplex Virus Infections

    Directory of Open Access Journals (Sweden)

    Ameeta Singh

    2005-01-01

    Full Text Available Herpes simplex virus (HSV types 1 and 2 cause genital herpes infections and are the most common cause of genital ulcer disease in industrialized nations. Although these infections are very common, the majority of them remain underdiagnosed because they are asymptomatic or unrecognized. A clinical diagnosis of genital herpes should always be confirmed by laboratory testing; this can be accomplished through the use of direct tests for viral isolation, the detection of antigen or, more recently, the detection of HSV DNA using molecular diagnostic techniques. Testing for serotypes is recommended because of the different prognostic and counselling implications. Type-specific HSV serology is becoming more readily available and will enhance the ability to make the diagnosis and guide clinical management in select patients.

  8. Herpes Zoster Duplex Unilateralis: Two Cases and Brief Literature Review.

    Science.gov (United States)

    Son, Jee Hee; Chung, Bo Young; Kim, Hye One; Cho, Hee Jin; Park, Chun Wook

    2016-12-01

    Cases involving dermatomal herpes zoster in two or more locations are rare, especially in immunocompetent patients. When two noncontiguous dermatomes are involved, if affected unilaterally, it is called herpes zoster duplex unilateralis; if bilaterally, bilateralis. Here, we report two cases of herpes zoster duplex unilateralis. A 66-year-old man presented with painful erythematous grouped vesicles on his left scalp, forehead, trunk, and back (left [Lt.] V1, Lt. T8). Histologic findings were consistent with herpetic infection. A 33-year-old woman presented with painful erythematous grouped vesicles and crust on her left forehead and neck (Lt. V1, Lt. C5). Both patients were treated with oral administration of famcyclovir 750 mg/day for seven days.

  9. Herpes zoster infection of maxillary nerve: A case report

    Directory of Open Access Journals (Sweden)

    Isha Thakur

    2017-01-01

    Full Text Available Herpes zoster of the trigeminal nerve branches caused by varicella zoster is a clinical entity consisting of erythematous macules, papules, vesicles, bullae, small ulcers and erythematous plaques, with characteristic short acute/pre-eruptive phases and long herpetic periods with pain. It is caused by reactivation of latent varicella infection. Herpes zoster is a less common endemic disease compared to varicella. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist. Emergency treatment for a misdiagnosis such as trigeminal neuralgia, odontalgia, and acute pulpitis, as well as complications reported in literature such as tooth resorption, periapical lesions, periodontal destructions, and osteomyelitis may cause an irreversible damage to the patient. Hence, the dentist must be familiar with the presenting signs and symptoms in prodrome of herpes zoster infection of trigeminal nerve. The present article focuses on the pathogenesis, clinical picture, difficulties in diagnosis and management of such cases.

  10. Herpes Simplex Mastitis: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Holly Brown

    1996-01-01

    Full Text Available The most common sites of herpes simplex virus (HSV infection are around the oral cavity and the genitalia. However, HSV can infect any skin or mucous membrane surface. One uncommon site of HSV infection is the breast. Reports of herpetic breast infections are predominantly cases of transmission from a systemically HSV-infected neonate to the mother during breast-feeding. A review of the literature identified only six reports suggesting HSV breast lesions acquired by means other than through an infected infant. Of these, only one report suggests HSV transmission to the breast from a male sexual partner. A second case of clinically unsuspected symptomatic herpes mastitis presumably acquired from sexual contact in a 46-year-old woman is presented. Herpes simplex type 1 was isolated by using polymerase chain reaction and restriction fragment length polymerization techniques. The purpose of this report is to alert physicians to HSV mastitis.

  11. The Impact of Pharmacist Interventions on Herpes Zoster Vaccination Rates.

    Science.gov (United States)

    Eid, Deeb D; Meagher, Rebecca C; Lengel, Aaron J

    2015-08-01

    The Centers for Disease Control and Prevention found that in 2010 only 14.4% of people in the United States who are appropriate candidates received the herpes zoster (shingles) vaccine. This manuscript highlights recent studies that investigate how pharmacists can help improve vaccination rates of herpes zoster in the geriatric population. Research has demonstrated that face-to-face interaction, education, and outreach by pharmacists in the community can help improve rates of herpes zoster vaccination. Having pharmacists take time to talk with patients about the vaccine was shown to have a positive impact on vaccine rates. When face-to-face interactions are not feasible, promotional materials such as newspaper advertisements, flyers, and personalized letters were also found to have a beneficial impact. Pharmacists should consider ways to increase awareness of vaccinations and directly encourage their patients to be vaccinated.

  12. Recurrent herpes zoster in a child with SLE

    Directory of Open Access Journals (Sweden)

    Jain C

    1995-01-01

    Full Text Available A 12-year-old girl had systemic lupus erythematosus (SLE and type IV lupus nephritis since three-and-a-half years. She was treated with prednisolone and cyclophosphamide. She had first attack of herpes zoster (HZ involving eighth and ninth thoracic segments on right side at the age of nine years. Second attack occurred on the same segments on same side at the age of twelve years. The second attack of herpes zoster was treated with oral acyclovir 400 mg five times a day for seven days plus analgesics and multi-vitamins. Most probably this is the first case of recurrent herpes zoster (RHZ in a child in Indian literature.

  13. Radiation enhaced reactivation of herpes simplex virus: effect of caffeine

    International Nuclear Information System (INIS)

    Hellman, K.B.; Lytle, C.D.; Bockstahler, L.E.

    1976-01-01

    Ultraviolet enhanced (Weigle) reactivation of UV-irradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cell monolayers was decreased by caffeine. X-ray enhanced reactivation of UV-irradiated virus in X-irradiated monolayers (X-ray reactivation) and UV- or X-ray-inactivated capacity of the cells to support unirradiated virus plaque formation were unaffected by caffeine. The results suggest that a caffeine-sensitive process is necessary for the expression of Weigle reactivation for herpes virus. Since caffeine did not significantly affect X-ray reactivation, different mechanisms may be responsible for the expression of Weigle reactivation and X-ray reactivation

  14. Radiation enhanced reactivation of herpes simplex virus: effect of caffeine.

    Science.gov (United States)

    Hellman, K B; Lytle, C D; Bockstahler, L E

    1976-09-01

    Ultaviolet enhanced (Weigle) reactivation of UV-irradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cell monolayers was decreased by caffeine. X-ray enhanced reactivation of UV-irradiated virus in X-irradiated monolayers (X-ray reactivation) and UV- or X-ray-inactivated capacity of the cells to support unirradiated virus plaque formation were unaffected by caffeine. The results suggest that a caffeine-sensitive process is necessary for the expression of Weigle reactivation for herpes virus. Since cafeine did not significantly affect X-ray reactivation, different mechanisms may be responsible for the expression of Weigle reactivation and X-ray reactivation.

  15. 2017 European guidelines for the management of genital herpes.

    Science.gov (United States)

    Patel, Rajul; Kennedy, Oliver J; Clarke, Emily; Geretti, Anna; Nilsen, Arvid; Lautenschlager, Stephan; Green, John; Donders, Gilbert; van der Meijden, Willem; Gomberg, Mikhail; Moi, Harald; Foley, Elizabeth

    2017-12-01

    Genital herpes is one of the commonest sexually transmitted infections worldwide. Using the best available evidence, this guideline recommends strategies for diagnosis, management, and follow-up of the condition as well as for minimising transmission. Early recognition and initiation of therapy is key and may reduce the duration of illness or avoid hospitalisation with complications, including urinary retention, meningism, or severe systemic illness. The guideline covers a range of common clinical scenarios, such as recurrent genital herpes, infection during pregnancy, and co-infection with human immunodeficiency virus.

  16. Optimization of Herpes Virus Infection Treatment in Children

    Directory of Open Access Journals (Sweden)

    Yu.P. Kharchenko

    2012-03-01

    There was revealed the polymorphism of human herpes virus 6 in children associated with virus replication activity. The important role of chronic human herpes virus 6 in forming of sickly children group with involvement of nervous and cardiovascular systems and presence of the various clinical variants correlating with the form of an infection contamination is confirmed. Principles of stratification of patients, diagnostic and treatment approaches with account of clinical semiology and complex of molecular-genetic, serological, bacteriological, neurofunctional and cardiovascular examinations were developed. The treatment positive results allow to confirm the benefit from integrative multidisciplinary therapy.

  17. Regulation of Meiotic Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gregory p. Copenhaver

    2011-11-09

    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  18. Activated MEK Suppresses Activation of PKR and Enables Efficient Replication and In Vivo Oncolysis by Δγ134.5 Mutants of Herpes Simplex Virus 1

    Science.gov (United States)

    Smith, Kerrington D.; Mezhir, James J.; Bickenbach, Kai; Veerapong, Jula; Charron, Jean; Posner, Mitchell C.; Roizman, Bernard; Weichselbaum, Ralph R.

    2006-01-01

    Herpes simplex virus mutants lacking the γ134.5 gene are not destructive to normal tissues but are potent cytolytic agents in human tumor cells in which the activation of double-stranded RNA-dependent protein kinase (PKR) is suppressed. Thus, replication of a Δγ134.5 mutant (R3616) in 12 genetically defined cancer cell lines correlates with suppression of PKR but not with the genotype of RAS. Extensive analyses of two cell lines transduced with either dominant negative MEK (dnMEK) or constitutively active MEK (caMEK) indicated that in R3616 mutant-infected cells dnMEK enabled PKR activation and decreased virus yields, whereas caMEK suppressed PKR and enabled better viral replication and cell destruction in transduced cells in vitro or in mouse xenografts. The results indicate that activated MEK mediates the suppression of PKR and that the status of MEK predicts the ability of Δγ134.5 mutant viruses to replicate in and destroy tumor cells. PMID:16414988

  19. Herpes Simplex Virus Infection Mimicking Bullous Disease in an Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Anne L.Y. Lecluse

    2010-06-01

    Full Text Available Immunodeficient patients are at risk of developing extended or atypical herpes simplex virus infections, which can be easily misdiagnosed. We present the case of a 79-year-old, treatment-induced (oral corticosteroid, immunocompromised female with an extensive atypical herpes simplex virus infection. This patient presented with multiple erosions and vesicles on the trunk with a subacute onset. The clinical differential diagnosis was herpes simplex infection, herpes zoster infection, pemphigus vulgaris or bullous pemphigoid. Due to the atypical clinical presentation and negative Tzanck test, suspicion of viral infection was low. High-dose steroid treatment was initiated. Subsequent histopathology, however, showed a herpes simplex virus infection. After discontinuing steroid treatment and initiating antiviral treatment, the patient recovered within a week. Emphasis must be placed on the importance of clinical awareness of extended and clinically atypical herpes simplex infections in immunocompromised patients. A negative Tzanck test does not rule out the possibility of a herpes infection.

  20. Cold Sore, Cold Soul? An Examination of Orolabial Herpes in Film

    Directory of Open Access Journals (Sweden)

    Alex C. HOLLIDAY

    2016-04-01

    Full Text Available The sociocultural phenomenon of herpes is attributed to two strains of the herpes simplex virus: herpes simplex virus type 1 (HSV-1 causes orolabial cold sores while herpes simplex virus type 2 (HSV-2 is typically identified in genital lesions, though both viruses may cause clinically similar signs and symptoms anywhere in or on the body. While these infections are extremely prevalent and typically benign, media sources such as film have perpetuated a negative public perception of the disease. Thus, a large portion of society continues to associate these conditions with sexual misconduct and moral failing. Despite decades of available antiviral therapy to shorten and suppress outbreaks, movies continue to exploit herpes for degradation and for humor. Portrayal of genital herpes in films is avoided in order to avert unnecessary and grotesque nude scenes, so depictions of cold sores are preferred. This article analyzes the use of orolabial herpes lesions in selected English language films released from 1984-2012.

  1. Increasing trends of herpes zoster in Australia.

    Directory of Open Access Journals (Sweden)

    Raina MacIntyre

    Full Text Available Increasing trends in incidence of herpes zoster (HZ have been reported in Australia and internationally. This may reflect the impact of childhood VZV vaccination programs introduced universally in Australia in late 2005. The objective of this study was to evaluate changes in incidence of HZ and PHN in Australia over time, and associated healthcare resource utilisation.Australian data on general practice (GP encounters for HZ, specific antiviral prescribing data from the pharmaceutical benefits scheme, emergency department presentations from the states of NSW and Victoria and national hospitalisation data for HZ were analysed for time trends using regression models. Two time periods (2000-2006 and 2006-2013 were compared which correspond broadly with the pre- and post- universal VZV vaccination period.All data sources showed increasing rates of HZ with age and over time. The GP database showed a significant annual increase in encounters for HZ of 2.5 per 100,000 between 1998 and 2013, and the rates of prescriptions for HZ increased by 4.2% per year between 2002 and 2012. In the 60+ population HZ incidence was estimated to increase from 11.9 to 15.4 per 1,000 persons using GP data or from 12.8 to 14.2 per 1,000 persons using prescription data (p<0.05, between the two periods. Hospitalisation data did not show the same increasing trend over time, except for the age group ≥80 years. Most emergency visits for HZ were not admitted, and showed significant increases over time.The burden of HZ in Australia is substantial, and continues to increase over time. This increase is seen both pre- and post-universal VZV vaccination in 2005, and is most prominent in the older population. The substantial burden of HZ, along with ageing of the Australian population and the importance of healthy ageing, warrants consideration of HZ vaccination for the elderly.

  2. Adult herpes simplex encephalitis: fifteen years' experience.

    Science.gov (United States)

    Riera-Mestre, Antoni; Gubieras, Laura; Martínez-Yelamos, Sergio; Cabellos, Carmen; Fernández-Viladrich, Pedro

    2009-03-01

    Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults. The aim of this study is to describe the characteristics of HSE and the factors influencing its outcome. Retrospective study of patients diagnosed with HSE in a tertiary care teaching hospital over a 15-year period. Diagnosis was based on a consistent clinical profile for HSE, plus either a PCR-positive CSF HSV study or consistent brain neuroimaging findings. Patients were divided into 2 groups according to the modified Rankin Scale: good outcome (Grades =3). Thirty-five patients were included. Mean age was 53.9 years. More than half presented febricula or fever, headache, disorientation, behavioral changes, decreased level of consciousness, or neurological deficit. CSF glucose concentration was normal in all patients and WBC count was normal in 8 (23%). PCR for HSV was positive in 92% and cranial MRI was suggestive of HSE in 100% of patients. Mortality was 8.6%. In relation to outcome, age (OR=1.079; 95% CI, 1.023-1.138) and serum albumin level at admission (OR=0.87; 95% CI, 0.794-0.954) were independent prognostic factors at discharge. At 6 months, days of fever after initiation of acyclovir therapy (OR=1.219; 95% CI, 1.046-1.422) and serum albumin level at admission (OR=0.917; 95% CI, 0.87-0.967) were independent prognostic factors. Normal brain MRI or detection of low CSF glucose concentration requires consideration of diagnoses other than HSE. Age, serum albumin level at admission, and days of fever after initiation of acyclovir therapy were independent prognostic factors of the disease.

  3. Calcium spirulan derived from Spirulina platensis inhibits herpes simplex virus 1 attachment to human keratinocytes and protects against herpes labialis.

    Science.gov (United States)

    Mader, Julia; Gallo, Antonio; Schommartz, Tim; Handke, Wiebke; Nagel, Claus-Henning; Günther, Patrick; Brune, Wolfram; Reich, Kristian

    2016-01-01

    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. We investigated the antiviral activity of a defined Spirulina platensis microalga extract and of purified calcium spirulan (Ca-SP), a sulfated polysaccharide contained therein. The inhibitory effects of HSV-1 were assessed by using a plaque reduction assay and quantitative PCR in a susceptible mammalian epithelial cell line and confirmed in human keratinocytes. Time-of-addition and attachment experiments and fluorescence detection of the HSV-1 tegument protein VP16 were used to analyze the mechanism of HSV-1 inhibition. Effects of Ca-SP on Kaposi sarcoma-associated herpesvirus/human herpes virus 8 replication and uptake of the ORF45 tegument protein were tested in human retinal pigment epithelial cells. In an observational trial the prophylactic effects of topically applied Ca-SP were compared with those of systemic and topical nucleoside analogues in 198 volunteers with recurrent herpes labialis receiving permanent lip makeup. Ca-SP inhibited HSV-1 infection in vitro with a potency at least comparable to that of acyclovir by blocking viral attachment and penetration into host cells. Ca-SP also inhibited entry of Kaposi sarcoma-associated herpesvirus/human herpes virus 8. In the clinical model of herpes exacerbation, the prophylactic effect of a Ca-SP and microalgae extract containing cream was superior to that of acyclovir cream. These data indicate a potential clinical use of Ca-SP containing Spirulina species extract for the prophylactic treatment of herpes labialis and suggest possible activity of Ca-SP against infections caused by other herpesviruses. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Gateway Recombinational Cloning.

    Science.gov (United States)

    Reece-Hoyes, John S; Walhout, Albertha J M

    2018-01-02

    The Gateway recombinatorial cloning system was developed for cloning multiple DNA fragments in parallel (e.g., in 96-well formats) in a standardized manner using the same enzymes. Gateway cloning is based on the highly specific integration and excision reactions of bacteriophage λ into and out of the Escherichia coli genome. Because the sites of recombination (" att " sites) are much longer (25-242 bp) than restriction sites, they are extremely unlikely to occur by chance in DNA fragments. Therefore, the same recombination enzyme can be used to robustly clone many different fragments of variable size in parallel reactions. © 2018 Cold Spring Harbor Laboratory Press.

  5. The Basic Domain of Herpes Simplex Virus 1 pUS9 Recruits Kinesin-1 To Facilitate Egress from Neurons.

    Science.gov (United States)

    Diefenbach, Russell J; Davis, April; Miranda-Saksena, Monica; Fernandez, Marian A; Kelly, Barbara J; Jones, Cheryl A; LaVail, Jennifer H; Xue, Jing; Lai, Joey; Cunningham, Anthony L

    2016-02-15

    The alphaherpesviral envelope protein pUS9 has been shown to play a role in the anterograde axonal transport of herpes simplex virus 1 (HSV-1), yet the molecular mechanism is unknown. To address this, we used an in vitro pulldown assay to define a series of five arginine residues within the conserved pUS9 basic domain that were essential for binding the molecular motor kinesin-1. The mutation of these pUS9 arginine residues to asparagine blocked the binding of both recombinant and native kinesin-1. We next generated HSV-1 with the same pUS9 arginine residues mutated to asparagine (HSV-1pUS9KBDM) and then restored them being to arginine (HSV-1pUS9KBDR). The two mutated viruses were analyzed initially in a zosteriform model of recurrent cutaneous infection. The primary skin lesion scores were identical in severity and kinetics, and there were no differences in viral load at dorsal root ganglionic (DRG) neurons at day 4 postinfection (p.i.) for both viruses. In contrast, HSV-1pUS9KBDM showed a partial reduction in secondary skin lesions at day 8 p.i. compared to the level for HSV-1pUS9KBDR. The use of rat DRG neuronal cultures in a microfluidic chamber system showed both a reduction in anterograde axonal transport and spread from axons to nonneuronal cells for HSV-1pUS9KBDM. Therefore, the basic domain of pUS9 contributes to anterograde axonal transport and spread of HSV-1 from neurons to the skin through recruitment of kinesin-1. Herpes simplex virus 1 and 2 cause genital herpes, blindness, encephalitis, and occasionally neonatal deaths. There is also increasing evidence that sexually transmitted genital herpes increases HIV acquisition, and the reactivation of HSV increases HIV replication and transmission. New antiviral strategies are required to control resistant viruses and to block HSV spread, thereby reducing HIV acquisition and transmission. These aims will be facilitated through understanding how HSV is transported down nerves and into skin. In this study, we

  6. Herpes Simplex Virus Type-2 and Human Immunodeficiency Virus ...

    African Journals Online (AJOL)

    Objectives: To estimate the seroprevalence of Herpes Simplex Type 2 (HSV-2) and its association with Human Immunodeficiency Virus type 1 (HIV-1) infections in rural Kilimanjaro Tanzania. Methods: A cross-sectional survey was conducted in Oria village from March to June 2005 involving all individuals aged 15-44 years ...

  7. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis

    Czech Academy of Sciences Publication Activity Database

    Abdelmagid, N.; Bereczky-Veress, B.; Atanur, S.; Musilová, Alena; Zídek, Václav; Saba, L.; Warnecke, A.; Khademi, M.; Studahl, M.; Aurelius, E.; Hjalmarsson, A.; Garcia-Dias, A.; Denis, C. V.; Bergström, T.; Sköldenberg, B.; Kockum, I.; Aitman, T.; Hübner, N.; Olsson, T.; Pravenec, Michal; Diez, M.

    2016-01-01

    Roč. 11, č. 5 (2016), e0155832 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) 7E10067; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : Von Willebrand Factor gene * Herpes simplex encephalitis * rat * humans Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

  8. African traditional medication and keloid formation in herpes zoster ...

    African Journals Online (AJOL)

    seen in burn injury, lacerations abrasions and surgery.[7]. Not much had been reported about keloid scar in patients with HZO among indigenous Nigerians despite the fact that dark-skinned individuals are more susceptible to keloid formation. We report a case in which the initial herpes zoster cicatricial changes became ...

  9. On the Mutation Rate of Herpes Simplex Virus Type 1

    OpenAIRE

    Drake, John W.; Hwang, Charles B. C.

    2005-01-01

    All seven DNA-based microbes for which carefully established mutation rates and mutational spectra were previously available displayed a genomic mutation rate in the neighborhood of 0.003 per chromosome replication. The pathogenic mammalian DNA virus herpes simplex type 1 has an estimated genomic mutation rate compatible with that value.

  10. Monoclonal antibodies to Herpes Simplex Virus Type 2

    International Nuclear Information System (INIS)

    McLean-Pieper, C.S.

    1982-01-01

    In this thesis the production and characterisation of monoclonal antibodies to Herpes Simplex Virus Type 2 is described. The development of a suitable radioimmunoassay for the detection of anti-HSV-2 antibodies, and the selection of an optimal immunisation schedule, is given. Three assay systems are described and their reliability and sensitivity compared. (Auth.)

  11. Herpes simplex encephalitis | Ladapo | Nigerian Journal of Clinical ...

    African Journals Online (AJOL)

    Nigerian Journal of Clinical Practice. Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 14, No 1 (2011) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Herpes simplex encephalitis. TA Ladapo, E Oyenusi, FEA Lesi ...

  12. Serological profiles of Herpes simplex virus type 2 among HIV ...

    African Journals Online (AJOL)

    Herpes simplex virus type-2 (HSV-2) is the major cause of genital ulcer diseases (GUD) consequently a significant factor for the acquisition and transmission of human immunodeficiency virus (HIV). Despite its importance there is paucity of data regarding the magnitude of HSV-2 in non-HIV infected population in ...

  13. Herpes Zoster‑Induced Acute Urinary Retention: Two Cases and ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... She was diagnosed as a case of herpes zoster reactivation and treatment commenced with oral methylcobalamin, acyclovir (dosage unknown), and catheterization for 3 days. Despite this, her pain persisted and there was progressive worsening of urinary stream after removal of urinary catheter.

  14. Determination of human herpes simplex virus in clear cerebrospinal ...

    African Journals Online (AJOL)

    The purpose of this study was to test CSF obtained from different regions of Rwanda for herpes simplex viruses (HSV) type 1 and 2 using a commercial multiplex PCR kit. CSF samples were obtained from patients with clinical suspicion of meningitis and encephalitis which may be caused by different microorganisms ...

  15. Breakthrough VZV infection after immunization, presenting as herpes zoster.

    NARCIS (Netherlands)

    Schade, R.P.; Bakkers, J.; Cornelissen, M.; Koster-Kamphuis, L.; Melchers, W.J.G.; Galama, J.M.D.

    2008-01-01

    An immunocompromized, VZV-vaccinated child had a breakthrough infection with VZV, acquired at a day-care centre during a chickenpox outbreak. Interestingly, the infection manifested as herpes zoster of 1 dermatome. Typing showed wild-type virus, which suggests that exogenous reinfection with a new

  16. Herpes zoster in psoriasis patients treated with tofacitinib

    DEFF Research Database (Denmark)

    Winthrop, Kevin L; Lebwohl, Mark; Cohen, Arnon D

    2017-01-01

    BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor. Immunomodulatory therapies can increase the risk for herpes zoster (HZ) in patients with psoriasis. OBJECTIVE: To evaluate the relationship between tofacitinib use and HZ risk. METHODS: We used phases 2 and 3 and long-term extension...

  17. Herpes zoster ophthalmicus in a healthy Nigerian child | Oladigbolu ...

    African Journals Online (AJOL)

    Herpes zoster ophthalmicus (HZO) is rare in children especially those who are immunocompetent. We reported a case of HZO in a healthy 3- year-old girl with no history of exposure or underlying immune-compromising systemic disease. She developed severe ocular complications after treatment. Both parents were non ...

  18. Keratitis in association with herpes zoster and varicella vaccines.

    Science.gov (United States)

    Grillo, A P; Fraunfelder, F W

    2017-07-01

    The objective of this review was to collect reports of keratitis in association with herpes zoster virus (HZV) or varicella zoster virus (VZV) vaccines. HZV vaccination is intended for at-risk adult populations and VZV vaccination is intended for all pediatric patients. We reviewed the literature and reports of keratitis in association with herpes zoster or varicella vaccine from the National Registry of Drug-Induced Ocular Side Effects and the World Health Organization. Twenty-four cases of unilateral keratitis in association with VZV vaccines were collected from the adverse reaction databases and literature. In most cases, the onset of keratitis occurred within days of vaccination and resolved with topical steroid eye drops and oral acyclovir. Data suggest that keratitis in association with herpes zoster or varicella vaccine is rare, is usually self-limited or resolves with treatment. The mechanism may be the persistence of viral antigens in the cornea after VZV vaccination or herpes zoster ophthalmicus. This reaction is probable, given the plausible biological mechanism, the temporal relationship between vaccination and keratitis, and overall patterns of presentation after vaccination. Copyright 2017 Clarivate Analytics.

  19. Obstetric outcomes of human Herpes virus‑2 infection among ...

    African Journals Online (AJOL)

    Objective: This study investigated the obstetric outcomes of herpes simplex virus (HSV‑2) infection among pregnant women. Materials and Methods: In this prospective cohort study, a total of 674 consenting pregnant women attending ante‑natal clinic in the University of Benin Teaching Hospital and Central Hospital Benin ...

  20. CASE REPORT - Maxillary Herpes Zoster with Corneal Involvement ...

    African Journals Online (AJOL)

    Corneal involvement in maxillary herpes zoster is very rare. This report presents the case of a 32 years old 7 months pregnant para2+1 female, who presented with vesiculopapular rashes with hyperpigmented crusts over the maxillary area of the face on the left side with periocular oedema, conjunctivitis and mild punctate ...

  1. SEROPREVALENCE OF HUMAN HERPES VIRUS 8 (HHV8 ...

    African Journals Online (AJOL)

    Praise

    SEROPREVALENCE OF HUMAN HERPES VIRUS 8 (HHV8) INFECTION. AMONG COMMERCIAL SEX WORKERS IN JOS. Zakari1, H., Nimzing2, L., Agabi1, Y. A., Amagam3, P. and Dashen,1 M. M.. 1Department of Microbiology, Faculty of Natural Sciences, University o f Jos, Nigeria. 2Department of Medical Microbiology, ...

  2. Prodromal herpes zoster mimicking odontalgia – A diagnostic ...

    African Journals Online (AJOL)

    During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be properly established before final treatment. Here we present a case of herpes zoster involving the second ...

  3. Polymerase chain reaction to search for Herpes viruses in uveitic ...

    African Journals Online (AJOL)

    Polymerase chain reaction to search for Herpes viruses in uveitic and healthy eyes: a South African perspective. Debbie Laaks1, Derrick P Smit1, Justin Harvey2. 1. Division of Ophthalmology, Department of Surgical Sciences, Faculty of Health Sciences,. University of Stellenbosch, South Africa. 2. Center for Statistical ...

  4. Balance between herpes viruses and immunosuppression after lung transplantation

    NARCIS (Netherlands)

    Verschuuren, Erik Alfons Maria

    2006-01-01

    This thesis focuses on the interplay between two Herpes Virus infections and the immunosuppression used after solid organ (and especially lung) transplantation. It starts with the description of diagnostic tools of Cytomegalovirus (CMV) and their therapeutic implications. Then it addresses the major

  5. Polymerase chain reaction for detection of herpes simplex virus encephalitis.

    Science.gov (United States)

    Aslanzadeh, J; Skiest, D J

    1994-06-01

    A patient with herpes simplex virus encephalitis is described. The polymerase chain reaction (PCR) was used to confirm the diagnosis in cerebrospinal fluid. PCR allows the rapid diagnosis of many infectious organisms, such as HSV, in which prompt diagnosis is essential.

  6. Polymerase chain reaction for detection of herpes simplex virus encephalitis.

    OpenAIRE

    Aslanzadeh, J; Skiest, D J

    1994-01-01

    A patient with herpes simplex virus encephalitis is described. The polymerase chain reaction (PCR) was used to confirm the diagnosis in cerebrospinal fluid. PCR allows the rapid diagnosis of many infectious organisms, such as HSV, in which prompt diagnosis is essential.

  7. Prevalence of Herpes Simplex Virus Antibodies in Dental Students.

    Science.gov (United States)

    Rodu, Brad; And Others

    1992-01-01

    A study of 125 sophomore preclinical dental students found that these young professionals, because of having a low prevalence of herpes simplex virus (HSV) antibodies, are at risk for acquiring a primary HSV infection when treating HSV positive patients and should take precautions to avoid virus transmission. (MSE)

  8. Herpes Simplex Virus Infections of the Central Nervous System.

    Science.gov (United States)

    Whitley, Richard J

    2015-12-01

    This article summarizes knowledge of herpes simplex virus (HSV) infections of the central nervous system (CNS). Disease pathogenesis, detection of DNA polymerase chain reaction (PCR) for diagnosis and prognosis, and approaches to therapy warrant consideration. HSV infection of the CNS is one of few treatable viral diseases. Clinical trials indicate that outcome following neonatal herpes simplex virus type 2 (HSV-2) infections of the CNS is significantly improved when 6 months of suppressive oral acyclovir therapy follows IV antiviral therapy. In contrast, herpes simplex virus type 1 (HSV-1) infections of the brain do not benefit from extended oral antiviral therapy. This implies a difference in disease pathogenesis between HSV-2 and HSV-1 infections of the brain. PCR detection of viral DNA in the CSF is the gold standard for diagnosis. Use of PCR is now being adopted as a basis for determining the duration of therapy in the newborn. HSV infections are among the most common encountered by humans; seropositivity occurs in 50% to 90% of adult populations. Herpes simplex encephalitis, however, is an uncommon result of this infection. Since no new antiviral drugs have been introduced in nearly 3 decades, much effort has focused on learning how to better use acyclovir and how to use existing databases to establish earlier diagnosis.

  9. Herpes zoster myelitis: report of two cases | Amanyo | East African ...

    African Journals Online (AJOL)

    Investigation including imaging of the spinal cord did not reveal any other cause of the neurological deficit. The two responded very well to treatment with acyclovir. Herpes zoster myelitis is a condition likely to rise with the upsurge of HIV infection and there is a need to identify the condition early. We also review the literature ...

  10. Computed tomography in young children with herpes simplex virus encephalitis

    International Nuclear Information System (INIS)

    Sugimoto, T.; Woo, M.; Okazaki, H.; Nishida, N.; Hara, T.; Yasuhara, A.; Kasahara, M.; Kobayashi, Y.

    1985-01-01

    Computed tomographic (CT) scans were obtained from eight infants and young children with herpes simplex virus encephalitis. In two cases the initial scan showed diffuse edematous changes as a mass effect without laterality. Unilateral localized low attenuation in the initial scan was evident 4 days after the onset in one patient, and high attenuation in the initial scan appeared on the 6th day in another patient, but in general, it was not possible to establish an early diagnosis of herpes simplex virus encephalitis from CT scan. In the longitudinal study the calcification with ventriculomegaly appeared in 3 of 5 survivors, and gyriform calcification in 2 of 3 patients, respectively. The appearance of multicystic encephalomalacia was evident in one patient 6 months after the onset of neonatal herpes simplex encephalitis. It is shown that the CT findings of neonates and young children with herpes simplex encephalitis are different from those of older children and adults, and the importance of longitudinal CT studies was stressed in clarifying the pathophysiology of the central nervous system involvement in survivors. (orig.)

  11. Obstetric outcomes of human Herpes virus‑2 infection among ...

    African Journals Online (AJOL)

    2014-09-23

    Sep 23, 2014 ... Objective: This study investigated the obstetric outcomes of herpes simplex virus (HSV‑2) infection among pregnant women. Materials and Methods: In this prospective cohort study, a total of 674 consenting pregnant women attending ante‑natal clinic in the University of Benin Teaching Hospital and Central ...

  12. Herpes Zoster‑Induced Acute Urinary Retention: Two Cases and ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... We report two uncommon cases of acute urinary retention in Chinese patients caused by reactivation of sacral herpes zoster and ... creations are licensed under the identical terms. For reprints contact: reprints@medknow.com .... anonymity cannot be guaranteed. Financial support and sponsorship. Nil.

  13. Recurrent herpes simplex virus keratitis in a young Nigerian male ...

    African Journals Online (AJOL)

    A comprehensive case history and slit lamp examination revealed the presence of dendritic ulcer in the left eye of the patient. The patient was diagnosed with recurrent herpes simplex virus keratitis. An aggressive multi-treatment plan involving the use of antiviral, antibiotics, and anti inflammatory drugs was administered to ...

  14. Sequencing and phylogenetic analysis of Herpes simplex virus type ...

    African Journals Online (AJOL)

    momtaz

    2012-01-19

    Jan 19, 2012 ... Herpes simplex virus type 2 (HSV-2) is the main cause of recurrent genital infection (Slomka, 1996). Most infections are asymptomatic. The virus establishes latent infection in the local ganglia and is reactivated and shed frequently. Antibodies to HSV infections become detectable in serum samples (Koelle ...

  15. Recombinant renewable polyclonal antibodies.

    Science.gov (United States)

    Ferrara, Fortunato; D'Angelo, Sara; Gaiotto, Tiziano; Naranjo, Leslie; Tian, Hongzhao; Gräslund, Susanne; Dobrovetsky, Elena; Hraber, Peter; Lund-Johansen, Fridtjof; Saragozza, Silvia; Sblattero, Daniele; Kiss, Csaba; Bradbury, Andrew R M

    2015-01-01

    Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products.

  16. A Dominant Mutation in Human RAD51 Reveals Its Function in DNA Interstrand Crosslink Repair Independent of Homologous Recombination.

    Science.gov (United States)

    Wang, Anderson T; Kim, Taeho; Wagner, John E; Conti, Brooke A; Lach, Francis P; Huang, Athena L; Molina, Henrik; Sanborn, Erica M; Zierhut, Heather; Cornes, Belinda K; Abhyankar, Avinash; Sougnez, Carrie; Gabriel, Stacey B; Auerbach, Arleen D; Kowalczykowski, Stephen C; Smogorzewska, Agata

    2015-08-06

    Repair of DNA interstrand crosslinks requires action of multiple DNA repair pathways, including homologous recombination. Here, we report a de novo heterozygous T131P mutation in RAD51/FANCR, the key recombinase essential for homologous recombination, in a patient with Fanconi anemia-like phenotype. In vitro, RAD51-T131P displays DNA-independent ATPase activity, no DNA pairing capacity, and a co-dominant-negative effect on RAD51 recombinase function. However, the patient cells are homologous recombination proficient due to the low ratio of mutant to wild-type RAD51 in cells. Instead, patient cells are sensitive to crosslinking agents and display hyperphosphorylation of Replication Protein A due to increased activity of DNA2 and WRN at the DNA interstrand crosslinks. Thus, proper RAD51 function is important during DNA interstrand crosslink repair outside of homologous recombination. Our study provides a molecular basis for how RAD51 and its associated factors may operate in a homologous recombination-independent manner to maintain genomic integrity. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage

    DEFF Research Database (Denmark)

    Mankouri, Hocine W; Hickson, Ian D

    2006-01-01

    Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth, hyperrecombination, and a failure to fully activate DNA damage checkpoints in S phase. Here, we report that overexpression of a dominant-negative allele of TOP3, TOP3(Y356F), which lacks the catalytic (decatenation) activity of Top3......, the catalytic activity of Top3 is not required for DNA damage checkpoint activation, but it is required for normal S-phase progression after DNA damage. We also present evidence that the checkpoint-mediated cell cycle delay and persistence of X-shaped DNA molecules resulting from overexpression of TOP3(Y356F......) are downstream of Rad51 function. We propose that Top3 functions in S phase to both process homologous recombination intermediates and modulate checkpoint activity....

  18. Functional Hierarchy of Herpes Simplex Virus 1 Viral Glycoproteins in Cytoplasmic Virion Envelopment and Egress

    Science.gov (United States)

    Chouljenko, Dmitry V.; Kim, In-Joong; Chouljenko, Vladimir N.; Subramanian, Ramesh; Walker, Jason D.

    2012-01-01

    Herpes simplex virus 1 (HSV-1) viral glycoproteins gD (carboxyl terminus), gE, gK, and gM, the membrane protein UL20, and membrane-associated protein UL11 play important roles in cytoplasmic virion envelopment and egress from infected cells. We showed previously that a recombinant virus carrying a deletion of the carboxyl-terminal 29 amino acids of gD (gDΔct) and the entire gE gene (ΔgE) did not exhibit substantial defects in cytoplasmic virion envelopment and egress (H. C. Lee et al., J. Virol. 83:6115–6124, 2009). The recombinant virus ΔgM2, engineered not to express gM, produced a 3- to 4-fold decrease in viral titers and a 50% reduction in average plaque sizes in comparison to the HSV-1(F) parental virus. The recombinant virus containing all three mutations, gDΔct-ΔgM2-ΔgE, replicated approximately 1 log unit less efficiently than the HSV-1(F) parental virus and produced viral plaques which were on average one-third the size of those of HSV-1(F). The recombinant virus ΔUL11-ΔgM2, engineered not to express either UL11 or gM, replicated more than 1 log unit less efficiently and produced significantly smaller plaques than UL11-null or gM-null viruses alone, in agreement with the results of Leege et al. (T. Leege et al., J. Virol. 83:896-907, 2009). Analyses of particle-to-PFU ratios, relative plaque size, and kinetics of virus growth and ultrastructural visualization of glycoprotein-deficient mutant and wild-type virions indicate that gDΔct, gE, and gM function in a cooperative but not redundant manner in infectious virion morphogenesis. Overall, comparisons of single, double, and triple mutant viruses generated in the same HSV-1(F) genetic background indicated that lack of either UL20 or gK expression caused the most severe defects in cytoplasmic envelopment, egress, and infectious virus production, followed by the double deletion of UL11 and gM. PMID:22318149

  19. The Diagnosis of Genital Herpes – Beyond Culture: An Evidence-Based Guide for the Utilization of Polymerase Chain Reaction and Herpes Simplex Virus Type-Specific Serology

    Directory of Open Access Journals (Sweden)

    S Ratnam

    2007-01-01

    Full Text Available Accurate identification of persons with genital herpes is necessary for optimal patient management and prevention of transmission. Because of inherent inaccuracies, clinical diagnosis of genital herpes should be confirmed by laboratory testing for the causative agents herpes simplex virus type 1 (HSV-1 and HSV type 2 (HSV-2. Further identification of the HSV type is valuable for counselling on the natural history of infection and risk of transmission. Laboratory methods include antigen detection, culture, polymerase chain reaction (PCR and conventional and type-specific serology (TSS. PCR has, by far, the greater sensitivity and should be the test of choice for symptomatic cases. HSV-2 TSS is indicated for patients with genital lesions in whom antigen detection, culture or PCR fail to detect HSV, and for patients who are asymptomatic but have a history suggestive of genital herpes. HSV-2 TSS is further indicated for patients infected with HIV. HSV-2 TSS along with HSV-1 TSS may be considered, as appropriate, in evaluating infection and/or immune status in couples discordant for genital herpes, women who develop their first clinical episode of genital herpes during pregnancy, asymptomatic pregnant women whose partners have a history of genital herpes or HIV infection, and women contemplating pregnancy or considering sexual partnership with those with a history of genital herpes. The above should be performed in conjunction with counselling of infected persons and their sex partners.

  20. Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations

    Directory of Open Access Journals (Sweden)

    Leary Jeffry J

    2002-05-01

    Full Text Available Abstract Background The thymidine kinase (tk mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to HSV-1. Methods A panel of HSV-1 and HSV-2, along with polymerase-recombinant viruses expressing type 2 polymerase (Pol within a type 1 genome, were evaluated using the tk and non-HSV DNA mutagenesis assays to measure HSV replication-dependent errors and determine whether the higher mutation frequency of HSV-2 is a distinct property of type 2 polymerases. Results Although HSV-2 have mutation frequencies higher than HSV-1 in the tk assay, these errors are assay-specific. In fact, wild type HSV-1 and the antimutator HSV-1 PAAr5 exhibited a 2–4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Furthermore, regardless of assay, HSV-1 recombinants expressing HSV-2 Pol had error rates similar to HSV-1, whereas the high mutator virus, HSV-2 6757, consistently showed signficant errors. Additionally, plasmid DNA containing the HSV-2 tk gene, but not type 1 tk or LacZ DNA, was shown to form an anisomorphic DNA stucture. Conclusions This study suggests that the Pol is not solely responsible for the virus-type specific differences in mutation frequency. Accordingly, it is possible that (a mutations may be modulated by other viral polypeptides cooperating with Pol, and (b the localized secondary structure of the viral genome may partially account for the apparently enhanced error frequency of HSV-2.

  1. Isolation and Characterization of the Herpes Simplex Virus 1 Terminase Complex

    Science.gov (United States)

    Heming, Jason D.; Huffman, Jamie B.; Jones, Lisa M.

    2014-01-01

    During herpes simplex virus 1 (HSV-1) infection, empty procapsids are assembled and subsequently filled with the viral genome by means of a protein complex called the terminase, which is comprised of the HSV-1 UL15, UL28, and UL33 proteins. Biochemical studies of the terminase proteins have been hampered by the inability to purify the intact terminase complex. In this study, terminase complexes were isolated by tandem-affinity purification (TAP) using recombinant viruses expressing either a full-length NTAP-UL28 fusion protein (vFH476) or a C-terminally truncated NTAP-UL28 fusion protein (vFH499). TAP of the UL28 protein from vFH476-infected cells, followed by silver staining, Western blotting, and mass spectrometry, identified the UL15, UL28, and UL33 subunits, while TAP of vFH499-infected cells confirmed previous findings that the C terminus of UL28 is required for UL28 interaction with UL33 and UL15. Analysis of the oligomeric state of the purified complexes by sucrose density gradient ultracentrifugation revealed that the three proteins formed a complex with a molecular mass that is consistent with the formation of a UL15-UL28-UL33 heterotrimer. In order to assess the importance of conserved regions of the UL15 and UL28 proteins, recombinant NTAP-UL28 viruses with mutations of the putative UL28 metal-binding domain or within the UL15 nuclease domain were generated. TAP of UL28 complexes from cells infected with each domain mutant demonstrated that the conserved cysteine residues of the putative UL28 metal-binding domain and conserved amino acids within the UL15 nuclease domain are required for the cleavage and packaging functions of the viral terminase, but not for terminase complex assembly. PMID:24155374

  2. Involvement of UL24 in herpes-simplex-virus-1-induced dispersal of nucleolin

    International Nuclear Information System (INIS)

    Lymberopoulos, Maria H.; Pearson, Angela

    2007-01-01

    UL24 of herpes simplex virus 1 is important for efficient viral replication, but its function is unknown. We generated a recombinant virus, vHA-UL24, encoding UL24 with an N-terminal hemagglutinin tag. By indirect immunofluorescence at 9 h post-infection (hpi), we detected HA-UL24 in nuclear foci and in cytoplasmic speckles. HA-UL24 partially co-localized with nucleolin, but not with ICP8 or coilin, markers for nucleoli, viral replication compartments, and Cajal bodies respectively. HA-UL24 staining was often juxtaposed to that of another nucleolar protein, fibrillarin. Analysis of HSV-1-induced nucleolar modifications revealed that by 18 hpi, nucleolin staining had dispersed, and fibrillarin staining went from clusters of small spots to a few separate but prominent spots. Fibrillarin redistribution appeared to be independent of UL24. In contrast, cells infected with a UL24-deficient virus retained foci of nucleolin staining. Our results demonstrate involvement of UL24 in dispersal of nucleolin during infection

  3. Antiviral resistance in herpes simplex virus and varicella-zoster virus infections: diagnosis and management.

    Science.gov (United States)

    Piret, Jocelyne; Boivin, Guy

    2016-12-01

    Aciclovir (ACV) is the first-line drug for the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Long-term administration of ACV for the treatment of severe infections in immunocompromised patients can lead to the development of drug resistance. Furthermore, the emergence of isolates resistant to ACV is increasingly recognized in immunocompetent individuals with herpetic keratitis. This review describes the mechanisms involved in drug resistance for HSV and VZV, the laboratory diagnosis and management of patients with infections refractory to ACV therapy. Genotypic testing is more frequently performed for the diagnosis of infections caused by drug-resistant HSV or VZV isolates. Molecular biology-based systems for the generation of recombinant viruses have been developed to link unknown mutations with their drug phenotypes. Fast and sensitive methods based on next-generation sequencing will improve the detection of heterogeneous viral populations of drug-resistant viruses and their temporal changes during antiviral therapy, which could allow better patient management. Novel promising compounds acting on targets that differ from the viral DNA polymerase are under clinical development. Antiviral drug resistance monitoring for HSV and VZV is required for a rational use of antiviral therapy in high-risk populations.

  4. Site directed recombination

    Science.gov (United States)

    Jurka, Jerzy W.

    1997-01-01

    Enhanced homologous recombination is obtained by employing a consensus sequence which has been found to be associated with integration of repeat sequences, such as Alu and ID. The consensus sequence or sequence having a single transition mutation determines one site of a double break which allows for high efficiency of integration at the site. By introducing single or double stranded DNA having the consensus sequence flanking region joined to a sequence of interest, one can reproducibly direct integration of the sequence of interest at one or a limited number of sites. In this way, specific sites can be identified and homologous recombination achieved at the site by employing a second flanking sequence associated with a sequence proximal to the 3'-nick.

  5. Nonradiative recombination in semiconductors

    CERN Document Server

    Abakumov, VN; Yassievich, IN

    1991-01-01

    In recent years, great progress has been made in the understandingof recombination processes controlling the number of excessfree carriers in semiconductors under nonequilibrium conditions. As a result, it is now possible to give a comprehensivetheoretical description of these processes. The authors haveselected a number of experimental results which elucidate theunderlying physical problems and enable a test of theoreticalmodels. The following topics are dealt with: phenomenological theory ofrecombination, theoretical models of shallow and deep localizedstates, cascade model of carrier captu

  6. Herpes zoster – available epidemiological data in Slovenia

    Directory of Open Access Journals (Sweden)

    Maja Sočan

    2006-09-01

    Full Text Available Background: Herpes zoster results from reactivation of latent varicella zoster virus (VZV in dorsal nerve ganglia. Herpes zoster is characterized by a painful dermatomal vesicular rash. Reactivation results from impaired cell-mediated immunity. The determinants of reactivation in individuals with no underlying immunosuppression are poorly understood. The introduction of vaccination against varicella is expected to lower the incidence rate of chicken pox. The influence of vaccination on herpes zoster morbidity is not clear and demands enhanced surveillance. Before the introduction of vaccination, the available epidemiological data should be analyzed for the availability, value and shortcomings.Methods: The data from two electronic data-sets of Institute of Public Health of the Republic Slovenia were analysed: notified cases and number of consultations on primary level for herpes zoster – »ZUBSTAT« (data set of all first visits in primary care, Institute of Public Health of the Republic Slovenia. The data were stratified by age and sex. The hospitalization data were extracted from Eletronic data set for diseases which require hospitalization (entitled BOLOB, IPH. For notified and hospitalized cases also the month when shigles appeared was available.Results: The number of notified cases increased steadily from year 1995 when mandatory reporting has been implemented. In year 2005 the incidence rate rose to 74/100,000. Approximately a quarter of cases (23.4 % was 70 years of age or older. According to the second data-set, which encompasses first visits in primary care, 5891 to 6527 patients were coded as herpes zoster. The incidence rate increases with age, being highest after age of 65 years (675 to 760/100,000. Women have higher incidence rate of herpes zoster in almost all age groups. The distribution of notified cases suggests seasonal peak in summer. The highest number of admissions was in September and October.Conclusions: The number of

  7. Pharmacology of Recombinant Adeno-associated Virus Production

    Directory of Open Access Journals (Sweden)

    Magalie Penaud-Budloo

    2018-03-01

    Full Text Available Recombinant adeno-associated viral (rAAV vectors have been used in more than 150 clinical trials with a good safety profile and significant clinical benefit in many genetic diseases. In addition, due to their ability to infect non-dividing and dividing cells and to serve as efficient substrate for homologous recombination, rAAVs are being used as a tool for gene-editing approaches. However, manufacturing of these vectors at high quantities and fulfilling current good manufacturing practices (GMP is still a challenge, and several technological platforms are competing for this niche. Herein, we will describe the most commonly used upstream methods to produce rAAVs, paying particular attention to the starting materials (input used in each platform and which related impurities can be expected in final products (output. The most commonly found impurities in rAAV stocks include defective particles (i.e., AAV capsids that do contain the therapeutic gene or are not infectious, residual proteins from host cells and helper viruses (adenovirus, herpes simplex virus, or baculoviruses, and illegitimate DNA from plasmids, cells, or helper viruses that may be encapsidated into rAAV particles. Given the role that impurities may play in immunotoxicity, this article reviews the impurities inherently associated with each manufacturing platform.

  8. Clinical profile of Herpes zoster in a rural tertiary care hospital in South India

    OpenAIRE

    Chankramat Sujatha Vinod; Hariharasubramony Ambika; Raghunath Nithya; Jayaprasad Sushmitha

    2014-01-01

    Introduction: Herpes zoster (Hz), which presents as localized, painful cutaneous eruption is a common clinical problem, particularly among adults of above 50 years of age and immunocompromised patients. It results from reactivation of varicella zoster virus. Aim: To analyze the clinical pattern of herpes zoster with special emphasis to the precipitating factors and incidence of post herpetic neuralgia. Material and Methods: 100 clinically diagnosed cases of herpes zoster, attending ...

  9. Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

    DEFF Research Database (Denmark)

    Christensen, Tove

    2005-01-01

    may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation...... and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS. Copyright (c) 2005 ...

  10. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

    International Nuclear Information System (INIS)

    Vafai, A.; Wellish, M.; Devlin, M.; Gilden, D.H.; Murray, R.S.

    1988-01-01

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia

  11. Herpes Zoster Ophthalmicus With Sixth Cranial Nerve Palsy: A Case Report

    Directory of Open Access Journals (Sweden)

    Kemal Balcı

    2008-10-01

    Full Text Available Scientific BACKGROUND: Herpes zoster ophthalmicus represents aproximately 25% of all zoster infections. However extraocular gaze palsy in association with herpes zoster infection is extremely rare. OBJECTIVE: We presented here a patient who had herpes zoster ophthalmicus with sixth cranial nerve palsy. CASE: The sixty year old patient had suffered from left retroorbital pain, conjunctival congestion and rashes on the left forehead and the nose and developed ipsilateral sixth cranial nerve palsy. RESULT: Herpes zoster virus infection should be taken into consideration in patients with extraocular paralysis and early treatment may prevent such complications

  12. Apparent rarity of asymptomatic herpes cervicitis in a woman with intra-uterine contraceptive device

    Directory of Open Access Journals (Sweden)

    Adeola Fowotade

    2013-12-01

    Full Text Available Infection with genital herpes simplex virus (HSV remains a common viral sexually transmitted disease, often subclinical and a major worldwide problem of women of reproductive age group. Herpes cervicitis is an unusual presentation of Herpes simplex virus infection in females. The finding of herpes cervicitis on routine pap smear of an asymptomatic woman on Intrauterine contraceptive device still further supports the need for increased awareness on the possibility of Herpes simplex virus infection among women, particularly those on Intrauterine contraceptive device. The index case is a 28 years old Nigerian female who was referred to our Special Treatment Clinic on account of an abnormal pap smear cytology which was in keeping with Herpes cervicitis. There was no history of genital ulcer in this patient; however ELISA for HSV 2 IgM was positive in her. We therefore describe a case of herpes cervicitis in an asymptomatic woman on intrauterine contraceptive device. This case highlights to clinicians the need to be aware of the possibility of this association and to carry out relevant investigations so as to identify and treat these patients appropriately. Therefore, there is a need to put in place adequate public health intervention strategy to prevent genital herpes in women of reproductive age group with a view to preventing the possibility of congenital herpes in subsequent pregnancy.

  13. Combined Therapy at Persistent Herpes Virus Infection in Sickly Children

    Directory of Open Access Journals (Sweden)

    F. S. Kharlamova

    2012-01-01

    Full Text Available We examined 40 sickly children with recurrent croup (RC — 28 and bronchial obstruction (ROB — 8, (RC + ROB — 4 aged from 18 months till 14 years. We found that high frequency of persistent herpes viruses usually occurs as associations with CMV, EBV and human herpes virus 6 type. We substantiated anti viral and immune corrective therapy in two schemes compared in efficacy: the 1st group was administered monotherapy with Viferon, and the 2nd group received combined therapy Viferon + Arbidol in doses according to the age during three months. We received a more expressed clinical immunologic effect from the therapy with decreased antigenic load and frequency of recurrence of RC and ROB with Viferon application in suppositories in combination with Arbidol per orally in the intermittent scheme during three months. 

  14. Evolution of rational vaccine designs for genital herpes immunotherapy.

    Science.gov (United States)

    Kaufmann, Johanna Katharina; Flechtner, Jessica Baker

    2016-04-01

    Immunotherapeutic vaccines have emerged as a novel treatment modality for genital herpes, a sexually transmitted disease mainly caused by herpes simplex virus type 2. The approaches to identify potential vaccine antigens have evolved from classic virus attenuation and characterization of antibody and T cell responses in exposed, but seronegative individuals, to systematic screens for novel T cell antigens. Combined with implementation of novel vaccine concepts revolving around immune evasion and local recruitment of immune effectors, the development of a safe and effective therapeutic vaccine is within reach. Here, we describe the vaccine approaches that currently show promise at clinical and pre-clinical stages and link them to the evolving scientific strategies that led to their identification. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Associations between individual and relationship characteristics and genital herpes disclosure.

    Science.gov (United States)

    Myers, Jaime L; Buhi, Eric R; Marhefka, Stephanie; Daley, Ellen; Dedrick, Robert

    2016-10-01

    Disclosure is often a challenge for individuals living with genital herpes. This study explores determinants of genital herpes disclosure with one's most recent sexual partner using an online questionnaire (n = 93). The majority of participants reported (80.4%) disclosure. Among non-disclosers, fear of negative partner reactions was the primary reason for non-disclosure. Age, relationship commitment, time in relationship, and expectations of partner's reaction were statistically significant predictors at the bivariate level. Reaction expectations and relationship commitment remained significant in the multivariate logistic regression model. Findings indicate that future disclosure research should focus on relationship context and managing negative expectations to increase disclosure. © The Author(s) 2015.

  16. Acute and recurrent herpes simplex in several strains of mice.

    Science.gov (United States)

    Harbour, D A; Hill, T J; Blyth, W A

    1981-07-01

    Acute and recurrent herpes simplex was studied after infection in the ear of two outbred and five inbred strains of mice. In all strains tested there was clinical evidence of infection, and a proportion of the mice became latently infected in the cervical ganglia. Six weeks after infection, when attempts were made to induce recurrent desease by stripping the ears of the mice with cellophange tape, a proportion of animals of each strain developed recurrent disease, characterized by erythema in the skin. At monthly intervals thereafter, the ears were stripped again and, on each occasion, a proportion of the animals developed recurrent disease, with the exception of Balb/c mice. The different reaction of Balb/c and other inbred strains might prove useful in studies on the mechanism of control of recurrent herpes simplex.

  17. Herpes zoster in multiple myeloma patients during bortezomib treatment

    Directory of Open Access Journals (Sweden)

    I. N. Nazarova

    2011-01-01

    Full Text Available Recent advances in multiple myeloma (MM treatment associated with new drug use including bortezomib. Experiences in wide ambul atory drug use confirm therapy success for this serious disease, but at the same time reveals the most common side effects. One of th e most significant is the reactivation of Herpes zoster , which leads to decrease MM therapy results because of inability to perform standard therapy in these patients. Literature data and own experiences about reactivation of Herpes zoster during bortezomib therapy as monothe rapy and in combination, which varies from 7 to 34% according to different authors and 25% of own experiences, is presented. Treatment and preventive schedule of this complication are shown.

  18. Superior orbital fissure syndrome in herpes zoster ophthalmicus.

    LENUS (Irish Health Repository)

    Kirwan, R P

    2012-02-01

    AIM: To report a case of superior orbital fissure syndrome (SOFS) in a patient with herpes zoster ophthalmicus (HZO). MATERIALS AND METHODS: A case report. RESULTS: A 71-year-old male with HZO presented acutely to accident and emergency complaining of right vision loss, double vision and drowsiness. The right visual acuity was counting fingers. There was no relative afferent pupillary defect. He had interstitial keratitis, ptosis, proptosis and total ophthalmoplaegia. The signs indicated HZO complicated by SOFS. Brain imaging and lumbar puncture confirmed the diagnosis of varicella zoster encephalitis. Systemic acyclovir and prednisolone led to recovery of visual acuity and ocular motility in addition to resolution of his proptosis and ptosis. CONCLUSION: SOFS is a rare complication of herpes zoster infection. With the appropriate treatment and follow-up, patients may be reassured that recovery of their visual acuity and ocular motility will occur.

  19. Herpes Simplex Encephalitis Presenting with Normal CSF Analysis

    International Nuclear Information System (INIS)

    Ahmed, R.; Kiani, I. G.; Shah, F.; Rehman, R. N.; Haq, M. E.

    2013-01-01

    A 28 years old female presented with headache, fever, altered sensorium and right side weakness for one week. She was febrile and drowsy with right sided hemiplegia and papilledema. Tuberculous or bacterial meningitis, tuberculoma and abscess were at the top of the diagnosis list followed by Herpes simplex meningo-encephalitis (HSE). MRI showed abnormal signal intensity of left temporal lobe without significant post-contrast enhancement and midline shift. CSF examination was normal, gram stain and Ziehl-Neelsen stain showed no micro-organism, or acid fast bacilli. CSF for MTB PCR was negative. PCR DNA for Herpes simplex 1 on CSF was detected. Acyclovir was started and the patient was discharged after full recovery. A high index of suspicion is required for HSE diagnosis in Pakistan where other infections predominantly affect the brain and HSE may be overlooked as a potential diagnosis. (author)

  20. Neonatal herpes simplex virus infection: epidemiology and treatment.

    Science.gov (United States)

    James, Scott H; Kimberlin, David W

    2015-03-01

    Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Treatment of herpes simplex labialis with low power laser therapy.

    OpenAIRE

    Bianka M. González; Adel Hernández; Adonis Estevez

    2009-01-01

    Introducción: El herpes simple es causado por Herpes virus hominis, que produce una afección eruptiva aguda de uno o más grupos de vesículas sobre una base eritematosa; puede localizarse en cualquier parte del cuerpo preferentemente en la boca y los genitales precedida y acompañada de ardor y prurito. Objetivos: Se evaluó la efectividad del tratamiento con láser de baja potencia en relación al tratamiento convencional según la evolución clínica, desaparición de síntomas y signos en los pacien...

  2. Occupational Therapy for a Boy Patient with Herpes Simplex Encephalitis

    OpenAIRE

    豊森, 千史; 佐藤, 陽子

    1993-01-01

    A boy aged three years and two months had been affected with Herpes simplex encephalitis before five months and was referred to our occupational therapeutic division. He showed stranger reaction and separation anxiety. Additonally, he had some developmental disorders in the areas of self-care skills, cognition and communication proficiency. Besides these, he felt little interest in people or things, and had a short attention span. After treatment of occupational therapy for two years and ten ...

  3. Herpes simplex virus bronchiolitis in a cannabis user

    Directory of Open Access Journals (Sweden)

    Daniel H. Libraty

    2014-01-01

    Full Text Available Herpes simplex virus (HSV lower respiratory tract infections in adults are uncommon. We present a case of HSV bronchiolitis and pneumonitis in an immunocompetent individual, likely linked to chronic habitual marijuana use and a herpetic orolabial ulcer. The case serves as a reminder to consider HSV as a potential unusual cause of lower respiratory tract infection/inflammation in individuals with chronic habitual marijuana use.

  4. Orbital apex syndrome associated with herpes zoster ophthalmicus

    Directory of Open Access Journals (Sweden)

    Kurimoto T

    2011-11-01

    Full Text Available Takuji Kurimoto1, Masahiro Tonari1, Norihiko Ishizaki1, Mitsuhiro Monta2, Saori Hirata2, Hidehiro Oku1, Jun Sugasawa1, Tsunehiko Ikeda11Department of Ophthalmology, Osaka Medical College, 2Department of Ophthalmology, Shitennoji Hospital, Osaka, JapanAbstract: We report our findings for a patient with orbital apex syndrome associated with herpes zoster ophthalmicus. Our patient was initially admitted to a neighborhood hospital because of nausea and loss of appetite of 10 days' duration. The day after hospitalization, she developed skin vesicles along the first division of the trigeminal nerve, with severe lid swelling and conjunctival injection. On suspicion of meningoencephalitis caused by varicella zoster virus, antiviral therapy with vidarabine and betamethasone was started. Seventeen days later, complete ptosis and ophthalmoplegia developed in the right eye. The light reflex in the right eye was absent and anisocoria was present, with the right pupil larger than the left. Fat-suppressed enhanced T1-weighted magnetic resonance images showed high intensity areas in the muscle cone, cavernous sinus, and orbital optic nerve sheath. Our patient was diagnosed with orbital apex syndrome, and because of skin vesicles in the first division of the trigeminal nerve, the orbital apex syndrome was considered to be caused by herpes zoster ophthalmicus. After the patient was transferred to our hospital, prednisolone 60 mg and vidarabine antiviral therapy was started, and fever and headaches disappeared five days later. The ophthalmoplegia and optic neuritis, but not the anisocoria, gradually resolved during tapering of oral therapy. From the clinical findings and course, the cause of the orbital apex syndrome was most likely invasion of the orbital apex and cavernous sinus by the herpes virus through the trigeminal nerve ganglia.Keywords: varicella zoster virus, orbital apex syndrome, herpes zoster ophthalmicus, complete ophthalmoplegia

  5. Herpes zoster infection, vaccination and immunocompromised rheumatology patients.

    LENUS (Irish Health Repository)

    O'Connor, Mortimer B

    2013-01-01

    Varicella is a self-limiting and relatively mild disease of childhood, although it is frequently more severe and complicated among the immunocompromised rheumatology patients on immunomodulator therapies. In addition, future reactivation of the dormant virus in dorsal root ganglia may cause herpes zoster infection, which can be very debilitating. In this manuscript, we discuss the nature of this infection along with its potential vaccine especially among rheumatology patients.

  6. Contrast enhancement of the gyri in herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Schumacher, K.A.; Langer, M.; Langer, R.

    1982-01-01

    A case of herpes simplex encephalitis was examined by computer tomography. Both cerebral hemispheres showed contrast enhancement of the gyri. The cause of this is considered. The increased contrast medium accumulation in the affected areas is probably due to the marked vascular proliferation which can be demonstrated anatomically, and to the rapid escape of contrast from the capillaries into the interstitial spaces. The findings of other authors, which differ somewhat, are discussed. (orig.) [de

  7. Eye and Periocular Skin Involvement in Herpes Zoster Infection

    Science.gov (United States)

    Kalogeropoulos, Chris D.; Bassukas, Ioannis D.; Moschos, Marilita M.; Tabbara, Khalid F.

    2015-01-01

    Herpes zoster ophthalmicus (HZO) is a clinical manifestation of the reactivation of latent varicella zoster virus (VZV) infection and is more common in people with diminished cell-mediated immunity. Lesions and pain correspond to the affected dermatomes, mostly in first or second trigeminal branch and progress from maculae, papules to vesicles and form pustules, and crusts. Complications are cutaneous, visceral, neurological, ocular, but the most debilitating is post-herpetic neuralgia. Herpes zoster ophthalmicus may affect all the ophthalmic structures, but most severe eye-threatening complications are panuveitis, acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN) as well. Antiviral medications remain the primary therapy, mainly useful in preventing ocular involvement when begun within 72 hours after the onset of the rash. Timely diagnosis and management of HZO are critical in limiting visual morbidity. Vaccine in adults over 60 was found to be highly effective to boost waning immunity what reduces both the burden of herpes zoster (HZ) disease and the incidence of post-herpetic neuralgia (PHN). PMID:27800502

  8. Bullous Variant of Sweet's Syndrome after Herpes Zoster Virus Infection

    Science.gov (United States)

    Endo, Yuichiro; Tanioka, Miki; Tanizaki, Hideaki; Mori, Minako; Kawabata, Hiroshi; Miyachi, Yoshiki

    2011-01-01

    Aim Cutaneous manifestations of Sweet's syndrome (SS) are typically painful plaque-forming erythematous papules, while bullae are quite uncommon. We present a case of bullous variant of SS in acute myeloid leukaemia. In this case, herpes infection of the left mandible had preceded the development of SS. Case Report A 75-year-old male with myelodysplastic syndrome first presented with herpes zoster virus infection-like bullae and erosive plaques on the left side of the face and neck. Treatment with valacyclovir and antibiotics was effective only for the initial lesions, whereas the other bullae kept developing predominantly on the left side. Histopathological study revealed epidermal bulla formation, pandermal neutrophilic infiltration, erythrocyte extravasation and subepidermal oedema, but no vasculitis. The findings suggested the diagnosis of bullous variant of SS. Discussion Our case was unique in that bullous SS symptoms developed predominantly on one side of the cheek and neck where the herpes zoster infection occurred prior to SS. The tendency may explain the possible association between viral infection and development of SS. PMID:22220147

  9. Epidemiological surveillance of herpes viral encephalitis in Cordoba, Colombia.

    Science.gov (United States)

    Tique, Vaneza; Mattar, Salim; Freire, María; Illian, Eduardo; Camargo, Francisco; Vergara, Oscar; Moraes-Figueiredo, Luiz T

    2016-08-01

    Objective To establish an epidemiological surveillance of viral herpes encephalitis in major hospitals of Monteria, Cordoba. Methods From September 2009 to December 2011, a descriptive study of cases of viral encephalitis was made in three hospitals in the city of Monteria. Cerebrospinal fluid (CSF) samples from 118 patients were included in the study. Clinical aspects, as well as cytochemical and microbiological analysis (Gram stain and culture) of CSF, were used for selecting the patients. Virus detection was performed by using multiplex nested PCR for Herpes simplex virus 1 and 2, Epstein Barr virus, Cytomegalovirus and Varicella zoster virus. Results Viral DNA of herpesvirus was detected in the CSFs of 30 (25.4 %) participants, as follows: 22 (18.6 %) Herpes simplex 1 and 2 viruses, 4 (3.3 %) Cytomegalovirus and 1 (0.8 %) Varicella zoster virus. Co-infections were observed in 3 patients (2.5 %), 1 case by HSV-VZV and 2 cases by CMV/HSV. The clinical manifestations of the patients included: headache (18.6 %), fever (14.4 %), asthenia (10.1 %), seizures (9.3 %), vomiting (8.4 %), and stiff neck (5.9 %). Thirty percent of the patients also had HIV-AIDS. A case fatality rate of 20 % was observed for the patients. Conclusions This paper shows that herpesvirus is a cause of infection of the CNS in patients from Cordoba. This study contributes to the epidemiology of encephalitis, as well as to patient management.

  10. Eye and Periocular Skin Involvement in Herpes Zoster Infection.

    Science.gov (United States)

    Kalogeropoulos, Chris D; Bassukas, Ioannis D; Moschos, Marilita M; Tabbara, Khalid F

    2015-01-01

    Herpes zoster ophthalmicus (HZO) is a clinical manifestation of the reactivation of latent varicella zoster virus (VZV) infection and is more common in people with diminished cell-mediated immunity. Lesions and pain correspond to the affected dermatomes, mostly in first or second trigeminal branch and progress from maculae, papules to vesicles and form pustules, and crusts. Complications are cutaneous, visceral, neurological, ocular, but the most debilitating is post-herpetic neuralgia. Herpes zoster ophthalmicus may affect all the ophthalmic structures, but most severe eye-threatening complications are panuveitis, acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN) as well. Antiviral medications remain the primary therapy, mainly useful in preventing ocular involvement when begun within 72 hours after the onset of the rash. Timely diagnosis and management of HZO are critical in limiting visual morbidity. Vaccine in adults over 60 was found to be highly effective to boost waning immunity what reduces both the burden of herpes zoster (HZ) disease and the incidence of post-herpetic neuralgia (PHN).

  11. Prophylactic Antiviral Treatment in Recurrent Herpes Zoster: A Case Report

    Directory of Open Access Journals (Sweden)

    Hatice Gamze Bayram

    2011-06-01

    Full Text Available Herpes zoster (HZ occurs in older ages with activation of varicella-zoster virus (VZV which persists in a dormant phase within the dorsal root ganglia. The incidence of HZ in immunosuppressed patients is 20-100 times higher and the clinical progress is more severe than in immunocompetent individuals. A 48-year-old man who had been diagnosed with acute myelocytic leukemia type M3 and had been treated with immunosuppressive agents was admitted to our clinic. The patient was clinically diagnosed as having HZ. He was treated with acyclovir 800 mg five times daily for 7 days. In the consecutive three months, he attended our clinic again with similar complaints. The left cervical (C5, C6 dermatomes were involved at the fourth attack of HZ. Multinucleated giant cells were determined on the Tzanck smear. VZV DNA was detected by polymerase chain reaction (PCR. Treatment with valacyclovir 1 g three times daily for 14 days was prescribed and then, prophylactic treatment with valacyclovir 500 mg two times a day was administered. Although immunosuppressive treatment was continued, no new attacks of herpes zoster occurred. We think that prophylactic antiviral therapy should be initiated in immunosuppressive individuals who have recurrent herpes zoster attacks.

  12. Seronegative Herpes simplex Associated Esophagogastric Ulcer after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Edouard Matevossian

    2008-03-01

    Full Text Available Herpes simplex infection is characterized by acute or subacute infection, often followed by a chronic carrier state. Consecutive recurrences may flare up if immunocompromise occurs. Herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm, HIV/AIDS or therapeutically induced immune deficiency. Here we report the case of an HSV-DNA seronegative patient who developed grade III dysphagia 13 days after allogeneic liver transplantation. Endoscopy revealed an esophageal-gastric ulcer, and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection. Immunohistochemistry staining revealed a distinct nuclear positive anti-HSV reaction. Antiviral therapy with acyclovir and high-dose PPI led to a complete revision of clinical symptoms within 48 h. Repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction. Although the incidence of post-transplantation Herpes simplex induced gastroesophageal disease is low, the viral HSV ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if HSV-DNA PCR is negative.

  13. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    Directory of Open Access Journals (Sweden)

    Paula A. Suazo

    2015-01-01

    Full Text Available Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1 and herpes simplex virus-2 (HSV-2 infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency.

  14. Evasion of early antiviral responses by herpes simplex viruses.

    Science.gov (United States)

    Suazo, Paula A; Ibañez, Francisco J; Retamal-Díaz, Angello R; Paz-Fiblas, Marysol V; Bueno, Susan M; Kalergis, Alexis M; González, Pablo A

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency.

  15. Shared ancestry of herpes simplex virus 1 strain Patton with recent clinical isolates from Asia and with strain KOS63.

    Science.gov (United States)

    Pourchet, Aldo; Copin, Richard; Mulvey, Matthew C; Shopsin, Bo; Mohr, Ian; Wilson, Angus C

    2017-12-01

    Herpes simplex virus 1 (HSV-1) is a widespread pathogen that persists for life, replicating in surface tissues and establishing latency in peripheral ganglia. Increasingly, molecular studies of latency use cultured neuron models developed using recombinant viruses such as HSV-1 GFP-US11, a derivative of strain Patton expressing green fluorescent protein (GFP) fused to the viral US11 protein. Visible fluorescence follows viral DNA replication, providing a real time indicator of productive infection and reactivation. Patton was isolated in Houston, Texas, prior to 1973, and distributed to many laboratories. Although used extensively, the genomic structure and phylogenetic relationship to other strains is poorly known. We report that wild type Patton and the GFP-US11 recombinant contain the full complement of HSV-1 genes and differ within the unique regions at only eight nucleotides, changing only two amino acids. Although isolated in North America, Patton is most closely related to Asian viruses, including KOS63. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Recombinant Collagenlike Proteins

    Science.gov (United States)

    Fertala, Andzej

    2007-01-01

    A group of collagenlike recombinant proteins containing high densities of biologically active sites has been invented. The method used to express these proteins is similar to a method of expressing recombinant procollagens and collagens described in U. S. Patent 5,593,859, "Synthesis of human procollagens and collagens in recombinant DNA systems." Customized collagenous proteins are needed for biomedical applications. In particular, fibrillar collagens are attractive for production of matrices needed for tissue engineering and drug delivery. Prior to this invention, there was no way of producing customized collagenous proteins for these and other applications. Heretofore, collagenous proteins have been produced by use of such biological systems as yeasts, bacteria, and transgenic animals and plants. These products are normal collagens that can also be extracted from such sources as tendons, bones, and hides. These products cannot be made to consist only of biologically active, specific amino acid sequences that may be needed for specific applications. Prior to this invention, it had been established that fibrillar collagens consist of domains that are responsible for such processes as interaction with cells, binding of growth factors, and interaction with a number of structural proteins present in the extracellular matrix. A normal collagen consists of a sequence of domains that can be represented by a corresponding sequence of labels, e.g., D1D2D3D4. A collagenlike protein of the present invention contains regions of collagen II that contain multiples of a single domain (e.g., D1D1D1D1 or D4D4D4D4) chosen for its specific biological activity. By virtue of the multiplicity of the chosen domain, the density of sites having that specific biological activity is greater than it is in a normal collagen. A collagenlike protein according to this invention can thus be made to have properties that are necessary for tissue engineering.

  17. Chloroquine diphosphate: a risk factor for herpes zoster in patients with dermatomyositis/polymyositis

    Directory of Open Access Journals (Sweden)

    Gilmara Franco da Cunha

    2013-05-01

    Full Text Available OBJECTIVES: Herpes zoster has been widely described in the context of different systemic autoimmune diseases but not dermatomyositis/polymyositis. Therefore, we analyzed the prevalence, risk factors and herpes zoster outcomes in this population. METHOD: A retrospective cohort study of herpes zoster infections in dermatomyositis/polymyositis patients was performed. The patients were followed at a tertiary center from 1991 to 2012. For the control group, each patient with herpes zoster was paired with two patients without herpes zoster. Patients were matched by gender and the type of myositis, age at myositis onset and disease duration. RESULTS: Of 230 patients, 24 (10.4% had a histories of herpes zoster (19 with dermatomyositis and five with polymyositis, two-thirds female. The mean age of the patients with herpes zoster was 44.6±16.8 years. No difference between the groups was found regarding cumulative clinical manifestations. Disease activity, autoantibody, muscle and leukogram parameters were also comparable between the groups. No differences in immunosuppressive (alone or in association with other immunosuppressive therapies or glucocorticoid (current use, medium dose and cumulative dose in the last two months therapies were found between patients with and without herpes zoster. However, a higher proportion of patients in the herpes zoster group received chloroquine diphosphate compared to the control group. All of the patients received acyclovir; 58.3% of patients had postherpetic neuralgia and no cases of recurrence were reported. Furthermore, individuals who were taking high prednisone doses at the time of the herpes zoster diagnosis had reduced levels of postherpetic neuralgia. CONCLUSIONS: These data suggest that chloroquine diphosphate could predispose patients with dermatomyositis/polymyositis to developing herpes zoster, particularly women and dermatomyositis patients.

  18. Distrofia simpática reflexa pós herpes zoster Reflex sympathetic dystrophy following herpes zoster

    Directory of Open Access Journals (Sweden)

    Catia Susana Harumi Minami

    2004-08-01

    Full Text Available A distrofia simpática reflexa (DSR é uma síndrome dolorosa pouco entendida que consiste na presença de múltiplos sinais e sintomas incluindo dor, edema, alterações cutâneas distróficas e disfunção autonômica envolvendo uma ou mais extremidades. Nem sempre a DSR pós-herpes zóster é facilmente reconhecida. Poucos relatos dessa complicação foram publicados, o que torna interessante esta descrição. Apresentamos o caso de uma mulher branca, de 65 anos de idade cujos sinais e sintomas característicos de DSR no membro superior direito surgiram após 4 semanas do aparecimento das lesões de herpes zóster envolvendo trajeto dermatomérico. Com o diagnóstico precoce e abordagem terapêutica com calcitonina nasal e fisioterapia houve melhoras funcional e álgica satisfatórias em um mês de tratamento.The reflex sympathetic dystrophy (RSD is a poorly understood, painful syndrome that consists of multiple clinical manifestations, including pain, swelling, dystrophic cutaneous changes and autonomic dysfunction involving one or more extremities. The RSD following herpes zoster is not always easily recognized, and only a few documented cases of this complication have been reported, what makes this report even more interesting. We present the case of a 65 years old white woman, with characteristic signs and symptoms of RSD in the right upper limb observed four weeks after she had had a typical herpes zoster involving the dermatomes. Early diagnosis and treatment with intranasal calcitonin and physiotherapy lead to progressive functional and pain improvements after one month.

  19. The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.

    Science.gov (United States)

    Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang

    2014-01-01

    The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.

  20. Cell biology of mitotic recombination

    DEFF Research Database (Denmark)

    Lisby, Michael; Rothstein, Rodney

    2015-01-01

    Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules...... as well as the cellular organization of the process of homologous recombination. Herein we review the cell biological aspects of mitotic homologous recombination with a focus on Saccharomyces cerevisiae and mammalian cells, but will also draw on findings from other experimental systems. Key topics...

  1. Laboratory diagnosis and epidemiology of herpes simplex 1 and 2 genital infections.

    Science.gov (United States)

    Glinšek Biškup, Urška; Uršič, Tina; Petrovec, Miroslav

    2015-01-01

    Herpes simplex virus types 1 and 2 are the main cause of genital ulcers worldwide. Although herpes simplex virus type 2 is the major cause of genital lesions, herpes simplex virus type 1 accounts for half of new cases in developed countries. Herpes simplex virus type 2 seroprevalence rises with sexual activity from adolescence through adulthood. Slovenian data in a high-risk population shows 16% seroprevalence of HSV-2. HSV-1 and HSV-2 DNA in genital swabs was detected in 19% and 20.7%, respectively. In most cases, genital herpes is asymptomatic. Primary genital infection with herpes simplex virus types 1 and 2 can be manifested by a severe clinical picture, involving the vesicular skin and mucosal changes and ulcerative lesions of the vulva, vagina, and cervix in women and in the genital region in men. Direct methods of viral genome detection are recommended in the acute stage of primary and recurrent infections when manifest ulcers or lesions are evident. Serological testing is recommended as an aid in diagnosing genital herpes in patients with reinfection in atypical or already healed lesions. When herpes lesions are present, all sexual activities should be avoided to prevent transmission of infection. Antiviral drugs can reduce viral shedding and thus reduce the risk of sexual transmission of the virus.

  2. Cesarean Delivery in Women With Genital Herpes in Washington State, 1989–1991

    Directory of Open Access Journals (Sweden)

    Jeanne M. Marrazzo

    1997-01-01

    Full Text Available Objective: The purpose of this study was to determine whether the proportion of cesarean deliveries in pregnant women with a history of genital herpes and no active lesions at birth is higher than that in women with no history of genital herpes, and to determine whether this risk was modified by birth facilities' underlying prevalence of cesarean delivery.

  3. Seroprevalences of herpes simplex virus type 1 and type 2 among pregnant women in the Netherlands.

    NARCIS (Netherlands)

    Gaytant, M.A.; Steegers, E.A.P.; Laere, M. van; Semmekrot, B.A.; Groen, J.; Weel, J.F.; Meijden, W.I. van der; Boer, K.; Galama, J.M.D.

    2002-01-01

    BACKGROUND: In the Netherlands 73% of cases of neonatal herpes are caused by herpes simplex virus type 1 (HSV-1), whereas in the United States a majority are caused by HSV type 2 (HSV-2).GOAL To understand this difference we undertook a seroepidemiological study on the prevalence of HSV-1 and HSV-2

  4. Seroprevalences of herpes simplex virus type 1 and type 2 among pregnant women in the Netherlands

    NARCIS (Netherlands)

    Gaytant, Michael A.; Steegers, Eric A. P.; van Laere, Marloes; Semmekrot, Ben A.; Groen, Jan; Weel, Jan F.; van der Meijden, Willem I.; Boer, Kees; Galama, Jochem M. D.

    2002-01-01

    BACKGROUND: In the Netherlands 73% of cases of neonatal herpes are caused by herpes simplex virus type 1 (HSV-1), whereas in the United States a majority are caused by HSV type 2 (HSV-2). GOAL To understand this difference we undertook a seroepidemiological study on the prevalence of HSV-1 and HSV-2

  5. On the Issue of Herpes Infection as an Actual Problem Nowadays

    Directory of Open Access Journals (Sweden)

    V.P. Borak

    2016-04-01

    Full Text Available Among persistent intracellular agents, a group of herpesviruses occupies the leading place after the prevalence. The World Health Organization (WHO warns the international community of the danger of latent herpes infection pandemic. According to the WHO, 70 to 90 % of the world population is infected with one or more types of herpes virus, and in 50 % of them, due to the absence of stable immunity, disease relapses occur annually. The family of herpes viruses found in humans includes herpes simplex virus type 1 and 2, Zoster virus, cytomegalovirus, Epstein-Barr virus, human herpes type 6, 7, 8. Thus, in the pathogenesis of herpes infection type 1 and 2, there are four main phases: the penetration of the epithelial cells → penetration into the nerve endings and paravertebral ganglia → elimination of the virus from tissues and organs → reactivation of herpes simplex virus and moving it to the port of infection. Herpetic and cytomegalovirus infection that belongs to the group of TORCH infections is the most common cause fetal infection, which can lead to the birth of a child with disabilities. Herpesvirus infections are considered as a group of infections associated with human immunodeficiency syndrome, and is a common cause of damage to the central nervous system and internal organs in patients with secondary immunodeficiency. Almost all known now human herpesviruses can cause damage to the nervous system. In this regard, herpes infections have become one of the leading medical and social problems and acquire national importance.

  6. Prevalence of intrathecal acyclovir resistant virus in herpes simplex encephalitis patients

    NARCIS (Netherlands)

    J.G. Mitterreiter (Johanna G.); M.J. Titulaer (Maarten); G.P. van Nierop (Gijs); J.J.A. van Kampen (Jeroen); G.I. Aron (Georgina); A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George); W.J.D. Ouwendijk (Werner )

    2016-01-01

    textabstractHerpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted

  7. Detection of Human Herpes Virus 8 in Kaposi's sarcoma tissues at ...

    African Journals Online (AJOL)

    Introduction: Human herpes virus-8, a γ2-herpes virus, is the aetiological agent of Kaposi sarcoma. Recently, Kaposi's sarcoma cases have increased in Zambia. However, the diagnosis of this disease is based on morphological appearance of affected tissues using histological techniques, and the association with its ...

  8. Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster.

    Science.gov (United States)

    Kim, Choon Kwan; Choi, Youn Mi; Bae, Eunsin; Jue, Mihn Sook; So, Hyung Seok; Hwang, Eung-Soo

    2018-01-01

    The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (Pherpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster.

  9. Herpes zoster-associeret morbiditet hos børn i kemoterapi for akut lymfoblastaer leukaemi

    DEFF Research Database (Denmark)

    Sørensen, Gitte Vrelits; Helgestad, Jon; Rosthøj, Steen

    2009-01-01

    INTRODUCTION: Herpes zoster rarely occurs in healthy children, but may occur frequently and may take a complicated course in children receiving chemotherapy. We aimed to assess morbidity from herpes zoster in children with acute lymphoblastic leukemia (ALL). MATERIAL AND METHODS: Reviewing records...

  10. Study of Herpes Zoster in a Self-Referral Out-Patient Clinic ...

    African Journals Online (AJOL)

    Aim: To study the presentation of herpes zoster (shingles) in self-referral urban primary care setting. Patients and method: During nearly 20 years, patients of Igbo ethnic group presented with herpes zoster, on a self-referral basis, to my urban, week day evening, out patient clinic. The recorded epidemiological parameters ...

  11. Herpes simplex virus internalization into epithelial cells requires Na+/H+ exchangers and p21-activated kinases but neither clathrin- nor caveolin-mediated endocytosis.

    Science.gov (United States)

    Devadas, Deepika; Koithan, Thalea; Diestel, Randi; Prank, Ute; Sodeik, Beate; Döhner, Katinka

    2014-11-01

    Herpes simplex virus 1 (HSV-1) is an alphaherpesvirus that has been reported to infect some epithelial cell types by fusion at the plasma membrane but others by endocytosis. To determine the molecular mechanisms of productive HSV-1 cell entry, we perturbed key endocytosis host factors using specific inhibitors, RNA interference (RNAi), or overexpression of dominant negative proteins and investigated their effects on HSV-1 infection in the permissive epithelial cell lines Vero, HeLa, HEp-2, and PtK2. HSV-1 internalization required neither endosomal acidification nor clathrin- or caveolin-mediated endocytosis. In contrast, HSV-1 gene expression and internalization were significantly reduced after treatment with 5-(N-ethyl-N-isopropyl)amiloride (EIPA). EIPA blocks the activity of Na(+)/H(+) exchangers, which are plasma membrane proteins implicated in all forms of macropinocytosis. HSV-1 internalization furthermore required the function of p21-activated kinases that contribute to macropinosome formation. However, in contrast to some forms of macropinocytosis, HSV-1 did not enlist the activities of protein kinase C (PKC), tyrosine kinases, C-terminal binding protein 1, or dynamin to activate its internalization. These data suggest that HSV-1 depends on Na(+)/H(+) exchangers and p21-activated kinases either for macropinocytosis or for local actin rearrangements required for fusion at the plasma membrane or subsequent passage through the actin cortex underneath the plasma membrane. After initial replication in epithelial cells, herpes simplex viruses (HSVs) establish latent infections in neurons innervating these regions. Upon primary infection and reactivation from latency, HSVs cause many human skin and neurological diseases, particularly in immunocompromised hosts, despite the availability of effective antiviral drugs. Many viruses use macropinocytosis for virus internalization, and many host factors mediating this entry route have been identified, although the

  12. Significance of tear β2-MG radioimmunoassay in herpes simplex keratitis

    International Nuclear Information System (INIS)

    Feng Zhuxu; Zhao Suzhen; Zhang Qiliang; Chen Fengfen; Tang Baoyi

    1994-01-01

    Levels of tear and serum β 2 -MG are determined with radioimmunoassay in 35 patients with herpes simplex keratitis and 40 normal subjects. The results show that tear β 2 -MG levels of patients with herpes simplex keratitis (13.21 +- 6.15 mg/l) and normal subjects (8.43 +- 1.52 mg/l) are significantly different (P 2 -MG levels of tear and that of serum in normal subjects (P 2 -MG levels of tear and that of serum in patients with herpes simplex keratitis (P 2 -MG levels of patients with herpes simplex keratitis and that of normal subjects (P>0.05). The β 2 -MG levels of tear is higher than that of serum in normal subjects which reflects more correctly immune condition of patients with herpes simplex keratitis than that of serum

  13. Hadron Correlations and Parton Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Fries, R.J. [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)]. E-mail: rjfries@comp.tamu.edu

    2007-02-15

    Parton recombination has been found to be an extremely useful model to understand hadron production at the Relativistic Heavy Ion Collider. It is particularly important to explore its connections with hard processes. This article reviews some of the aspects of the quark recombination model and places particular emphasis on hadron correlations.

  14. Update on Neonatal Herpes Simplex Epidemiology in the Netherlands: A Health Problem of Increasing Concern?

    Science.gov (United States)

    van Oeffelen, Louise; Biekram, Manisha; Poeran, Jashvant; Hukkelhoven, Chantal; Galjaard, Sander; van der Meijden, Wim; Op de Coul, Eline

    2018-01-18

    This paper provides an update on the incidence of neonatal herpes, guideline adherence by health care professionals (HCP), and trends in genital herpes simplex virus (HSV) infection during pregnancy in the Netherlands. Questionnaires were sent to all hospitals inquiring about numbers and characteristics of neonatal and maternal HSV infections, and guideline adherence between 2012 and 2015. Longitudinal trends were investigated from 1999 onwards using survey data and Perinatal Registry of the Netherlands data (Perined). Trends were smoothed with Poisson regression splines. Risk indicators for neonatal and maternal HSV infections were examined with Poisson regression analyses. Neonatal herpes incidence was 4.8/100,000 live births based on survey data (2012-2015) and 3.4/100,000 based on Perined (2012-2014). Mortality rate was 23% (7/30). Neonatal herpes incidence increased slightly over time as did the prevalence of genital HSV infection among pregnant women. Non-Western ethnicity (RR 1.9, 95%CI 1.5-2.5) and age herpes during pregnancy. In Perined, none of the neonatal herpes cases had a mother diagnosed with an active genital herpes infection during pregnancy. Preventive measures to reduce vertical herpes transmission (such as caesarean section) were less commonly reported by HCP in 2012-2015 compared to 2006-2011. Neonatal herpes incidence in the Netherlands slowly increased over the last 15 years. An increased genital HSV prevalence during pregnancy or, to lower extent, the decreased guideline adherence by HCP may be responsible. A rise in asymptomatic maternal HSV shedding is also plausible, emphasizing the challenges in preventing neonatal herpes.

  15. Herpes Zoster and Dementia: A Nationwide Population-Based Cohort Study.

    Science.gov (United States)

    Chen, Vincent Chin-Hung; Wu, Shu-I; Huang, Kuo-You; Yang, Yao-Hsu; Kuo, Ting-Yu; Liang, Hsin-Yi; Huang, Kuan-Lun; Gossop, Michael

    Some infectious diseases have been found to be associated with cognitive impairment and dementia. However, the relationship between herpes zoster and dementia has received little attention. This study aimed to investigate this association as well as associations of antiviral treatments for herpes zoster and incident dementia using a large national sample. Cases were identified from the Taiwan National Health Insurance Research Database with a new diagnosis of herpes zoster (ICD-9-CM code: 053) between 1997 and 2013. Each identified individual with a case of herpes zoster was compared with 1 sex-, age-, and residence-matched control subject. Both groups were followed until the first diagnosis of dementia (ICD-9-CM codes: 290.0 to 290.4, 294.1, 331.0 to 331.2, and 331.82), withdrawal from the registry, or the end of 2013. Cox regression analyses and competing risk model were applied, adjusting for sex, age, residence, depression, autoimmune disease, ischemic stroke, traumatic brain injury, alcohol use disorder, and antiviral treatments for herpes zoster to evaluate the risk of interest. A total of 39,205 cases with herpes zoster were identified. Of the 78,410 study and comparison subjects, 4,204 were diagnosed as having dementia during a mean (SD) follow-up period of 6.22 (4.05) years. Herpes zoster was associated with a slightly increased risk of dementia in the fully adjusted model (hazard ratio [HR] = 1.11; 95% CI, 1.04-1.17). Prescriptions of antiviral therapy were associated with a reduced risk of developing dementia following the diagnosis of herpes zoster (HR = 0.55; 95% CI, 0.40-0.77). Herpes zoster was associated with an increased risk of dementia, independent of potential confounding factors. Antiviral treatment might be protective in preventing dementia in patients with herpes zoster. © Copyright 2017 Physicians Postgraduate Press, Inc.

  16. RNA interference inhibits herpes simplex virus type 1 isolated from saliva samples and mucocutaneous lesions.

    Science.gov (United States)

    Silva, Amanda Perse da; Lopes, Juliana Freitas; Paula, Vanessa Salete de

    2014-01-01

    The aim of this study was to evaluate the use of RNA interference to inhibit herpes simplex virus type-1 replication in vitro. For herpes simplex virus type-1 gene silencing, three different small interfering RNAs (siRNAs) targeting the herpes simplex virus type-1 UL39 gene (sequence si-UL 39-1, si-UL 39-2, and si-UL 39-3) were used, which encode the large subunit of ribonucleotide reductase, an essential enzyme for DNA synthesis. Herpes simplex virus type-1 was isolated from saliva samples and mucocutaneous lesions from infected patients. All mucocutaneous lesions' samples were positive for herpes simplex virus type-1 by real-time PCR and by virus isolation; all herpes simplex virus type-1 from saliva samples were positive by real-time PCR and 50% were positive by virus isolation. The levels of herpes simplex virus type-1 DNA remaining after siRNA treatment were assessed by real-time PCR, whose results demonstrated that the effect of siRNAs on gene expression depends on siRNA concentration. The three siRNA sequences used were able to inhibit viral replication, assessed by real-time PCR and plaque assays and among them, the sequence si-UL 39-1 was the most effective. This sequence inhibited 99% of herpes simplex virus type-1 replication. The results demonstrate that silencing herpes simplex virus type-1 UL39 expression by siRNAs effectively inhibits herpes simplex virus type-1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative. Copyright © 2014. Published by Elsevier Editora Ltda.

  17. Concurrent reactivation of herpes simplex and varicella zoster viruses confirmed by the loop-mediated isothermal amplification assay.

    Science.gov (United States)

    Kobayashi, Tsukane; Yagami, Akiko; Suzuki, Kayoko; Yoshikawa, Tetsushi; Matsunaga, Kayoko

    2014-01-01

    Concurrent reactivation of herpes simplex and varicella zoster viruses is rare. Here, we describe the case of an elderly patient with herpes labialis and herpes zoster manifesting as a right-side facial eruption with vesicles and crusting. The loop-mediated isothermal amplification (LAMP) assay demonstrated the presence of both herpes simplex virus type 1 and varicella zoster virus in swab samples taken from the face, which was confirmed by real-time PCR, suggesting concurrent reactivation of both viruses. The use of the LAMP assay in the present case indicates its usefulness in the diagnosis of atypical herpes infections.

  18. Evaluation of the HerpeSelect Express rapid test in the detection of herpes simplex virus type 2 antibodies in patients with genital ulcer disease.

    Science.gov (United States)

    Al-Shobaili, Hani; Hassanein, Khaled M; Mostafa, Marwa Salah; Al Duways, Ali Saleh

    2015-01-01

    A rapid point-of-care test with high sensitivity and specificity is required in order to fulfill the need for early detection and screening of Herpes simplex virus type 2 (HSV-2) infection among patients with genital ulcer disease (GUD), for better management and control of virus transmission. The goal of this study is to evaluate the performance of the commercially available HerpeSelect Express rapid test in comparison with three ELISA assays: HerpeSelect ELISA, Kalon HSV-2 glycoprotein G2 assay, and monoclonal antibody blocking enzyme immunoassay, which was used as the gold standard for the detection of HSV-2 antibodies. This study showed high sensitivity (ranging from 82.6 to 100%) and specificity (100%) of the HerpeSelect Express rapid test when compared to the three ELISA assays. The agreement between the HerpeSelect Express rapid test with the three ELISAs ranged from 93.3 to 100%. The HerpeSelect Express rapid test has adequate sensitivity and specificity for confirming HSV-2 infection in patients with GUD, indicating its suitability for epidemiological studies. © 2014 Wiley Periodicals, Inc.

  19. Genital Herpes: Insights into Sexually Transmitted Infectious Disease.

    Science.gov (United States)

    Jaishankar, Dinesh; Shukla, Deepak

    2016-06-27

    Etiology, transmission and protection: Herpes simplex virus-2 (HSV-2) is a leading cause of sexually transmitted infections with recurring manifestations throughout the lifetime of infected hosts. Currently no effective vaccines or prophylactics exist that provide complete protection or immunity from the virus, which is endemic throughout the world. Pathology/Symptomatology: Primary and recurrent infections result in lesions and inflammation around the genital area and the latter accounts for majority of genital herpes instances. Immunocompromised patients including neonates are susceptible to additional systemic infections including debilitating consequences of nervous system inflammation. Epidemiology, incidence and prevalence: More than 500 million people are infected worldwide and most reported cases involve the age groups between 16-40 years, which coincides with an increase in sexual activity among this age group. While these numbers are an estimate, the actual numbers may be underestimated as many people are asymptomatic or do not report the symptoms. Treatment and curability: Currently prescribed medications, mostly nucleoside analogs, only reduce the symptoms caused by an active infection, but do not eliminate the virus or reduce latency. Therefore, no cure exists against genital herpes and infected patients suffer from periodic recurrences of disease symptoms for their entire lives. Molecular mechanisms of infection: The last few decades have generated many new advances in our understanding of the mechanisms that drive HSV infection. The viral entry receptors such as nectin-1 and HVEM have been identified, cytoskeletal signaling and membrane structures such as filopodia have been directly implicated in viral entry, host motor proteins and their viral ligands have been shown to facilitate capsid transport and many host and HSV proteins have been identified that help with viral replication and pathogenesis. New understanding has emerged on the role of

  20. Sequential analysis of CT findings in herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Kawamura, Mitsuru; Tokumaru, Yukio; Ito, Naoki; Yamada, Tatsuo; Hirayama, Keizo

    1982-01-01

    CT findings of six patients with serologically confirmed herpes simplex encephalitis were analyzed sequentially. The initial change in CT scan in 3 cases was generalized cerebral edema instead of low density areas in the anterior temporal lobes, which have generally been known as the initial findings. Then, bilateral (5 cases) or unilateral (1 case) island-shaped low absorption areas in the insular cortex and the claustrum appeared within 10 days of onset in all 6 cases. These findings, especially the latter, seem to be characteristic of the acute stage and useful in the early diagnosis of herpes simplex encephalitis. The low density areas, then, spread to the temporal lobes, rectal and cingulate gyri in the subacute stage (3 cases) and finally to the frontal and occipital lobes in the chronic stage (2 cases). In the basal ganglia, thalamus, brain stem and cerebellum, however, there were no low density areas. In 2 cases there was no progression of low density areas beyond those of the acute stage. In one case there were high density areas in the temporal lobes and parapontine cisterns bilaterally. This could correspond to the pathological findings in herpes simplex encephalitis. The improvement of CT findings (or arrest at the early stage) was noted in 2 cases in which the clinical state also improved. This might well be the effect of adenine arabinoside. The one case treated with cytosine arabinoside had extensive low density areas in CT and finally died. The importance of CT in the evaluation of adenine arabinoside therapy was stressed. (author)

  1. Genital Herpes: Insights into Sexually Transmitted Infectious Disease

    Science.gov (United States)

    Jaishankar, Dinesh; Shukla, Deepak

    2016-01-01

    Etiology, transmission and protection: Herpes simplex virus-2 (HSV-2) is a leading cause of sexually transmitted infections with recurring manifestations throughout the lifetime of infected hosts. Currently no effective vaccines or prophylactics exist that provide complete protection or immunity from the virus, which is endemic throughout the world. Pathology/Symptomatology: Primary and recurrent infections result in lesions and inflammation around the genital area and the latter accounts for majority of genital herpes instances. Immunocompromised patients including neonates are susceptible to additional systemic infections including debilitating consequences of nervous system inflammation. Epidemiology, incidence and prevalence: More than 500 million people are infected worldwide and most reported cases involve the age groups between 16-40 years, which coincides with an increase in sexual activity among this age group. While these numbers are an estimate, the actual numbers may be underestimated as many people are asymptomatic or do not report the symptoms. Treatment and curability: Currently prescribed medications, mostly nucleoside analogs, only reduce the symptoms caused by an active infection, but do not eliminate the virus or reduce latency. Therefore, no cure exists against genital herpes and infected patients suffer from periodic recurrences of disease symptoms for their entire lives. Molecular mechanisms of infection: The last few decades have generated many new advances in our understanding of the mechanisms that drive HSV infection. The viral entry receptors such as nectin-1 and HVEM have been identified, cytoskeletal signaling and membrane structures such as filopodia have been directly implicated in viral entry, host motor proteins and their viral ligands have been shown to facilitate capsid transport and many host and HSV proteins have been identified that help with viral replication and pathogenesis. New understanding has emerged on the role of

  2. Evolutionary origins of human herpes simplex viruses 1 and 2.

    Science.gov (United States)

    Wertheim, Joel O; Smith, Martin D; Smith, Davey M; Scheffler, Konrad; Kosakovsky Pond, Sergei L

    2014-09-01

    Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus-host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two-thirds of the human population infected by at least one virus. Here, we investigated whether the additional human simplex virus is the result of ancient viral lineage duplication or cross-species transmission. We found that standard phylogenetic models of nucleotide substitution are inadequate for distinguishing among these competing hypotheses; the extent of synonymous substitutions causes a substantial underestimation of the lengths of some of the branches in the phylogeny, consistent with observations in other viruses (e.g., avian influenza, Ebola, and coronaviruses). To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment. This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct Homo precursor of modern humans, around 1.6 Ma. These results provide a new framework for understanding human herpes simplex virus evolution and demonstrate the importance of using selection-informed models of sequence evolution when investigating viral origin hypotheses. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Herpes zoster sciatica mimicking lumbar canal stenosis: a case report.

    Science.gov (United States)

    Koda, Masao; Mannoji, Chikato; Oikawa, Makiko; Murakami, Masazumi; Okamoto, Yuzuru; Kon, Tamiyo; Okawa, Akihiko; Ikeda, Osamu; Yamazaki, Masashi; Furuya, Takeo

    2015-07-29

    Symptom of herpes zoster is sometimes difficult to distinguish from sciatica induced by spinal diseases, including lumbar disc herniation and spinal canal stenosis. Here we report a case of sciatica mimicking lumbar canal stenosis. A 74-year-old Chinese male patient visited our hospital for left-sided sciatic pain upon standing or walking for 5 min of approximately 1 month's duration. At the first visit to our hospital, there were no skin lesions. A magnetic resonance imaging showed spinal canal stenosis between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with sciatica induced by spinal canal stenosis. We considered decompression surgery for the stenosis of 4th and 5th lumbar spine because conservative therapy failed to relieve the patient's symptom. At that time, the patient complained of a skin rash involving his left foot for several days. A vesicular rash and erythema were observed on the dorsal and plantar surfaces of the great toe and lateral malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar spinal nerve area based on clinical findings, including the characteristics of the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti-inflammatory drugs. After 1 week of medication, the skin rash resolved and pain relief was obtained. In conclusion, spinal surgeons should keep in mind herpes zoster infection as one of the possible differential diagnoses of sciatica, even if there is no typical skin rash.

  4. Topical therapy of recurrent herpes - acyclovir versus tromantidine

    Directory of Open Access Journals (Sweden)

    Kumar Bhushan

    1991-01-01

    Full Text Available Fifty men with recurrent genital herpes were treated with either acyclovir 5% cream or tromantidine 1 % ointment applied topically. Acyclovir cream was applied 5 times and tromantidine cream 4 times daily for 5 days. At least one pre-treatment episode was observed by one of the authors. Self assessment charts were provided to the patients to record prodromal symptoms and healing time. For comparison at least 3 post treatment episodes were observed and com-pared with mean healing time of 3 pre-treatment episodes. Both acyclovir cream and tromantidine ointment significantly reduced the duration of prodrome, hastened healing and so reduced mean healing time.

  5. An Unusual Presentation of Herpes Simplex Virus Encephalitis

    Directory of Open Access Journals (Sweden)

    Ray Boyapati

    2012-01-01

    Full Text Available We present a case of a 65-year-old man with an acute alteration in mental state that was initially diagnosed as a functional psychiatric condition. After extensive workup, herpes simplex virus type 1 (HSV-1 was detected in the patient’s cerebrospinal fluid (CSF by polymerase chain reaction (PCR, and he responded rapidly to treatment with acyclovir. The case illustrates the importance of actively excluding organic causes in such patients, the need to have a low threshold of suspicion for HSV encephalitis, and the central role of CSF PCR testing for the diagnosis of HSV encephalitis, even in the absence of CSF biochemical abnormalities.

  6. Herpes Zoster Involving Penis and Scrotum: An Unusual Occurrence

    International Nuclear Information System (INIS)

    Arshad, A. R.; Alvi, K. Y.; Chaudhary, A. A.

    2015-01-01

    Herpes zoster is an infectious vesicular skin rash in a dermatomal distribution caused by Varicella zoster virus. It occurs very uncommonly in sacral dermatomes. We describe a case with rash on penis and scrotum due to involvement of S2 dermatome in a young male. The disease followed an uneventful course and the patient recovered completely without any sequelae or complications. This case is being presented to highlight its unusual location and to discuss differentiation from another viral infection commonly seen at this site. (author)

  7. Heat shock and herpes virus: enhanced reactivation without untargeted mutagenesis

    International Nuclear Information System (INIS)

    Lytle, C.D.; Carney, P.G.

    1988-01-01

    Enhanced reactivation of Ultraviolet-irradiated virus has been reported to occur in heat-shocked host cells. Since enhanced virus reactivation is often accompanied by untargeted mutagenesis, we investigated whether such mutagenesis would occur for herpes simplex virus (HSV) in CV-1 monkey kidney cells subjected to heat shock. In addition to expressing enhanced reactivation, the treated cells were transiently more susceptible to infection by unirradiated HSV. No mutagenesis of unirradiated HSV was found whether infection occurred at the time of increased susceptibility to infection or during expression of enhanced viral reactivation

  8. Hemorrhagic herpes encephalitis: A difficult diagnosis in computed tomography

    International Nuclear Information System (INIS)

    Neumann, N.U.; Albert, H.H. von

    1982-01-01

    Herpes simplex encephalitis (HSE) is the most common sporadically appearing encephalitis in Central Europe. Differential diagnosis to brain tumors or spontaneous intercerebral hemorrhage is difficult. There are CT scan findings which are characteristic of HSE but there are no pathognomonic patterns. These characteristic findings are helpful in differential diagnosis to neoplastic or vascular processes. Thus, other diagnostic procedures (i.e. brain biopsy) to confirm diagnosis of HSE and effective therapy may be carried out in time. The difficulties in differential diagnosis are shown by the presented case. (orig.) [de

  9. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

    International Nuclear Information System (INIS)

    Kaur, Amitinder; Sanford, Hannah B.; Garry, Deirdre; Lang, Sabine; Klumpp, Sherry A.; Watanabe, Daisuke; Bronson, Roderick T.; Lifson, Jeffrey D.; Rosati, Margherita; Pavlakis, George N.; Felber, Barbara K.; Knipe, David M.; Desrosiers, Ronald C.

    2007-01-01

    The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS

  10. Do herpes e suas implicações audiológicas: uma revisao de literatura Herpes and its hearing implications: a literature review

    Directory of Open Access Journals (Sweden)

    Larissa Cristina Schuster

    2009-12-01

    Full Text Available TEMA: herpes e audiologia. OBJETIVO: realizar revisão teórica principalmente sobre os vírus herpes simples tipo 1, herpes simples tipo 2 e varicela-zoster, bem como sobre seus efeitos na audição humana. Esses se constituem nos tipos de vírus herpéticos humanos de maior relevância para a área da Audiologia dentro da ciência da Fonoaudiologia e, no entanto, são pouco conhecidos e estudados, especialmente no Brasil. MÉTODOS: realizou-se pesquisa em bases de dados eletrônicas nacionais e internacionais, incluindo SciELO, MEDLINE e LILACS, a partir da seguinte combinação de descritores: herpes simplex/zoster X hearing loss ou deafness. Foram selecionados estudos publicados desde a década de 90 até os dias atuais, relevando-se aqueles que contivessem maior valor informativo, contribuindo para os objetivos do presente trabalho. CONCLUSÃO: os vírus herpéticos estudados apresentam estreita relação com distúrbios auditivos, independentemente da idade em que o sujeito é acometido.BACKGROUND: herpes and audiology. PURPOSE: to promote a theoretical approach mainly on herpes simplex virus type 1, herpes simplex virus type 2 and varicella zoster virus, and their effects on human hearing. Although representing the most relevant human herpetic viruses for the area of Audiology within the Speech and Language Pathology Science, these viruses are little studied and known, especially in Brazil. METHODS: a research was carried out in national and international electronic databases, including SciELO, MEDLINE and LILACS, and using the following keyword combinations: herpes simplex/zoster X hearing loss or deafness. Studies published from the 90's until today were selected, revealing those that would contain the highest informative value, which would thus contribute for the objectives of this work. CONCLUSION: the studied herpetic viruses show strict relation with hearing disorders, regardless of the age in which the patient is affected.

  11. Disruption of the p53-mediated G{sub 1}/S cell cycle checkpoint results in elevated rates of spontaneous genetic recombination in human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Strasfeld, L.; Brainerd, E.; Meyn, M.S. [Yale Univ. School of Medicine, New Haven, CT (United States)

    1994-09-01

    A key feature of the cancer-prone inherited disease ataxia-telangiectasia (A-T) is genetic instability. We recently demonstrated that one aspect of genetic instability in A-T is a marked elevation in the spontaneous rates of intrachromosomal mitotic recombination. We have proposed a model for A-T that attributes these high recombination rates to a lack of DNA damage-sensitive cell cycle checkpoints. One prediction of this model is that disrupting p53 function in normal cells should increase their spontaneous rates of recombination by interfering with their p53-dependent G{sub 1}/S cell cycle checkpoint. To test this prediction, we transfected control and A-T fibroblast lines that each harbor a single integrated copy of lacZ-based recombination vector (pLrec) with derivatives of a eukaryotic expression vector (pRep5) that contain either a dominant-negative p53 mutant (143{sup val{yields}ala}) or a human papilloma virus E6 gene (HPV18 E6). Expression of either of these genes results in loss of p53 function and abolition of the G{sub 1}/S cell cycle checkpoint. Four independent p53{sup 143ala} transformants of the control line showed 25-80 fold elevations in spontaneous recombination rates when compared to their parent cell line. Elevations in spontaneous recombination rates were also detected following transfection with the HPV18 E6 gene. In contrast, four independent p53{sup 143ala} transformants of the A-T cell line showed no significant changes in their already high spontaneous recombination rates. We are now extending these observations to additional normal human fibroblast lines and carrying out molecular analyses of the products of these recombinational events. Our results support our hypothesis that the lack of a p53-dependent G{sub 1}/S cell cycle checkpoint contributes to the hyperrecombination seen in A-T.

  12. Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

    Science.gov (United States)

    Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

    2007-07-01

    Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generated a strong p17-specific CD4+ T helper response preceding both p17-specific humoral and effector T cell responses. Moreover, we show that T0-p17 infection did not interfere with the endogenous processing of the transgene encoded antigen, since infected APCs were able to evoke a strong recall response in vitro. Our results demonstrate that replication-deficient HSV vectors can be appealing candidates for the development of vaccines able to trigger T helper responses.

  13. Genital herpes in children under 11 years and investigations for sexual abuse.

    Science.gov (United States)

    Reading, Richard; Hughes, Gwenda; Hill, Julia; Debelle, Geoff

    2011-08-01

    The implications for sexual abuse investigation of genital herpes in a child are uncertain because of a lack of good quality research evidence. The incidence, presenting features, history of exposure, indicators of child maltreatment and outcomes of child protection investigations in children with genital herpes are described. Ascertainment of all cases of genital herpes in children herpes simplex type 1, eight were tested for other sexually transmitted infections (STIs), and only one had a full STI screen. Three cases had other clinical features suggestive of sexual abuse. Six cases were referred for child protection investigation, but no sexual abuse was substantiated. Genital herpes in children under 11 years is rare. Almost a third of children diagnosed with genital herpes did not have appropriate virological investigation and few were screened for other STIs. Around a quarter of cases were referred to child protection agencies for further investigation, which limits any inferences in this study about mode of transmission in children. Sexual abuse guidance should emphasise the need for thorough assessment and investigation in cases of genital herpes in children.

  14. Isolation of herpes simplex virus from the genital tract during symptomatic recurrence on the buttocks.

    Science.gov (United States)

    Kerkering, Katrina; Gardella, Carolyn; Selke, Stacy; Krantz, Elizabeth; Corey, Lawrence; Wald, Anna

    2006-10-01

    To estimate the frequency of isolation of herpes simplex virus (HSV) from the genital tract when recurrent herpes lesions were present on the buttocks. Data were extracted from a prospectively observed cohort attending a research clinic for genital herpes infections between 1975 and 2001. All patients with a documented herpes lesion on the buttocks, upper thigh or gluteal cleft ("buttock recurrence") and concomitant viral cultures from genital sites including the perianal region were eligible. We reviewed records of 237 subjects, 151 women and 86 men, with a total of 572 buttock recurrences. Of the 1,592 days with genital culture information during a buttock recurrence, participants had concurrent genital lesions on 311 (20%, 95% confidence interval [CI] 14-27%) of these days. Overall, HSV was isolated from the genital region on 12% (95% CI 8-17%) of days during a buttock recurrence. In the absence of genital lesions, HSV was isolated from the genital area on 7% (95% CI 4%-11%) of days during a buttock recurrence and, among women, from the vulvar or cervical sites on 1% of days. Viral shedding of herpes simplex virus from the genital area is a relatively common occurrence during a buttock recurrence of genital herpes, even without concurrent genital lesions, reflecting perhaps reactivation from concomitant regions of the sacral neural ganglia. Patients with buttock herpes recurrences should be instructed about the risk of genital shedding during such recurrences. II-2.

  15. Hospitalizations realted to herpes zoster infection in the Canary Islands, Spain (2005-2014).

    Science.gov (United States)

    García-Rojas, Amós; Gil-Prieto, Ruth; Núñez-Gallo, Domingo Ángel; Matute-Cruz, Petra; Gil-de-Miguel, Angel

    2017-08-24

    Herpes zoster is an important problem of public health especially among the elderly in Spain. A population-based retrospective epidemiological study to estimate the burden of herpes zoster requiring hospitalization in the Canary Islands, Spain was conducted by using data from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos. Records of all patients admitted to hospital with a diagnosis of herpes zoster in any position and cases of primary diagnosis (ICD-9-MC codes 053.0-053.9) during a 10-year period (2005-2014), were selected. A total of 1088 hospitalizations with a primary or secondary diagnosis of herpes zoster were identified during the study period. Annually there were 6.99 hospitalizations by herpes zoster per 100,000 population. It increases with age reaching a maximum in persons ≥85 years of age (43.98 admissions per 100,000). Average length of hospitalization was 16 days and 73 patients died, with a case-fatality rate of 4.03%. In 22% of the cases hospitalized, herpes zoster was the primary diagnosis. The hospitalization burden of herpes zoster in adults in the Canary Islands was still important during the last decade and justify the implementation of preventive measures, like vaccination in the elderly or other high risk groups to reduce the most severe cases of the disease.

  16. Exploiting Herpes Simplex Virus Entry for Novel Therapeutics

    Directory of Open Access Journals (Sweden)

    Deepak Shukla

    2013-06-01

    Full Text Available Herpes Simplex virus (HSV is associated with a variety of diseases such as genital herpes and numerous ocular diseases. At the global level, high prevalence of individuals who are seropositive for HSV, combined with its inconspicuous infection, remains a cause for major concern. At the molecular level, HSV entry into a host cell involves multiple steps, primarily the interaction of viral glycoproteins with various cell surface receptors, many of which have alternate substitutes. The molecular complexity of the virus to enter a cell is also enhanced by the existence of different modes of viral entry. The availability of many entry receptors, along with a variety of entry mechanisms, has resulted in a virus that is capable of infecting virtually all cell types. While HSV uses a wide repertoire of viral and host factors in establishing infection, current therapeutics aimed against the virus are not as diversified. In this particular review, we will focus on the initial entry of the virus into the cell, while highlighting potential novel therapeutics that can control this process. Virus entry is a decisive step and effective therapeutics can translate to less virus replication, reduced cell death, and detrimental symptoms.

  17. Unusual Initial Presentation of Herpes Simplex Virus as Inguinal Lymphadenopathy

    Directory of Open Access Journals (Sweden)

    Sarah A. Fleming

    2015-01-01

    Full Text Available Genital herpes simplex virus (HSV infections are a common cause of inguinal lymphadenopathy. However, surgical excision of enlarged inguinal nodes is almost never performed to initially diagnose genital herpes simplex virus, due to the distinct external presentation of genital herpetic vesicles that usually occur with the first symptoms of infection. Therefore, the histologic and immunophenotypic features of HSV-associated inguinal lymphadenopathy are unfamiliar to most pathologists. The current report describes the lymph node pathology of two immunocompetent patients, whose initial HSV diagnosis was established through surgical excision of enlarged inguinal lymph nodes. Histologic examination showed features consistent with viral lymphadenopathy, including florid follicular hyperplasia, monocytoid B-cell hyperplasia, and paracortical hyperplasia without extensive necrosis. Immunohistochemical stains for HSV antigens, using polyclonal anti-HSV I and II antibodies, demonstrate strong immunoreactivity for HSV in a small number of cells in the subcapsular sinuses, especially in areas with monocytoid B-cell hyperplasia. Rare scattered HSV-positive cells also are identified in paracortical areas and germinal centers. We conclude that an initial diagnosis of genital HSV infection may be established by inguinal lymph node biopsy.

  18. Empiric acyclovir for neonatal herpes simplex virus infection.

    Science.gov (United States)

    Vanderpluym, Christina; Tawfik, Gerda; Hervas-Malo, Marilou; Lacaze-Masmonteil, Thierry; Kellner, James; Robinson, Joan L

    2012-08-01

    Because neonatal herpes simplex virus (NHSV) infection is difficult to diagnose, there has been a move towards using more empiric acyclovir (ACV). The purpose of this study was to review the use of ACV to optimize future management of NHSV. Charts were reviewed for infants started on intravenous ACV up to day 43 of life--January 2001 through February 2007--at five hospitals in Edmonton and Calgary. ACV was started for possible (N = 115) or proven (N = 3) herpes simplex virus (HSV) infection. Six of the infants with possible HSV infection later had proven HSV infection. Seizures (34%), hemodynamic instability (29%) and skin lesions (24%) were the most common indications for ACV. Among the 118 infants, 106 (90%) had cerebrospinal fluid obtained and 82 (69%) had at least one surface swab for HSV but 4 (3%) had no specimens submitted for HSV detection. ACV was continued for 3.9 ± 3.5 days in the infants with no proven HSV disease. Possible nephrotoxicity from ACV was recorded in 3 of these 109 infants and in none of the infants with proven HSV disease. Clinicians in Alberta primarily consider the diagnosis of NHSV infection when confronted with a neonate with seizures, hemodynamic instability or suspicious skin lesions, but need to consider the diagnosis more often if all cases are to be treated at first presentation. They often perform incomplete investigations to rule out NHSV infection. Adverse events from ACV appear to be uncommon when the drug is used for suspected NHSV disease.

  19. Herpes zoster after autologous hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Kelli Borges dos Santos

    Full Text Available ABSTRACT Background: The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. Methods: A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. Results: Fourteen (6.1% patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3% were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection (p-value = 0.002. There were no significant differences for the other variables analyzed. Conclusion: The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.

  20. Rapid Detection of Herpes Viruses for Clinical Applications

    Science.gov (United States)

    Pierson, Duane; Mehta, Satish

    2013-01-01

    There are eight herpes viruses that infect humans, causing a wide range of diseases resulting in considerable morbidity and associated costs. Varicella zoster virus (VZV) is a human herpes virus that causes chickenpox in children and shingles in adults. Approximately 1,000,000 new cases of shingles occur each year; post-herpetic neuralgia (PHN) follows shingles in 100,000 to 200,000 people annually. PHN is characterized by debilitating, nearly unbearable pain for weeks, months, and even years. The onset of shingles is characterized by pain, followed by the zoster rash, leading to blisters and severe pain. The problem is that in the early stages, shingles can be difficult to diagnose; chickenpox in adults can be equally difficult to diagnose. As a result, both diseases can be misdiagnosed (false positive/negative). A molecular assay has been adapted for use in diagnosing VZV diseases. The polymerase chain reaction (PCR) assay is a non-invasive, rapid, sensitive, and highly specific method for VZV DNA detection. It provides unequivocal results and can effectively end misdiagnoses. This is an approximately two-hour assay that allows unequivocal diagnosis and rapid antiviral drug intervention. It has been demonstrated that rapid intervention can prevent full development of the disease, resulting in reduced likelihood of PHN. The technology was extended to shingles patients and demonstrated that VZV is shed in saliva and blood of all shingles patients. The amount of VZV in saliva parallels the medical outcome.

  1. Herpes simplex virus 1 pneumonia: conventional chest radiograph pattern

    International Nuclear Information System (INIS)

    Umans, U.; Golding, R.P.; Duraku, S.; Manoliu, R.A.

    2001-01-01

    The aim of this study was to describe the findings on plain chest radiographs in patients with herpes simplex virus pneumonia (HSVP). The study was based on 17 patients who at a retrospective search have been found to have a monoinfection with herpes simplex virus. The diagnosis was established by isolation of the virus from material obtained during fiberoptic bronchoscopy (FOB) which also included broncho-alveolar lavage and tissue sampling. Fourteen patients had a chest radiograph performed within 24 h of the date of the FOB. Two radiographs showed no abnormalities of the lung parenchyma. The radiographs of the other 12 patients showed lung opacification, predominantly lobar or more extensive and always bilateral. Most patients presented with a mixed airspace and interstitial pattern of opacities, but 11 of 14 showed at least an airspace consolidation. Lobar, segmental, or subsegmental atelectasis was present in 7 patients, and unilateral or bilateral pleural effusion in 8 patients, but only in 1 patient was it a large amount. In contradiction to the literature which reports a high correlation between HSVP and acute respiratory distress syndrome (ARDS), 11 of 14 patients did not meet the pathophysiological criteria for ARDS. The radiologist may suggest the diagnosis of HSVP when bilateral airspace consolidation or mixed opacities appear in a susceptible group of patients who are not thought to have ARDS or pulmonary edema. The definite diagnosis of HSV pneumonia can be established only on the basis of culture of material obtained by broncho-alveolar lavage. (orig.)

  2. Bioactive natural products with anti-herpes simplex virus properties.

    Science.gov (United States)

    Hassan, Sherif T S; Masarčíková, Radka; Berchová, Kateřina

    2015-10-01

    In this review, we highlight and summarise the most promising extracts, fractions and pure compounds as potential anti-herpes simplex virus (HSV) agents derived from microorganisms, marine organisms, fungi, animals and plants. The role of natural products in the development of anti-HSV drugs will be discussed. Herpes simplex viruses (HSV-1 and -2) are common human pathogens that remain a serious threat to human health. In recent years, a great interest has been devoted to the search for integrated management of HSV infections. Acyclovir and related nucleoside analogues have been licensed for the therapy that target viral DNA polymerase. Although these drugs are currently effective against HSV infections, the intensive use of these drugs has led to the problem of drug-resistant strains. Therefore, the search for new sources to develop new antiherpetic agents has gained major priority to overcome the problem. Natural products as potential, new anti-HSV drugs provide several advantages such as reduced side effects, less resistance, low toxicity and various mechanisms of action. This paper aims to provide an overview of natural products that possess antiviral activity against HSV. © 2015 Royal Pharmaceutical Society.

  3. The molecular basis of herpes simplex virus latency

    Science.gov (United States)

    Nicoll, Michael P; Proença, João T; Efstathiou, Stacey

    2012-01-01

    Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency within sensory neurones. Following primary infection, the virus replicates productively within mucosal epithelial cells and enters sensory neurones via nerve termini. The virus is then transported to neuronal cell bodies where latency can be established. Periodically, the virus can reactivate to resume its normal lytic cycle gene expression programme and result in the generation of new virus progeny that are transported axonally back to the periphery. The ability to establish lifelong latency within the host and to periodically reactivate to facilitate dissemination is central to the survival strategy of this virus. Although incompletely understood, this review will focus on the mechanisms involved in the regulation of latency that centre on the functions of the virus-encoded latency-associated transcripts (LATs), epigenetic regulation of the latent virus genome and the molecular events that precipitate reactivation. This review considers current knowledge and hypotheses relating to the mechanisms involved in the establishment, maintenance and reactivation herpes simplex virus latency. PMID:22150699

  4. Functional interaction between herpes simplex virus type 2 gD and HVEM transiently dampens local chemokine production after murine mucosal infection.

    Directory of Open Access Journals (Sweden)

    Miri Yoon

    2011-01-01

    Full Text Available Herpes virus entry mediator (HVEM is one of two principal receptors mediating herpes simplex virus (HSV entry into murine and human cells. It functions naturally as an immune signaling co-receptor, and may participate in enhancing or repressing immune responses depending on the natural ligand used. To investigate whether engagement of HVEM by HSV affects the in vivo response to HSV infection, we generated recombinants of HSV-2(333 that expressed wild-type gD (HSV-2/gD or mutant gD able to bind to nectin-1 (the other principal entry receptor but not HVEM. Replication kinetics and yields of the recombinant strains on Vero cells were indistinguishable from those of wild-type HSV-2(333. After intravaginal inoculation with mutant or wild-type virus, adult female C57BL/6 mice developed vaginal lesions and mortality in similar proportions, and mucosal viral titers were similar or lower for mutant strains at different times. Relative to HSV-2/gD, percentages of HSV-specific CD8(+ T-cells were similar or only slightly reduced after infection with the mutant strain HSV-2/gD-Δ7-15, in all tissues up to 9 days after infection. Levels of HSV-specific CD4(+ T-cells five days after infection also did not differ after infection with either strain. Levels of the cytokine IL-6 and of the chemokines CXCL9, CXCL10, and CCL4 were significantly lower in vaginal washes one day after infection with HSV-2/gD compared with HSV-2/gD-Δ7-15. We conclude that the interaction of HSV gD with HVEM may alter early innate events in the murine immune response to infection, without significantly affecting acute mortality, morbidity, or initial T-cell responses after lethal challenge.

  5. Diffusion-weighted MR imaging findings in a patient with herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Heiner, L.; Demaerel, Ph.

    2003-01-01

    Introduction: Herpes simplex meningoencephalitis is one of the most common viral central nervous system infection in adults. Early diagnosis is essential for treatment. Case report: We present a case of a 68-year-old female patient with herpes simplex infection. On admission, she was in severe clinical condition. Diffusion-weighted (DW) magnetic resonance imaging detected brain involvement better than conventional sequences. After acyclovir therapy, the patient fully recovered. Conclusion: DW magnetic resonance imaging is expected to provide a more sensitive imaging in herpes simplex patients than conventional sequences

  6. Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

    International Nuclear Information System (INIS)

    Straus, S.E.

    1989-01-01

    The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle the neurons

  7. Herpes Zoster Infections in SLE in a University Hospital in Saudi Arabia: Risk Factors and Outcomes

    Directory of Open Access Journals (Sweden)

    Afsar Sayeeda

    2010-01-01

    (0/23. None of the patients had postherpetic neuralgia or bacterial super infection. Immunosuppressive medications were discontinued at the time of diagnosis of Zoster in 19 of 32 patients and all patients received antiviral medications.There were no permanent neurologic deficits or deaths. We conclude that Herpes Zoster infections occur at increased frequency among patients with SLE and carry significant morbidity. Immunosuppressive therapy and severe manifestations of lupus may be risk factors for the development of Herpes Zoster although not necessarily at the time of disease flare or immunosuppressive therapy. Our study suggests that although Herpes Zoster occurs frequently in patients with SLE, it has a relatively benign course.

  8. Controlled Release from Recombinant Polymers

    Science.gov (United States)

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-01-01

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

  9. Hydrogen recombiner development at AECL

    International Nuclear Information System (INIS)

    Dewit, W.A.; Koroll, G.W.; Loesel Sitar, J.; Graham, W.R.C.

    1997-01-01

    Catalytic recombiners have been developed at AECL for the purpose of hydrogen removal in post-accident nuclear containment buildings. The recombiners are based on a particular catalyst designed by AECL which has extraordinary resistance to fouling from water and water vapour and a large thermodynamic range of operation. The catalysts were developed, originally, for the purpose of heavy water manufacturing by way of a catalytic exchange process. Application of these catalyst materials in recombiners for containment applications began in the late 1980's. The first application was a passive recombiner, qualified for use in control of radiolytic hydrogen in the headspace of a pool-type experimental reactor of AECL design in 1988. The passive, or natural convection recombiner concept has continued development to commercial stage for application in power reactor containments. This paper reviews the AECL recombiner development, describes the current model and shows results from tests of full-scale recombiners in the Large Scale Vented Combustion Test Facility at AECL-WL. The AECL recombiner is designed for compactness and ease of engineering into containment. The design is a simple, open-ended rectangular enclosure with catalyst elements arranged inside to promote optimum convective flow driven by heat of recombination at the catalyst surface. Self start, as evidenced by catalyst heating and initiation of flow, is achieved in less than 1% hydrogen, with available oxygen, at room temperature and 100% relative humidity. This low temperature start-up in condensing atmospheres is viewed as the most challenging condition for wet-proofing effectiveness. Cold start-up is a vital performance requirement in containments, such as CANDU, where engineered air-cooling systems are operating and where long-term hydrogen control is required, after containment atmospheres have cooled. Once started, the removal capacity scales linearly with the inlet cross-section area and the partial

  10. Review of Parton Recombination Models

    International Nuclear Information System (INIS)

    Bass, Steffen A

    2006-01-01

    Parton recombination models have been very successful in explaining data taken at RHIC on hadron spectra and emission patterns in Au+Au collisions at transverse momenta above 2 GeV/c, which have exhibited features which could not be understood in the framework of basic perturbative QCD. In this article I will review the current status on recombination models and outline which future challenges need to be addressed by this class of models

  11. Recombinant snake venom prothrombin activators

    OpenAIRE

    L?vgren, Ann

    2012-01-01

    Three prothrombin activators; ecarin, which was originally isolated from the venom of the saw-scaled viper Echis carinatus, trocarin from the rough-scaled snake Tropidechis carinatus, and oscutarin from the Taipan snake Oxyuranus scutellatus, were expressed in mammalian cells with the purpose to obtain recombinant prothrombin activators that could be used to convert prothrombin to thrombin. We have previously reported that recombinant ecarin can efficiently generate thrombin without the need ...

  12. Potential risk of developing herpes simplex encephalitis in patients treated with sildenafil following primary exposure to genital herpes.

    Science.gov (United States)

    Goren, A; Mccoy, J; Kovacevic, M; Situm, M; Lonky, N

    2017-01-01

    Herpes simplex encephalitis (HSE) is associated with significant mortality and morbidity. As a consequence of HSE, up to 75% of infected individuals die or experience irreversible neurological damage. While the pathogenesis of the disease is unknown, it is traditionally hypothesized that the viral infection occurs by neuronal transmission directly from peripheral sites. Non-neuronal modes of infection have generally been overlooked as the brain is protected by the blood-brain-barrier (BBB). The BBB poses an effective barrier to pathogens as well as to drugs such as chemotherapies. In the pursuit to deliver chemotherapeutic agents to the brain, several studies demonstrated that phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may increase the permeability of the BBB enabling successful delivery of chemotherapeutic agents to the brain. In this communication, we report a case of HSE infection in a 62-year-old man, which we suspect was facilitated by the use of sildenafil during a primary genital herpes simple virus (HSV) infection. Due to large number of patients treated with PDE5 inhibitors for erectile dysfunction and the high incidence of genital HSV infection in the general population, a larger study should examine the potential risk of developing HSE in patients treated with PDE5 inhibitors.

  13. Immunization against Genital Herpes with a Vaccine Virus That has Defects in Productive and Latent Infection

    Science.gov (United States)

    da Costa, Xavier J.; Jones, Cheryl A.; Knipe, David M.

    1999-06-01

    An effective vaccine for genital herpes has been difficult to achieve because of the limited efficacy of subunit vaccines and the safety concerns about live viruses. As an alternative approach, mutant herpes simplex virus strains that are replication-defective can induce protective immunity. To increase the level of safety and to prove that replication was not needed for immunization, we constructed a mutant herpes simplex virus 2 strain containing two deletion mutations, each of which eliminated viral replication. The double-mutant virus induces protective immunity that can reduce acute viral shedding and latent infection in a mouse genital model, but importantly, the double-mutant virus shows a phenotypic defect in latent infection. This herpes vaccine strain, which is immunogenic but has defects in both productive and latent infection, provides a paradigm for the design of vaccines and vaccine vectors for other sexually transmitted diseases, such as AIDS.

  14. Disseminated herpes zoster ophthalmicus in an immunocompetent 8-year old boy

    Directory of Open Access Journals (Sweden)

    Regina Eziuka Oladokun

    2013-05-01

    Full Text Available Varicella results from a primary infection with the varicella virus while herpes zoster is caused by a reactivation of a latent infection. Dissemination of herpes zoster is uncommon in immunocompetent individuals. Reports of disseminated herpes zoster in children are even less common than in adults. An unusual case of disseminated herpes zoster ophthalmicus in an 8-year old immunocompetent black boy is presented. He had a previous primary Varicella zoster virus infection at three years of age. In the current report, he presented during an on-going chicken pox outbreak and survived with no significant complications. A breakthrough varicella virus re-infection or a reactivation is possible, both of which could present as zoster. This case emphasizes the need for prevention of varicella virus infection through universal childhood immunization and effective infection control strategies in health care settings.

  15. A Fusogenic Oncolytic Herpes Simplex Virus for Therapy of Advanced Ovarian Cancer

    National Research Council Canada - National Science Library

    Zhang, Xiaoliu

    2004-01-01

    The tasks that were originally planned for the first year of this 3 year project are to demonstrate that the fusogenic oncolytic herpes simplex viruses are potent anti-tumor agents for advanced ovarian cancer...

  16. Molecular Characterization of Prostate Cancer Cell Oncolysis by Herpes Simplex Virus ICP0 Mutants

    National Research Council Canada - National Science Library

    Mossman, Karen

    2005-01-01

    .... Briefly, the goals of the proposal were to characterize the oncolytic capacity of Herpes simplex virus type 1 ICPO mutants in prostate cancer cells given the relationship between ICPO and two tumor...

  17. Molecular Characterization of Prostate Cancer Cell Oncolysis by Herpes Simplex Virus ICP0 Mutants

    National Research Council Canada - National Science Library

    Mossman, Karen

    2006-01-01

    .... Briefly, the goals of the proposal were to characterize the oncolytic capacity of Herpes simplex virus type 1 ICP0 mutants in prostate cancer cells given the relationship between ICP0 and two tumor...

  18. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    International Nuclear Information System (INIS)

    Perna, J.J.; Mannix, M.L.; Rooney, J.F.; Notkins, A.L.; Straus, S.E.

    1987-01-01

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation

  19. Adenovirus, herpes simplex virus and cytomegalovirus infection in a lung transplant recipient

    Directory of Open Access Journals (Sweden)

    Sandhya Nagarakanti

    2018-01-01

    Full Text Available Allograft infections post lung transplantation have a significant impact on morbidity and mortality. We report a rare case of triple viral infection with adenovirus, Herpes Simplex virus (HSV and Cytomegalovirus (CMV in a lung transplant recipient.

  20. HIV-associated fulminating herpes zoster infection with alveolar necrosis and tooth exfoliation: a case report.

    Science.gov (United States)

    Chindia, M L

    1997-04-01

    This paper presents a case of HIV-associated fulminating herpes zoster infection (HZI) that culminated in right mandibular necrosis and tooth exfoliation. The occurrence of such infection in immunosuppression and the impending clinical features are briefly reviewed and discussed.

  1. Residues of the UL25 Protein of Herpes Simplex Virus That Are Required for Its Stable Interaction with Capsids ▿

    Science.gov (United States)

    Cockrell, Shelley K.; Huffman, Jamie B.; Toropova, Katerina; Conway, James F.; Homa, Fred L.

    2011-01-01

    The herpes simplex virus 1 (HSV-1) UL25 gene product is a minor capsid component that is required for encapsidation, but not cleavage, of replicated viral DNA. UL25 is located on the capsid surface in a proposed heterodimer with UL17, where five copies of the heterodimer are found at each of the capsid vertices. Previously, we demonstrated that amino acids 1 to 50 of UL25 are essential for its stable interaction with capsids. To further define the UL25 capsid binding domain, we generated recombinant viruses with either small truncations or amino acid substitutions in the UL25 N terminus. Studies of these mutants demonstrated that there are two important regions within the capsid binding domain. The first 27 amino acids are essential for capsid binding of UL25, while residues 26 to 39, which are highly conserved in the UL25 homologues of other alphaherpesviruses, were found to be critical for stable capsid binding. Cryo-electron microscopy reconstructions of capsids containing either a small tag on the N terminus of UL25 or the green fluorescent protein (GFP) fused between amino acids 50 and 51 of UL25 demonstrate that residues 1 to 27 of UL25 contact the hexon adjacent to the penton. A second region, most likely centered on amino acids 26 to 39, contacts the triplex that is one removed from the penton. Importantly, both of these UL25 capsid binding regions are essential for the stable packaging of full-length viral genomes. PMID:21411517

  2. Herpes Virus Entry Mediator Signaling in the Brain Is Imperative in Acute Inflammation-Induced Anorexia and Body Weight Loss

    Directory of Open Access Journals (Sweden)

    Kwang Kon Kim

    2013-09-01

    Full Text Available BackgroundReduced appetite and body weight loss are typical symptoms of inflammatory diseases. A number of inflammatory stimuli are responsible for the imbalance in energy homeostasis, leading to metabolic disorders. The herpes virus entry mediator (HVEM protein plays an important role in the development of various inflammatory diseases, such as intestinal inflammation and diet-induced obesity. However, the role of HVEM in the brain is largely unknown. This study aims to investigate whether HVEM signaling in the brain is involved in inflammation-induced anorexia and body weight loss.MethodsFood intake and body weight were measured at 24 hours after intraperitoneal injection of lipopolysaccharide (LPS or intracerebroventricular injection of recombinant mouse LIGHT (also called tumor necrosis factor receptor superfamily 14, TNFSF14, an HVEM ligand, into 8- to 10-week-old male C57BL/6 mice and mice lacking HVEM expression (HVEM-/-. We also assessed LPS-induced change in hypothalamic expression of HVEM using immunohistochemistry.ResultsAdministration of LPS significantly reduced food intake and body weight, and moreover, increased expression of HVEM in the hypothalamic arcuate nucleus. However, LPS induced only minor decreases in food intake and body weight in HVEM-/- mice. Administration of LIGHT into the brain was very effective at decreasing food intake and body weight in wild-type mice, but was less effective in HVEM-/- mice.ConclusionActivation of brain HVEM signaling is responsible for inflammation-induced anorexia and body weight loss.

  3. Risk factors for herpes simplex virus type 2 infection among female commercial sex workers in Mexico City.

    Science.gov (United States)

    Uribe-Salas, F; Hernández-Avila, M; Juárez-Figueroa, L; Conde-Glez, C J; Uribe-Zúñiga, P

    1999-02-01

    A scarce number of studies have been carried out to determine the epidemiology of herpes simplex virus type 2 (HSV-2) infection in female sex workers (FSWs). The objective of this study was to examine the correlates of infection for HSV-2 with socioeconomic and demographic characteristics, sexual behaviour and history of sexually transmitted diseases (STDs) among FSWs in Mexico City. A sample frame of commercial sex work sites was constructed during the fall of 1992. Sites identified were streets, bars and massage parlours. During 1993 we surveyed 757 FSWs aged 18-76 years, from a random sample of sites. Participating women provided a blood sample and answered a standardized questionnaire. HSV-2 antibodies were identified based on a Western blot assay, using type-specific recombinant glycoprotein gG2. In a multivariate analysis, the presence of HSV-2 antibodies was correlated (P prostitutes, low education, street working site and positive serology for syphilis. The results showed that the working site and the education level are contextual variables related to the risk of HSV-2 infection, where poorly educated and street FSWs had the highest probability of infection. Characteristics that represent periods of exposure to the virus as age and time working in prostitution were predictors of the HSV-2 infection.

  4. Herpes Zoster Lesions on Reconstructed Breast Skin: Rare Objective Proof of Reinervation

    Directory of Open Access Journals (Sweden)

    Laurenz Weitgasser

    2017-01-01

    Full Text Available Blazed up Herpes zoster lesions have been described in very few patients after free and pedicled flap transfer for reconstructive purpose. Although sensory recovery after flap reconstructions has been studied extensively most studies addressed subjective perceptions of sensation. Objective investigations of spontaneous reinervation of free and pedicled flaps are rare. We would like to present a witnessed herpes zoster infection of a latissimus dorsi skin flap 2 years after breast reconstruction.

  5. Atypical oral presentation of herpes simplex virus infection in a patient after orthotopic liver transplantation.

    Science.gov (United States)

    Burke, E M; Karp, D L; Wu, T C; Corio, R L

    1994-01-01

    An atypical oral presentation of herpes simplex virus infection in a 49-year-old woman after orthotopic liver transplantation is reported. Clinically, the differential diagnosis included chronic hyperplastic candidiasis, nodular leukoplakia of undetermined etiology, and malignant neoplasm. An excisional biopsy revealed herpesvirus infection, and immunoperoxidase staining confirmed herpes simplex virus infection. This report describes the clinical and histologic appearance of these lesions and the course and treatment of the patient.

  6. Occurrence of herpes zoster varicella infections after completion of treatment for Hodgkin's disease

    International Nuclear Information System (INIS)

    Pauw, B.E. de; Janssen, J.Th.P.; Vaissier, P.; Haanen, C.

    1983-01-01

    Retrospective analysis of 210 cases of patients with Hodgkin's disease revealed an overall incidence of herpes zoster varicella of 9.5 per cent. Patients with the mixed cellular histological subtype showed a significantly increased (p < 0.05) risk as compared with the total population. More than 90 per cent of the herpes zoster varicella infections occurred after termination of treatment; a combination of radiotherapy with chemotherapy proved to be a predisposing factor. (Auth.)

  7. A rare case of Herpes zoster oticus in an immunocompetent patient

    Directory of Open Access Journals (Sweden)

    Ganesh Prabhakar Dhavalshankh

    2012-10-01

    Full Text Available Herpes zoster oticus in healthy persons is uncommon, though it has been described in immunocompromised patients. We describe a case of disseminated herpes zoster oticus in an elderly man with no apparent immunosuppressive condition. The patient was treated successfully with oral Acyclovir. We suggest that disseminated zoster can occur in an immunocompetent host and should be promptly recognized and treated to prevent serious complications.

  8. Herpes simplex virus type 2: Cluster of unrelated cases in an intensive care unit.

    Science.gov (United States)

    Troché, Gilles; Marque Juillet, Stephanie; Burrel, Sonia; Boutolleau, David; Bédos, Jean-Pierre; Legriel, Stephane

    2016-10-01

    Herpes simplex viruses, which are associated with various clinical manifestations, can be transmitted to critically ill patients from other patients or health care staff. We report an apparent outbreak of mucocutaneous herpes simplex virus 2 infections (5 cases in 10 weeks). An epidemiologic investigation and genotype analysis showed no connections among the 5 cases. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  9. Computational Studies of Benzoxazinone Derivatives as Antiviral Agents against Herpes Virus Type 1 Protease

    OpenAIRE

    Mello, Juliana; Botelho, Nathália; Souza, Alessandra; Oliveira, Riethe; Brito, Monique; Abrahim-Vieira, Bárbara; Sodero, Ana; Castro, Helena; Cabral, Lucio; Miceli, Leonardo; Rodrigues, Carlos

    2015-01-01

    Herpes simplex virus infections have been described in the medical literature for centuries, yet the the drugs available nowadays for therapy are largely ineffective and low oral bioavailability plays an important role on the inefficacy of the treatments. Additionally, the details of the inhibition of Herpes Virus type 1 are still not fully understood. Studies have shown that several viruses encode one or more proteases required for the production new infectious virions. This study presents a...

  10. Cesarean Delivery in Women With Genital Herpes in Washington State, 1989–1991

    OpenAIRE

    Marrazzo, Jeanne M.; John, Grace C.; Krohn, Marijane A.; Corey, Lawrence

    1997-01-01

    Objective: The purpose of this study was to determine whether the proportion of cesarean deliveries in pregnant women with a history of genital herpes and no active lesions at birth is higher than that in women with no history of genital herpes, and to determine whether this risk was modified by birth facilities' underlying prevalence of cesarean delivery. Methods: This was a retrospective survey. Women who gave birth in Washington state from 1989 to 1991 were identified from the state birth ...

  11. Acute encephalomyelitis with multiple herpes viral reactivations during abatacept therapy.

    Science.gov (United States)

    Nakajima, Hideto; Takayama, Ayami; Ito, Takumi; Yoshikawa, Tetsushi

    2013-05-09

    To describe the case of a patient who had been receiving abatacept, a T-cell costimulatory molecule blocker for rheumatoid arthritis, and developed an acute encephalomyelitis associated with reactivation of the varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). A 61-year-old woman receiving abatacept therapy for rheumatoid arthritis developed a disturbance of consciousness. MRI indicated multifocal parenchymal lesions in the brainstem, supratentorial areas and cervical spinal cord. Although steroid therapy significantly improved the neurological symptoms and MRI findings, the patient died of sepsis aggravated by coinfection with a fungal infection. Retrospectively, a PCR assay revealed continued systemic reactivation of VZV, EBV and CMV. Acute encephalomyelitis may be associated with VZV EBV and CMV reactivation during abatacept therapy. Clinicians must be aware of the possibility of acute encephalomyelitis associated with herpes virus reactivation during abatacept therapy for rheumatoid arthritis.

  12. Herpes simplex virus 1 induces de novo phospholipid synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Sutter, Esther [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Oliveira, Anna Paula de; Tobler, Kurt [Electron microscopy, Institute of Virology, University of Zuerich (Switzerland); Schraner, Elisabeth M. [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland); Sonda, Sabrina [Institute of Parasitology, University of Zuerich (Switzerland); Kaech, Andres [Center for Microscopy and Image Analysis, University of Zuerich (Switzerland); Lucas, Miriam S. [Electron Microscopy ETH Zuerich (EMEZ), Swiss Federal Institute of Technology, Zuerich (Switzerland); Ackermann, Mathias [Electron microscopy, Institute of Virology, University of Zuerich (Switzerland); Wild, Peter, E-mail: pewild@access.uzh.ch [Electron Microscopy, Institute of Veterinary Anatomy, University of Zuerich (Switzerland)

    2012-08-01

    Herpes simplex virus type 1 capsids bud at nuclear membranes and Golgi membranes acquiring an envelope composed of phospholipids. Hence, we measured incorporation of phospholipid precursors into these membranes, and quantified changes in size of cellular compartments by morphometric analysis. Incorporation of [{sup 3}H]-choline into both nuclear and cytoplasmic membranes was significantly enhanced upon infection. [{sup 3}H]-choline was also part of isolated virions even grown in the presence of brefeldin A. Nuclei expanded early in infection. The Golgi complex and vacuoles increased substantially whereas the endoplasmic reticulum enlarged only temporarily. The data suggest that HSV-1 stimulates phospholipid synthesis, and that de novo synthesized phospholipids are inserted into nuclear and cytoplasmic membranes to i) maintain membrane integrity in the course of nuclear and cellular expansion, ii) to supply membrane constituents for envelopment of capsids by budding at nuclear membranes and Golgi membranes, and iii) to provide membranes for formation of transport vacuoles.

  13. [Role of Herpes simplex virus in the immune stromal keratitis].

    Science.gov (United States)

    Vinagre, C; Martínez, M J; Vogel, M; Traipe, L; Stoppel, J; Squella, O; Srur, M; Charlín, R

    2001-03-01

    Herpes simplex virus (HSV) infection of the cornea is a leading cause of blindness in occidental countries and a common recurrent manifestation of it is the immune stromal keratitis (ISK). However, it is not known whether active viral replication occurs during the acute phase of the disease, because isolation of the virus by conventional culture techniques has not been accomplished. To establish the presence of HSV in patients with ISK. Fourteen corneal swabbing samples, from active diseased eyes of patients with clinical diagnosis of ISK, were submitted to Herpchek and PCR for the identification of HSV antigens and genome. All ISK samples were negative by both techniques. It was not possible to identify HSV antigens nor their genome by the methodology used. It is likely that, they can't be detected in corneal superficial layers or probably there is no viral replication at this stage of the disease, so antiviral therapy should be reconsidered.

  14. Lytic Promoters Express Protein during Herpes Simplex Virus Latency

    Science.gov (United States)

    Russell, Tiffany A.; Tscharke, David C.

    2016-01-01

    Herpes simplex virus (HSV) has provided the prototype for viral latency with previously well-defined acute or lytic and latent phases. More recently, the deep quiescence of HSV latency has been questioned with evidence that lytic genes can be transcribed in this state. However, to date the only evidence that these transcripts might be translated has come from immunological studies that show activated T cells persist in the nervous system during latency. Here we use a highly sensitive Cre-marking model to show that lytic and latent phases are less clearly defined in two significant ways. First, around half of the HSV spread leading to latently infected sites occurred beyond the initial acute infection and second, we show direct evidence that lytic promoters can drive protein expression during latency. PMID:27348812

  15. Herpes zoster ophthalmicus with associated vasculopathy causing stroke.

    Science.gov (United States)

    Antia, Camila; Persad, Leah; Alikhan, Ali

    2017-07-15

    Varicella zoster virus (VZV) is an exclusively human, double-stranded DNA virus. Primary infection causes varicella (chickenpox); later the virus becomes dormant in the dorsal root, cranial nerve, and autonomic ganglia along the entire span of the nervous system, retaining the capacity to reactivate and cause a variety of dermal and neurological complications. Recently there has been increasing recognition, both clinically and epidemiologically, of the relationship between VZV and subsequent strokes. Herein, we describe a case of a previously healthy individual with reactivation of VZV causing herpes zoster opthtalmicus along with devastating multifocal vasculopathy. It is crucial for dermatologists to recognize the dermatomal vesicular eruption in this high risk area to aid in prompt diagnosis in an effort to improve clinical prognosis.

  16. Herpes zoster in breast cancer patients after radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dunst, J.; Steil, B.; Furch, S.; Fach, A. [Halle-Wittenberg Univ., Halle (Germany). Dept. of Radiotherapy; Bormann, G.; Marsch, W. [Halle-Wittenberg Univ., Halle (Germany). Dept. of Dermatology

    2000-11-01

    Purpose: We have studied the incidence of herpes zoster in patients with adjuvant radiotherapy for breast cancer with special emphasis on possible correlations with other prognostic factors or survival. Patients and Methods: From 1/1985 through 12/1993, 1 155 breast cancer patients received postoperative radiotherapy with curative intent in our department. After mastectomy 961 patients were irradiated and after breast-preserving treatment 194 patients. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3 to 12.4 years). There were 443 women (38%) pre- and 712 (62%) postmenopausal. 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. In case of postmastectomy radiotherapy, the lateral chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field to 50 Gy (axilla 44 Gy) and most of the chest wall with an electron field to 44 Gy in 2-Gy fractions. After breast-preservation, the breast was irradiated via tangential fields with 6- to 8-MV photons up to 50 Gy plus 8 Gy electron boost to the tumor bed. Most of the patients were followed routinely in the department for 2 to 5 years. The frequency of zoster was determined retrospectively by reviewing the patients' records. Results: A zoster after radiotherapy occurred in 41/1 155 patients (3.7%), mostly within the first 2 years after completion of radiotherapy. All infections remained localized and there was no evidence for systemic infections. Type of treatment (mastectomy vs breast-preservation) had no impact on the frequency of herpes zoster (36/961 patients after mastectomy and 5/194 patients after breast-preservation). There was also no correlation with other prognostic factors such as age, menopausal status, stage of disease or the use of adjuvant chemotherapy, nor was the occurrence of zoster linked to the degree of acute skin reaction in

  17. Herpes Zoster in a 3-month-old infant

    Directory of Open Access Journals (Sweden)

    Duarte Malveiro

    2015-12-01

    Full Text Available Introduction: Herpes Zoster (HZ is rare in infancy and results from reactivation of varicella-zoster virus, latent in the dorsal root ganglia of sensory or cranial nerves after primary infection (chickenpox. Case Report: We describe the case of an healthy infant, three months old, without previous clinical symptoms of chickenpox, in spite of having contacted with the disease at two weeks of life. She was hospitalized for vesicular-papular rash involving unilaterally dermatomes L4 and L5 and was treated with acyclovir with good clinical outcome. Conclusion: The immaturity of the immune system and the interference of maternal antibodies contribute to the manifestation of HZ in the first year of life. In a previously healthy child it is not recommended the exclusion of underlying immunodeficiency or malignant disease.

  18. Understanding perceptions of genital herpes disclosure through analysis of an online video contest.

    Science.gov (United States)

    Catallozzi, Marina; Ebel, Sophia C; Chávez, Noé R; Shearer, Lee S; Mindel, Adrian; Rosenthal, Susan L

    2013-12-01

    The aims of this study were to examine pre-existing videos in order to explore the motivation for, possible approaches to, and timing and context of disclosure of genital herpes infection as described by the lay public. A thematic content analysis was performed on 63 videos submitted to an Australian online contest sponsored by the Australian Herpes Management Forum and Novartis Pharmaceuticals designed to promote disclosure of genital herpes. Videos either provided a motivation for disclosure of genital herpes or directed disclosure without an explicit rationale. Motivations included manageability of the disease or consistency with important values. Evaluation of strategies and logistics of disclosure revealed a variety of communication styles including direct and indirect. Disclosure settings included those that were private, semiprivate and public. Disclosure was portrayed in a variety of relationship types, and at different times within those relationships, with many videos demonstrating disclosure in connection with a romantic setting. Individuals with genital herpes are expected to disclose to susceptible partners. This analysis suggests that understanding lay perspectives on herpes disclosure to a partner may help healthcare providers develop counselling messages that decrease anxiety and foster disclosure to prevent transmission.

  19. Attitudes and Willingness to Assume Risk of Experimental Therapy to Eradicate Genital Herpes Simplex Virus Infection.

    Science.gov (United States)

    Oseso, Linda; Magaret, Amalia S; Jerome, Keith R; Fox, Julie; Wald, Anna

    2016-09-01

    Current treatment of genital herpes is focused on ameliorating signs and symptoms but is not curative. However, as potential herpes simplex virus (HSV) cure approaches are tested in the laboratory, we aimed to assess the interest in such studies by persons with genital herpes and the willingness to assume risks associated with experimental therapy. We constructed an anonymous online questionnaire that was posted on websites that provide information regarding genital herpes. The questions collected demographic and clinical information on adults who self-reported as having genital herpes, and assessed attitudes toward and willingness to participate in HSV cure clinical research. Seven hundred eleven participants provided sufficient responses to be included in the analysis. Sixty-six percent were women; the median age was 37 years, and the median time since genital HSV diagnosis was 4.7 years. The willingness to participate in trials increased from 59.0% in phase 1 to 68.5% in phase 2, and 81.2% in phase 3 trials, and 40% reported willingness to participate even in the absence of immediate, personal benefits. The most desirable outcome was the elimination of risk for transmission to sex partner or neonate. The mean perceived severity of receiving a diagnosis of genital HSV-2 was 4.2 on a scale of 1 to 5. Despite suppressive therapy available, persons with genital herpes are interested in participating in clinical research aimed at curing HSV, especially in more advanced stages of development.

  20. Can a multimedia educational computer-based program on genital herpes teach patients about their disease?

    Science.gov (United States)

    Wald; Stern; Skinner; Beutner; Conant; Tyring; Reitano; Davis

    1998-07-01

    Objective: Education of patients with genital herpes about their disease is time consuming. To evaluate the effectiveness of an educational computer program, we developed a multimedia interactive presentation to teach patients about genital herpes. Such programs can supplement clinician visits for patients with genital herpes, or those at risk for HSV acquisition.Methods: Patients seeking care for genital herpes, or those at risk for HSV acquisition, were asked to participate in the program during routine clinic visits at 5 physician's offices nationwide. A self-administered 7 item herpes knowledge questionnaire was given before and after participation. An additional questionnaire evaluating the satisfaction with the program was also self-administered at completion.Results: 428 patients were enrolled and completed the pre- and post-knowledge questionnaire and 332 patients completed the satisfaction survey. On the pre-test, 20.1% of patients answered all questions correctly, 65.4% answered correctly 4 to 6 questions, and 14.5% 3 or less. On the post-test, 32.9% of patients answered all questions correctly, 61.5% answered correctly 4 to 6 questions, and 5.6% 3 or less (P poor) to 7 (excellent).Conclusion: Computer-based education programs about genital herpes may provide a useful adjunct to teaching in physician offices and result in knowledge gain about the disease, at least short-term. Such programs may assist in management of chronic sexually transmitted infections.

  1. Usefulness of Herpes Consensus PCR methodology to routine diagnostic testing for herpesviruses infections in clinical specimens

    Directory of Open Access Journals (Sweden)

    Priavali Efthalia

    2007-06-01

    Full Text Available Abstract The purposes of the study were to assess the usefulness of simultaneously amplifying herpes simplex virus 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus and human herpesvirus 6 DNA in various clinical specimens and to analyze clinical events in patients presenting positive results. A total of 763 clinical samples obtained from 758 patients, including 115 cerebrospinal fluids, 102 aqueous fluids, 445 swabs from genital (152, oro-facial (138 and other (155 skin lesions, 96 eye swabs and 5 bronchoalveolar lavages, were tested by using the Consensus polymerase chain reaction methodology. The clinical files of the patients were consulted retrospectively. 171 of the 758 patients (22.5% were positive for at least one of the six target viruses: herpes simplex virus 1 (n = 95, varicella-zoster virus (n = 40, herpes simplex virus 2 (n = 21, herpes simplex virus 1 plus herpes simplex virus 2 (n = 8, cytomegalovirus (n = 4, Epstein-Barr virus (n = 1, human herpesvirus 6 (n = 1, and herpes simplex virus 1 plus human herpesvirus 6 (n = 1. The Consensus methodology enabled the rapid and accurate detection of herpesviruses in various clinical specimens and provided a reliable tool in the diagnosis of herpetic infections.

  2. Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.

    Science.gov (United States)

    Jastrzebski, Andre; Brownstein, Seymour; Ziai, Setareh; Saleh, Solin; Lam, Kay; Jackson, W Bruce

    2017-06-01

    We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). Retrospective case report. A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.

  3. Isolation of a new herpes virus from human CD4+ T cells

    International Nuclear Information System (INIS)

    Frenkel, N.; Schirmer, E.C.; Wyatt, L.S.; Katsafanas, G.; Roffman, E.; Danovich, R.M.; June, C.H.

    1990-01-01

    A new human herpes virus has been isolated from CD4 + T cells purified from peripheral blood mononuclear cells of a healthy individual (RK), following incubation of the cells under conditions promoting T-cell activation. The virus could not be recovered from nonactivated cells. Cultures of lymphocytes infected with the RK virus exhibited a cytopathic effect, and electron microscopic analyses revealed a characteristic herpes virus structure. RK virus DNA did not hybridize with large probes derived from herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, and human cytomegalovirus. The genetic relatedness of the RK virus to the recently identified T-lymphotropic human herpes virus 6 (HHV-6) was investigated by restriction enzyme analyses using 21 different enzymes and by blot hydridization analyses using 11 probes derived from two strains of HHV-6 (Z29 and U1102). Whereas the two HHV-6 strains exhibited only limited restriction enzyme polymorphism, cleavage of the RK virus DNA yielded distinct patterns. Of the 11 HHV-6 DNA probes tested, only 6 cross-hybridized with DNA fragments derived from the RK virus. Taken together, the maximal homology amounted to 31 kilobases of the 75 kilobases tested. The authors conclude that the RK virus is distinct from previously characterized human herpesviruses. The authors propose to designate it as the prototype of a new herpes virus, the seventh human herpes virus identified to date

  4. Prediction of conserved sites and domains in glycoproteins B, C and D of herpes viruses.

    Science.gov (United States)

    Rasheed, Muhammad Asif; Ansari, Abdur Rahman; Ihsan, Awais; Navid, Muhammad Tariq; Ur-Rehman, Shahid; Raza, Sohail

    2018-03-01

    Glycoprotein B (gB), C (gC) and D (gD) of herpes simplex virus are implicated in virus adsorption and penetration. The gB, gC and gD are glycoproteins for different processes of virus binding and attachment to the host cells. Moreover, their expression is necessary and sufficient to induce cell fusion in the absence of other glycoproteins. Egress of herpes simplex virus (HSV) and other herpes viruses from cells involves extensive modification of cellular membranes and sequential envelopment, de-envelopment and re-envelopment steps. Viral glycoproteins are important in these processes, and frequently two or more glycoproteins can largely suffice in any step. Hence, we target the 3 important glycoproteins (B, C and D) of eight different herpes viruses of different species. These species include human (HSV1 and 2), bovine (BHV1), equine (EHV1 and 4), chicken (ILT1 and MDV2) and pig (PRV1). By applying different bioinformatics tools, we highlighted the conserved sites in these glycoproteins which might be most significant regarding attachment and infection of the viruses. Moreover the conserved domains in these glycoproteins are also highlighted. From this study, we will able to analyze the role of different viral glycoproteins of different species during herpes virus adsorption and penetration. Moreover, this study will help to construct the antivirals that target the glycoproteins of different herpes viruses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Ras signaling influences permissiveness of malignant peripheral nerve sheath tumor cells to oncolytic herpes.

    Science.gov (United States)

    Farassati, Faris; Pan, Weihong; Yamoutpour, Farnaz; Henke, Susann; Piedra, Mark; Frahm, Silke; Al-Tawil, Said; Mangrum, Wells I; Parada, Luis F; Rabkin, Samuel D; Martuza, Robert L; Kurtz, Andreas

    2008-12-01

    Lack of expression of neurofibromin in neurofibromatosis 1 and its lethal derivative, malignant peripheral nerve sheath tumors (MPNSTs), is thought to result in the overactivation of the Ras signaling pathway. Our previous studies have shown that cells with overactivation in the Ras pathway are more permissive to infection with herpes simplex virus 1 and its mutant version R3616. In this study, we show that among five different mouse MPNST cell lines, only the ones with elevated levels of Ras signaling are highly permissive to infection with oncolytic herpes G207. Specific inhibitors of the Ras, ERK, and JNK pathways all reduced the synthesis of viral proteins in MPNST cells. The cell lines that contained lower levels of Ras and decreased activation of downstream signaling components underwent an enhancement in apoptosis upon exposure to G207. Additionally, mouse SW10 Schwann cells were able to become infected by parental herpes but were found to be resistant to G207. The immortalization of these cell lines with the expression of SV40 large T antigen increased the levels of Ras activation and permissiveness to oncolytic herpes. A Ras/Raf kinase inhibitor reduced the synthesis of both herpes simplex virus-1 and G207 proteins in SW10 cells. The results of this study, therefore, introduce Ras signaling as a divergent turning point for the response of MPNST cells to an assault by oncolytic herpes.

  6. [Herpes Zoster and post-herpetic neuralgia: everything to revise?].

    Science.gov (United States)

    Pasqualucci, A

    1999-01-01

    The treatment and prevention of the algic symptomatology of Post-Herpetic Neuralgia (PHN) are problems still to be solved. In our opinion the reason of this failure is to be found in an insufficient knowledge of the pathophysiological phenomena which cause the PHN. In fact, many fundamental aspects, such as its "temporal" and symptomatological definition and its pathogenesis are still unsolved. This revision tries to focus the problems and discrepancies hindering an improvement in PHN treatment and prevention. The literature reports three different symptomatological levels after herpes zoster acute phase: patients affected by pain and/or allodynia, patients with "abnormal sensations" (anesthesia, paresthesia, dysesthesia, prickling, itching, burning, etc.,) and patients in "complete recovery". Only two studies have analyzed the final incidence of these symptomatologies. Therefore, it is absolutely unclear whether the patients in "abnormal sensations", that is with a symptomatology which is definitely less weakening than pain, have to be considered in PHN (patients with pain) or in "complete recovery". On the contrary, from a clinical and physiopathological point of view this symptomatological difference may have a great importance: the symptomatological non-distinction could be the cause of the disagreement concerning PHN incidence data; this distinction could differentiate and compare in a reliable way the effects of the various therapies reported in the literature. The lack of a symptomatological classification does not facilitate a verification of the physiopathological hypothesis of PHN onset and maintenance. The differentiation among pain, "abnormal sensations" and "complete recovery" could correlate these three symptomatological conditions to the anatomopathological and viral data which according to literature characterize the evolution of Herpes Zoster acute phase in PHN. This would largely help to improve the therapeutic strategy.

  7. Herpes Simplex Virus 1 Interaction with Myeloid Cells In Vivo.

    Science.gov (United States)

    Shivkumar, Maitreyi; Lawler, Clara; Milho, Ricardo; Stevenson, Philip G

    2016-10-01

    Herpes simplex virus 1 (HSV-1) enters mice via olfactory epithelial cells and then colonizes the trigeminal ganglia (TG). Most TG nerve endings are subepithelial, so this colonization implies subepithelial viral spread, where myeloid cells provide an important line of defense. The outcome of infection of myeloid cells by HSV-1 in vitro depends on their differentiation state; the outcome in vivo is unknown. Epithelial HSV-1 commonly infected myeloid cells, and Cre-Lox virus marking showed nose and lung infections passing through LysM-positive (LysM(+)) and CD11c(+) cells. In contrast, subcapsular sinus macrophages (SSMs) exposed to lymph-borne HSV-1 were permissive only when type I interferon (IFN-I) signaling was blocked; normally, their infection was suppressed. Thus, the outcome of myeloid cell infection helped to determine the HSV-1 distribution: subepithelial myeloid cells provided a route of spread from the olfactory epithelium to TG neurons, while SSMs blocked systemic spread. Herpes simplex virus 1 (HSV-1) infects most people and can cause severe disease. This reflects its persistence in nerve cells that connect to the mouth, nose, eye, and face. Established infection seems impossible to clear. Therefore, we must understand how it starts. This is difficult in humans, but mice show HSV-1 entry via the nose and then spread to its preferred nerve cells. We show that this spread proceeds in part via myeloid cells, which normally function in host defense. Myeloid infection was productive in some settings but was efficiently suppressed by interferon in others. Therefore, interferon acting on myeloid cells can stop HSV-1 spread, and enhancing this defense offers a way to improve infection control. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Inhibition of herpes simplex virus replication by tobacco extracts.

    Science.gov (United States)

    Hirsch, J M; Svennerholm, B; Vahlne, A

    1984-05-01

    Herpes simplex virus type 1 (HSV-1) has been associated with the genesis of leukoplakias, epithelial atypia, and oral cancer. Tobacco habits, such as snuff dipping, are also definitely correlated with this type of lesion. The normal cytolytic HSV-1 infection can, after in vitro inactivation, transform cells. Extracts of snuff were prepared and assayed for their ability to inhibit HSV-1 replication. Plaque formation assays of HSV-1 in the presence of snuff extract showed that a reduced number of plaques was formed. Different batches of one brand of snuff were tested for inhibition of herpes simplex virus (HSV) production. More than 99% inhibition of 24-hr HSV production was obtained with undiluted batches. The 1:5 dilutions of snuff had an inhibitory effect of 85% and 1:25 dilutions, 39%. In agreement, the attachment of the virus to the host cell and penetration of the virus to the cell nuclei were found to be inhibited as was the synthesis of viral DNA. Nicotine had an inhibitory effect, while aromatic additions to snuff were found to have no major inhibitory effect on HSV replication. Snuff extracts were prepared from different brands of snuff reported to contain high and low quantities of tobacco-specific N-nitrosamines. Brands with reported high levels of tobacco-specific N-nitrosamines had significantly greater ability to inhibit HSV replication. In conclusion, this study has shown that extracts of snuff have inhibitory effects on the production of cytolytic HSV-1 infections. A chronic snuff dipper keeps tobacco in the mouth for the major part of the day. Thus, virus shed in the oral cavity in connection with a reactivated latent HSV-1 infection has great possibilities of being affected by snuff or derivatives of snuff. It is suggested that an interaction between tobacco products and HSV-1 might be involved in the development of dysplastic lesions in the oral cavity.

  9. Necrotizing Keratitis Caused by Acyclovir-Resistant Herpes Simplex Virus

    Directory of Open Access Journals (Sweden)

    Koji Toriyama

    2014-10-01

    Full Text Available Background: We report a case of necrotizing keratitis caused by acyclovir (ACV-resistant herpes simplex virus (HSV with a clinical appearance similar to a previous fungal keratitis infection. Methods: Observational case report. Results: Penetrating keratoplasty was performed in the left eye with a history of herpetic keratitis that resolved with periodic treatment with ACV ointment and a topical steroid. The left eye was painful and red with an abscess and corneal erosion in the peripheral donor cornea. Examination of the scraped corneal epithelium by light microscopy and culturing identified Candida albicans; polymerase chain reaction (PCR was negative for human herpes viruses. After antifungal treatment, the ocular pain gradually decreased and the lesions slowly improved but recurred with a similar clinical appearance. A second light microscopy examination and cultures were negative for pathogens including C. albicans. PCR was positive for HSV-1 DNA; treatment with 3% topical ACV ointment was unsuccessful. A third examination showed only HSV-1 DNA. Despite antiviral ACV ointment, no clinical improvement occurred based on the HSV DNA copy numbers, which were the same before and after treatment, indicating a possible ACV-resistant strain. When topical trifluorothymidine was substituted for ACV, clinical improvement occurred and the HSV DNA copy numbers decreased. Conclusion: Necrotizing keratitis induced by ACV-resistant HSV occurred independently after fungal keratitis, with a similar clinical appearance in this case, making diagnosis and treatment difficult. Monitoring the HSV DNA load by real-time PCR could be useful for refractory cases even with atypical clinical appearances.

  10. Posterior Ischemic Optic Neuropathy following Herpes Zoster Ophthalmicus

    Directory of Open Access Journals (Sweden)

    Mohammad Pakravan

    2009-01-01

    Full Text Available

    PURPOSE: To report a case of posterior ischemic optic neuropathy (PION following herpes zoster ophthalmicus (HZO. CASE REPORT: A 58-year-old woman with history of recent HZO in her right eye presented with acute painless loss of vision in the same eye to no light perception. Examination revealed a positive relative afferent pupillary defect and a normal appearing optic disc. Inflammatory and infiltrative lesions of the optic nerve were ruled out by laboratory and imaging studies. The patient received systemic acyclovir and prednisolone. Three months later, visual acuity improved to counting fingers, but the optic disc became pale and atrophic leading to a presumptive diagnosis of PION. Considering the positive PCR test for varicella zoster virus and the short time interval between the two presentations, HZO was considered as the most probable cause of the optic neuropathy. CONCLUSION: Herpes zoster ophthalmicus can be associated with PION.

  11. Photodynamic treatment of Herpes simplex virus infection in vitro

    International Nuclear Information System (INIS)

    Lytle, C.D.; Hester, L.D.

    1976-01-01

    The effects of photodynamic action on in vitro herpes simplex virus infections of CV-1 monkey kidney fibroblasts or human skin fibroblasts were determined using proflavine sulfate and white fluorescent lamps. Photodynamic treatment of confluent cell monolayers prior to virus infection inactivated cell capacity, i.e. the capacity of the treated cells to support subsequent virus growth as measured by plaque formation. The capacity of human cells was more sensitive to inactivation than the capacity of monkey cells when 6 μM proflavine was used. Treated cell monolayers recovered the capacity to support virus plaque formation when virus infection was delayed four days after the treatment. Experiments in which the photodynamically treated monolayers were infected with UV-irradiated virus demonstrated that this treatment induced Weigle reactivation in both types of cells. This reactivation occurred for virus infection just after treatment or 4 days later. A Luria-Latarjet-type experiment was also performed in which cultures infected with unirradiated virus were photodynamically treated at different times after the start of infection. The results showed that for the first several hours of the virus infection the infected cultures were more sensitive to inactivation by photodynamic treatment than cell capacity. By the end of the eclipse period the infected cultures were less sensitive to inactivation than cell capacity. Results from extracellular inactivation of virus growth in monkey cells at 6 μM proflavine indicated that at physiological pH the virus has a sensitivity to photodynamic inactivation similar to that for inactivation of cell capacity. The combined data indicated that photodynamic treatment of the cell before or after virus infection could prevent virus growth. Thus, photodynamic inactivation of infected and uninfected cells may be as important as inactivation of virus particles when considering possible mechanisms in clinical photodynamic therapy for herpes

  12. Herpes simlex encephalitis. A neuropsychological and neuroradiological study

    International Nuclear Information System (INIS)

    Koga, Masaya

    1994-01-01

    Herpes simplex virus (HSV) is the most common causative pathogen of nonepidemic encephalitis in Japan. The mortality rate is approximately 30% and surviving patients often have severe sequelae such as amnestic syndrome. Between 1979 and 1992, 13 patients with herpes simplex encephalitis (HSE) were admitted to our Department. Diagnosis was based on the neurological symptoms and signs, the findings on EEG, CT and MRI, and the results of serological examination including ELISA for HSV type 1. Neuropsychological tests were performed over a period of approximatly 2 years in seven of 13 patients. The results of the tests disclosed memory impairments as follows. Namely, immediate recall was well preserved, but disturbance of recent memory and retrograde amnesia over 20 years were observed. The neuropsychological features more closely resembled those of amnestic syndrome than those of Korsakoff syndrome. The amnesia in HSE patients was characterized in the finding that it was prone to recover more gradually as compared with that following head trauma or surgical brain resection. CT scan was performed in 13 patients during the acute and convalescent stages. The low density areas were found in the temporal lobes in 60% of the patients. MRI were obtained during the convalescent stage in ten of 13 patients. In seven of the ten patients, abnormal signals were distributed uni- or bilaterally to the temporal lobe, insular and limbic system such as the hippocampus and amygdala. In the remaining three patients, the abnormal signals were localized in both hippocampi and amygdalae in one patient and only in the brain stem in another. In the last case, the MRI was normal. The findings that signal intensity on MRI showing the lesion in the temporal lobe spread continuously to the opposite limbic area or occipital lobe strongly suggested the spreading of HSV through neural fiber connections in HSE. (author)

  13. Herpes simlex encephalitis. A neuropsychological and neuroradiological study

    Energy Technology Data Exchange (ETDEWEB)

    Koga, Masaya [Kurume Univ., Fukuoka (Japan). School of Medicine

    1994-10-01

    Herpes simplex virus (HSV) is the most common causative pathogen of nonepidemic encephalitis in Japan. The mortality rate is approximately 30% and surviving patients often have severe sequelae such as amnestic syndrome. Between 1979 and 1992, 13 patients with herpes simplex encephalitis (HSE) were admitted to our Department. Diagnosis was based on the neurological symptoms and signs, the findings on EEG, CT and MRI, and the results of serological examination including ELISA for HSV type 1. Neuropsychological tests were performed over a period of approximatly 2 years in seven of 13 patients. The results of the tests disclosed memory impairments as follows. Namely, immediate recall was well preserved, but disturbance of recent memory and retrograde amnesia over 20 years were observed. The neuropsychological features more closely resembled those of amnestic syndrome than those of Korsakoff syndrome. The amnesia in HSE patients was characterized in the finding that it was prone to recover more gradually as compared with that following head trauma or surgical brain resection. CT scan was performed in 13 patients during the acute and convalescent stages. The low density areas were found in the temporal lobes in 60% of the patients. MRI were obtained during the convalescent stage in ten of 13 patients. In seven of the ten patients, abnormal signals were distributed uni- or bilaterally to the temporal lobe, insular and limbic system such as the hippocampus and amygdala. In the remaining three patients, the abnormal signals were localized in both hippocampi and amygdalae in one patient and only in the brain stem in another. In the last case, the MRI was normal. The findings that signal intensity on MRI showing the lesion in the temporal lobe spread continuously to the opposite limbic area or occipital lobe strongly suggested the spreading of HSV through neural fiber connections in HSE. (author).

  14. Hospital risk management of cutaneous herpes simplex virus infection.

    Science.gov (United States)

    Zhu, F; Zhang, J; Feng, J; Yang, H

    2016-10-01

    The epidemiology of cutaneous herpes simplex infection (CHSI) has dramatically changed over the past several decades. Valaciclovir is one of a new generation of antiviral medications that has expanded treatment options for the most common cutaneous manifestations of herpes simplex virus. However, the efficacy and safety of formulations with different doses of valaciclovir remain unclear. To carry out hospital risk management by ascertaining the incidence and risk of CHSI in patients during treatment with varying doses of valaciclovir. The PubMed, MEDLINE and Web of Science electronic databases were systematically searched from database inception to date of searching. Efficacy of drug treatment was measured by average easement score (AES). Safety was characterized as the proportion of patients with drug adverse reactions (DARs) such as fever, dizziness, headache, anxiety, irritability and yellowing of the skin. Outcomes for continuous and dichotomous data were estimated by standard mean difference (SMD) and risk ratio (RR), respectively. Five randomized controlled trials involving 1753 randomized participants for efficacy assessment and 1874 randomized participants for safety assessment were identified. Valaciclovir dose increasing from 1000 mg/day improved AES only moderately, but significantly promoted the incidence of DARs. Twice-daily treatment showed no increase in therapeutic effect but greatly increased DAR incidence. The valaciclovir dose that produced a reduction in AES was 1000 mg/day: SMD = -0.73 (95% CI -0.98 to 0.48; P < 0.01) and RR = 0.95 (95% CI 0.81-1.09; P < 0.002). Increasing the daily dose of valaciclovir does not substantially improve therapeutic efficacy for CHSI but may raise DAR incidence. Drug doses of 1000 and 2000 mg/day show no significant difference in efficacy scores, but the latter exhibits a higher incidence of DARs. The dose-dependent, long-term efficacy and safety of valaciclovir remain to be explored. © 2016 British Association of

  15. The burden of disease of Herpes Zoster in Tuscany.

    Science.gov (United States)

    Levi, Miriam; Bellini, Irene; Capecchi, Leonardo; Pieri, Luca; Bechini, Angela; Boccalini, Sara; Callaioli, Silvia; Gasparini, Roberto; Panatto, Donatella; Tiscione, Emilia; Bonanni, Paolo

    2015-01-01

    Herpes zoster (HZ) is a disease caused by the reactivation of the latent α-herpes virus varicella zoster virus (VZV), for which, in Italy, a specific surveillance system does not exist, but around 200 000 cases are estimated each year. In older patients, who are at increased risk of developing HZ, symptoms are more severe and the chances to develop postherpetic neuralgia (PHN), the most severe complication, are substantially higher. A vaccine against HZ with demonstrated efficacy and an acceptable safety profile is now available and is recommended in Europe for adults >50 years.   In anticipation of the possible introduction of an immunization programme for the elderly in Tuscany, the burden of disease caused by HZ and its complications was assessed through a retrospective analysis of the hospital discharge records between 2002 and 2012, using the ICD-9-CM 053 code. In the period 2002-2012, 4475 hospital admissions were registered with annual means of 368 hospitalizations and 39 day-hospital admissions. Most of the hospitalizations (68%) involved subjects > 65 years; the mean length of stay was 9.5 days. Slightly more than half (51.2%) of total hospital admissions were complicated cases. The most frequent were neurological complications (24.2% of total admissions), followed by ophthalmic complications (16.5%). Cases with neurological complications were those with the higher average length of stay and higher average costs for case. This study confirmed the epidemiological impact of HZ and its complications and the positive impact on morbidity that the introduction of the HZ vaccination could have in older age groups.

  16. An attenuated herpes simplex virus type 1 (HSV1 encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

    Directory of Open Access Journals (Sweden)

    Mariaconcetta Sicurella

    Full Text Available Herpes simplex virus types 1 and 2 (HSV1 and HSV2 are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat. In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ, induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1

  17. IMMUNE DISORDERS AND THEIR CORRECTION IN PATIENTS WITH HERPES INFECTION OF THE OROPHARYNX

    Directory of Open Access Journals (Sweden)

    Makarevich V.A.

    2015-12-01

    IFN-γ was elevated 1.3 times compared to control group. In our previous studies we have determined that the content of perforin-positive cytotoxic lymphocytes in patients with a high frequency of disease relapses was reduced 2 times relative to healthy donors. It was shown that HSV-inactivated vaccine was able to elevate the content of perforin-positive cytotoxic lymphocytes in patients with moderate and high recurrence rate; herewith the largest index of influence of HSV-antigen was defined in patients with a high frequency of relapses. HSV-induced production of IFN-α increased 3 times in patients with moderate frequency of relapses and it had no significant difference from the control group, and in patients with a high relapse rate - 2.3 times. Reserve ability to synthesize IFN-γ in patients with moderate frequency of HSV relapses remained at the level of index of almost healthy donors, while the expressed reduction of stimulating action of HSV antigen was observed in patients with a high relapse rate. We have previously shown that the high recurrence rate of herpes infection accompanies by reduction of levels of TNF-α, by increase of spontaneous and induced production of IL-10 (in 76% patients, IL-12 and IL-1β by monocyte cells (in 85% of cases. Herewith 67% of patients with a high frequency of disease relapses had an imbalance of IL-12p70/IL-12p40, and 43% of patients had increased production of IL-1 receptor antagonist.It was determined that incubation of PBMCs with the addition of recombinant IFN-α causes a significant increase of the production of IFN-γ in patients with moderate relapse rate and also in the control group (stimulation index 1.3. The level of interferon-induced IFN-γ had no significant difference from the basal level in patients with a high relapse rate. Regulatory effect of IFN-α manifested also as increase of production of IL-1β, herewith the increase of the ratio IL-1β/IL-1RA was noted in patients with a high relapse rate

  18. [Management of pregnant women with recurrent herpes. Guidelines for clinical practice from the French College of Gynecologists, Obstetricians (CNGOF)].

    Science.gov (United States)

    Anselem, O

    2017-12-01

    To provide guidelines for the management of woman with genital herpes during pregnancy or labor and with known history of genital herpes. MedLine and Cochrane Library databases search and review of the main foreign guidelines. Genital herpes ulceration during pregnancy in a woman with history of genital herpes correspond to a recurrence. In this situation, there is no need for virologic confirmation (Grade B). In case of recurrent herpes during pregnancy, antiviral therapy with acyclovir or valacyclovir can be administered but provide low efficiency on duration and severity of symptoms (Grade C). Antiviral treatment proposed is acyclovir (200mg 5 times daily) or valacyclovir (500mg twice daily) for 5 to 10 days (Grade C). Recurrent herpes is associated with a risk of neonatal herpes around 1% (LE3). Antiviral prophylaxis should be offered for women with recurrent genital herpes during pregnancy from 36 weeks of gestation and until delivery (Grade B). There is no evidence of the benefit of prophylaxis in case or recurrence only before the pregnancy. There is no recommendation for systematic prophylaxis for women with history of recurrent genital herpes and no recurrence during the pregnancy. At the onset of labor, virologic testing is indicated only in case of genital ulceration (Professional consensus). In case of recurrent genital herpes at the onset of labor, cesarean delivery will be all the more considered if the membranes are intact and/or in case of prematurity and/or in case of HIV positive woman and vaginal delivery will be all the more considered in case of prolonged rupture of membranes after 37 weeks of gestation in an HIV negative woman (Professional consensus). In case of recurrent genital herpes at the onset of labor and intact membranes, cesarean delivery should be considered. In case of recurrent genital herpes and prolonged rupture of membranes at term, the benefit of cesarean delivery is more questionable and vaginal delivery should be considered

  19. The Challenges and Opportunities for Development of a T-Cell Epitope-Based Herpes Simplex Vaccine

    Science.gov (United States)

    Kuo, Tiffany; Wang, Christine; Badakhshan, Tina; Chilukuri, Sravya; BenMohamed, Lbachir

    2014-01-01

    The infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a half billion individuals worldwide. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. HSV-1 infections are more prevalent than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. While genital herpes in mainly caused by HSV-2 infections, in recent years, there is an increase in the proportion of genital herpes caused by HSV-1 infections in young adults, which reach 50% in some western societies. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries their development has been notoriously difficult. During the most recent National Institute of Health (NIH) workshop titled "Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities", basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One “common denominator” among previously failed clinical herpes vaccine trials is that they either used a whole virus or whole viral proteins, which contain both pathogenic “symptomatic” and protective “asymptomatic” antigens/epitopes. In this report, we continue to advocate that using an “asymptomatic” epitope-based vaccine strategy that selectively incorporates protective epitopes which: (i) are exclusively recognized, in vitro, by effector memory CD4+ and CD8+ TEM cells from “naturally” protected seropositive asymptomatic individuals; and (ii) protect, in vivo, human leukocyte antigen (HLA) transgenic animal models from ocular and genital herpes infections and diseases, could be the answer to many of the scientific challenges facing HSV vaccine

  20. Disease burden of herpes zoster in Sweden - predominance in the elderly and in women - a register based study

    Science.gov (United States)

    2013-01-01

    Background The herpes zoster burden of disease in Sweden is not well investigated. There is no Swedish immunization program to prevent varicella zoster virus infections. A vaccine against herpes zoster and its complications is now available. The aim of this study was to estimate the herpes zoster burden of disease and to establish a pre-vaccination baseline of the minimum incidence of herpes zoster. Methods Data were collected from the Swedish National Health Data Registers including the Patient Register, the Pharmacy Register, and the Cause of Death Register. The herpes zoster burden of disease in Sweden was estimated by analyzing the overall, and age and gender differences in the antiviral prescriptions, hospitalizations and complications during 2006-2010 and mortality during 2006-2009. Results Annually, 270 per 100,000 persons received antiviral treatment for herpes zoster, and the prescription rate increased with age. It was approximately 50% higher in females than in males in the age 50+ population (rate ratio 1.39; 95% CI, 1.22 to 1.58). The overall hospitalization rate for herpes zoster was 6.9/100,000 with an approximately three-fold increase for patients over 80 years of age compared to the age 70-79 group. A gender difference in hospitalization rates was observed: 8.1/100,000 in females and 5.6/100,000 in males. Herpes zoster, with a registered complication, was found in about one third of the hospitalized patients and the most common complications involved the peripheral and central nervous systems. Death due to herpes zoster was a rare event. Conclusions The results of this study demonstrate the significant burden of herpes zoster disease in the pre-zoster vaccination era. A strong correlation with age in the herpes zoster- related incidence, hospitalization, complications, and mortality rates was found. In addition, the study provides further evidence of the female predominance in herpes zoster disease. PMID:24330510

  1. Electric hydrogen recombiner special tests

    International Nuclear Information System (INIS)

    Wilson, J.F.

    1975-12-01

    Westinghouse has produced an electric hydrogen recombiner to control hydrogen levels in reactor containments following a postulated loss-of-coolant accident. The recombiner underwent extensive testing for NRC qualification (see WCAP 7709-L and Supplements 1, 2, 3, 4). As a result, WCAP 7709-L and Supplements 1, 2, 3, and 4 have been accepted by the NRC for reference in applications not committed to IEEE-323-1974. Supplement 5 and the next supplement will demonstrate conformance to IEEE-323-1974. This supplement describes additional tests, beyond those necessary to qualify the system, which will be referenced in supplement 6. Each test has demonstrated a considerable margin of safety over required performance. Concurrently, the test results increased the fund of technical information on the electric hydrogen recombiner

  2. The effect of a single recombination event

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Jensen, Thomas Mailund; Wiuf, Carsten

    We investigate the variance in how visible a single recombination event is in a SNP data set as a function of the type of recombination event and its age. Data is simulated under the coalescent with recombination and inference is by the popular composite likelihood methods. The major determinant...... of the effect of a recombination event is the genealogical type of the event and whether SNP variation is present that can reveal the genealogical consequences of the recombination event. Recombination events that only change some branch lengths in the genealogy have a very small, but detectable, effect....... The more lineages left when the recombination event occurs, the larger effect it has, implying that it is mainly young recombination events that we detect when estimating the rate. If the population is growing, though, more lineages are present back in time and relatively more ancient recombination events...

  3. Herpes labialis and Nigerian dental health care providers: knowledge, attitudes, behaviors, and refusal to treat.

    Science.gov (United States)

    Azodo, Clement Chinedu; Umoh, Agnes O

    2015-09-15

    The few existing studies on herpes labialis among health care workers have been predominantly among non-dental health care workers. The purpose of this study was to determine Nigerian dental health care providers' knowledge of, attitudes toward, preventive behaviors for, and refusal to treat patients with herpes labialis. This cross-sectional study was conducted among final-year dental students at the University of Benin, dental house officers, and residents at the University of Benin Teaching Hospital, Benin City, Nigeria. Data collection was via a self-administered questionnaire. Bivariate statistics and logistic regression were used to relate the dependent and independent variables. Of the 120 questionnaires distributed, 110 were completed and returned, giving a 91.7% retrieval rate. However, 15 of the returned questionnaires were discarded because they were improperly completed, leaving a total of 95 questionnaires for final analysis in this study. The majority of participants were over 28 years old (54.7%), male (67.4%), unmarried (66.3%), and postgraduate dental health care providers (51.6%). Less than half (43.2%) of participants demonstrated adequate overall knowledge of herpes labialis. About one-tenth (10.5%) and more than three-quarters (87.4%) of participants reported a positive attitude and performance of adequate preventive behaviors, respectively. A total of 16.8% of participants reported a high tendency to refuse treatment to patients with herpes labialis. Although not statistically significant, young, unmarried, male undergraduate participants reported a greater likelihood to refuse treatment to herpes labialis patients. We found a statistically significant positive correlation between attitude and refusal to treat patients with herpes labialis. However, marital status and the attitude of participants toward these patients emerged as the determinants for refusal to treat patients with herpes labialis. Data from this study revealed a high level of

  4. Role of Herpes Simplex Virus 1 γ34.5 in the Regulation of IRF3 Signaling.

    Science.gov (United States)

    Manivanh, Richard; Mehrbach, Jesse; Knipe, David M; Leib, David A

    2017-12-01

    During viral infection, pattern recognition receptors (PRRs) and their associated adaptors recruit TANK-binding kinase 1 (TBK1) to activate interferon regulatory factor 3 (IRF3), resulting in production of type I interferons (IFNs). ICP0 and ICP34.5 are among the proteins encoded by herpes simplex virus 1 (HSV-1) that modulate type I IFN signaling. We constructed a recombinant virus (ΔXX) that lacks amino acids 87 to 106, a portion of the previously described TBK1-binding domain of the γ34.5 gene (D. Verpooten, Y. Ma, S. Hou, Z. Yan, and B. He, J Biol Chem 284:1097-1105, 2009, https://doi.org/10.1074/JBC.M805905200). These 20 residues are outside the γ34.5 beclin1-binding domain (BBD) that interacts with beclin1 and regulates autophagy. Unexpectedly, ΔXX showed no deficit in replication in vivo in a variety of tissues and showed virulence comparable to that of wild-type and marker-rescued viruses following intracerebral infection. ΔXX was fully capable of mediating the dephosphorylation of eIF2α, and the virus was capable of controlling the phosphorylation of IRF3. In contrast, a null mutant in γ34.5 failed to control IRF3 phosphorylation due to an inability of the mutant to sustain expression of ICP0. Our data show that while γ34.5 regulates IRF3 phosphorylation, the TBK1-binding domain itself has no impact on IRF3 phosphorylation or on replication and pathogenesis in mice. IMPORTANCE Interferons (IFNs) are potent activators of a variety of host responses that serve to control virus infections. The Herpesviridae have evolved countermeasures to IFN responses. Herpes simplex virus 1 (HSV-1) encodes the multifunctional neurovirulence protein ICP34.5. In this study, we investigated the biological relevance of the interaction between ICP34.5 and TANK-binding kinase 1 (TBK1), an activator of IFN responses. Here, we establish that although ICP34.5 binds TBK1 under certain conditions through a TBK1-binding domain (TBD), there was no direct impact of the TBD on

  5. Expression of variable viruses as herpes simplex glycoprotein D and varicella zoster gE glycoprotein using a novel plasmid based expression system in insect cell

    Directory of Open Access Journals (Sweden)

    A.M. Al-Sulaiman

    2017-11-01

    Full Text Available Several prokaryotic and eukaryotic expression systems have been used for in vitro production of viruses’ proteins. However eukaryotic expression system was always the first choice for production of proteins that undergo post-translational modification such as glycosylation. Recombinant baculoviruses have been widely used as safe vectors to express heterologous genes in the culture of insect cells, but the manipulation involved in creating, titrating, and amplifying viral stocks make it time consuming and laborious. Therefore, to facilitate rapid expression in insect cell, a plasmid based expression system was used to express herpes simplex type 1 glycoprotein D (HSV-1 gD and varicella zoster glycoprotein E (VZV gE. Recombinant plasmids were generated, transfected into insect cells (SF9, and both glycoproteins were expressed 48 h post-infection. A protein with approximately molecular weight of 64-kDa and 98-kDa for HSV-1 gD and VZV gE respectively was expressed and confirmed by SDS. Proteins were detected in insect cells cytoplasm and outer membrane by immunofluorescence. The antigenicity and immunoreactivity of each protein were confirmed by immunoblot and ELISA. Results suggest that this system can be an alternative to the traditional baculovirus expression for small scale expression system in insect cells.

  6. Isolation and characterization of two herpes simplex virus type 1 variants containing duplication of sequences within the unique long component of their genomes

    International Nuclear Information System (INIS)

    Fareed, M.U.; Maclean, A.R.; Maclean, C.A.; Fu, A.; Brown, S.M.

    1995-01-01

    This paper reports the first spontaneous isolation of two DNA duplication variants in the unique long (U L ) component of herpes simplex virus type 1 (HSV-1) strain 17 + genome, one (1719) with a duplication of 7.5 kb DNA sequences centered around Ori L and the other (1740In) with a 356 bp DNA duplication between the UL19 (MCP and UL20 open reading frames (ORFs). The variant 1719 is stable with the rare isolation of a wild type (strain 17 + ) genome presumably generated by the excision of the duplicated sequences during homologous recombination. Because of the 7.5 kb duplication, UL29 (DBP is diploid and UL30 (DNA polymerase) is present as one partial copy. Although duplication in the variant 1740In involved sequences from the UL20 ORF, the virus produces an intact UL20 gene product. Both variants show normal growth characteristics when compared with the parental viruses. DNA duplications in these variants suggest a link between replication and recombination in HSV-1. (author)

  7. Improving recombinant protein purification yield

    Science.gov (United States)

    Production of adequate amounts of recombinant proteins is essential for antibody production, biochemical activity study, and structural determination during the post-genomic era. It’s technologically challenging and a limiting factor for tung oil research because analytical reagents such as high qua...

  8. A recombinant protein expression system

    African Journals Online (AJOL)

    Aghomotsegin

    2015-06-23

    Jun 23, 2015 ... Serum free cultivation of Leishmania is cost-effective and improves large scale production of well- defined parasite material. Moreover, the production of recombinant pharmaceutical proteins requires cultivation of the host in a culture medium free of animal materials, so several culture media for.

  9. Production and recombination of gluons

    International Nuclear Information System (INIS)

    Temiraliev, A.T.

    2006-01-01

    Full text: Nonlinear Markov process of parton production has been considered. The Kolmogorov equation is applied for the evolution equation based on the approximation of independent gluons production in every decay act. We introduced a 'crossing' parameter and used the combination relations to obtain nonlinear recombination equation for the evolution of gluon structure function. (author)

  10. Recombination in hepatitis C virus.

    Science.gov (United States)

    González-Candelas, Fernando; López-Labrador, F Xavier; Bracho, María Alma

    2011-10-01

    Hepatitis C virus (HCV) is a Flavivirus with a positive-sense, single-stranded RNA genome of about 9,600 nucleotides. It is a major cause of liver disease, infecting almost 200 million people all over the world. Similarly to most RNA viruses, HCV displays very high levels of genetic diversity which have been used to differentiate six major genotypes and about 80 subtypes. Although the different genotypes and subtypes share basic biological and pathogenic features they differ in clinical outcomes, response to treatment and epidemiology. The first HCV recombinant strain, in which different genome segments derived from parentals of different genotypes, was described in St. Petersburg (Russia) in 2002. Since then, there have been only a few more than a dozen reports including descriptions of HCV recombinants at all levels: between genotypes, between subtypes of the same genotype and even between strains of the same subtype. Here, we review the literature considering the reasons underlying the difficulties for unequivocally establishing recombination in this virus along with the analytical methods necessary to do it. Finally, we analyze the potential consequences, especially in clinical practice, of HCV recombination in light of the coming new therapeutic approaches against this virus.

  11. Identification of herpes zoster associated temporal arteritis among cases of giant cell arteritis.

    Science.gov (United States)

    Buckingham, Erin M; Foley, Maria A; Grose, Charles; Syed, Nasreen A; Smith, Morton E; Margolis, Todd P; Thurtell, Matthew J; Kardon, Randy

    2017-12-30

    To examine whether herpes zoster antigen (also called varicella-zoster virus antigen) was detectable in temporal artery biopsies taken from individuals with giant cell arteritis (GCA). Retrospective comparative case series. Sections of formalin-fixed paraffin-embedded temporal arteries were examined first by hematoxylin and eosin (H&E) staining to establish the diagnosis of GCA. Adjacent sections of the same biopsy were then examined by immunohistochemistry, using 2 different monoclonal antibodies against a major antigen of varicella-zoster virus called gE. Pathological specimens were obtained from patients cared for at the University of Iowa and Washington University in St. Louis Ophthalmology Clinics. The study included biopsies from 25 patients with symptoms of GCA as well as positive H&E pathology and 25 patients with symptoms compatible with GCA but negative H&E pathology. Among the GCA-positive group, three patients had positive staining for herpes zoster antigen. Among the GCA-negative group, herpes zoster antigen was not detected in any biopsy. In both groups of patients, false positive staining for herpes zoster antigen was detected in the presence of calcifications in the arteries. False-positive staining was also detected on some extra-arterial skeletal muscle and erythrocytes. Herpes zoster antigen was detected in 3/25 temporal arteries from patients with biopsy-proven GCA. One of the three positive cases was noteworthy because the patient had had herpes zoster ophthalmicus diagnosed 3 weeks before the onset of GCA symptoms. False-positive staining for herpes zoster antigen was detected on several temporal artery biopsies. Copyright © 2017. Published by Elsevier Inc.

  12. A primary neuron culture system for the study of herpes simplex virus latency and reactivation.

    Science.gov (United States)

    Kobayashi, Mariko; Kim, Ju-Youn; Camarena, Vladimir; Roehm, Pamela C; Chao, Moses V; Wilson, Angus C; Mohr, Ian

    2012-04-02

    Herpes simplex virus type-1 (HSV-1) establishes a life-long latent infection in peripheral neurons. This latent reservoir is the source of recurrent reactivation events that ensure transmission and contribute to clinical disease. Current antivirals do not impact the latent reservoir and there are no vaccines. While the molecular details of lytic replication are well-characterized, mechanisms controlling latency in neurons remain elusive. Our present understanding of latency is derived from in vivo studies using small animal models, which have been indispensable for defining viral gene requirements and the role of immune responses. However, it is impossible to distinguish specific effects on the virus-neuron relationship from more general consequences of infection mediated by immune or non-neuronal support cells in live animals. In addition, animal experimentation is costly, time-consuming, and limited in terms of available options for manipulating host processes. To overcome these limitations, a neuron-only system is desperately needed that reproduces the in vivo characteristics of latency and reactivation but offers the benefits of tissue culture in terms of homogeneity and accessibility. Here we present an in vitro model utilizing cultured primary sympathetic neurons from rat superior cervical ganglia (SCG) (Figure 1) to study HSV-1 latency and reactivation that fits most if not all of the desired criteria. After eliminating non-neuronal cells, near-homogeneous TrkA(+) neuron cultures are infected with HSV-1 in the presence of acyclovir (ACV) to suppress lytic replication. Following ACV removal, non-productive HSV-1 infections that faithfully exhibit accepted hallmarks of latency are efficiently established. Notably, lytic mRNAs, proteins, and infectious virus become undetectable, even in the absence of selection, but latency-associated transcript (LAT) expression persists in neuronal nuclei. Viral genomes are maintained at an average copy number of 25 per neuron

  13. Most Common Dermatologic Topics Published in Five High-Impact General Medical Journals, 1970–2012: Melanoma, Psoriasis, Herpes Simplex, Herpes Zoster, and Acne

    Science.gov (United States)

    Choi, Young M; Namavar, Aram A; Wu, Jashin J

    2014-01-01

    Context: General practitioners frequently encounter skin diseases and are accustomed to diagnosing the most common dermatologic conditions. Objective: We sought to determine the most common dermatologic topics published in five high-impact general medical journals (New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, British Medical Journal (now The BMJ), and Annals of Internal Medicine). Design: We conducted an independent search of the Thomson Reuters’ Science Citation Index for common dermatologic topics, limited to the period 1970 to 2012. Main Outcome Measure: Total number of publications dealing with each dermatologic topic considered. Results: The five most common dermatologic topics published were melanoma, psoriasis, herpes simplex, herpes zoster, and acne. Melanoma and psoriasis were the top two dermatologic topics published in each journal except for Annals of Internal Medicine. Conclusions: Internists frequently diagnose herpes simplex, herpes zoster, and acne, which are also common dermatologic topics published. Although internists infrequently diagnose melanoma and psoriasis, they are major topics for general medical journals because of their increased community awareness, major advancements in therapeutic research, and their nondermatologic manifestations. PMID:25662523

  14. Most common dermatologic topics published in five high-impact general medical journals, 1970-2012: melanoma, psoriasis, herpes simplex, herpes zoster, and acne.

    Science.gov (United States)

    Choi, Young M; Namavar, Aram A; Wu, Jashin J

    2014-01-01

    General practitioners frequently encounter skin diseases and are accustomed to diagnosing the most common dermatologic conditions. We sought to determine the most common dermatologic topics published in five high-impact general medical journals (New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, British Medical Journal (now The BMJ), and Annals of Internal Medicine). We conducted an independent search of the Thomson Reuters’ Science Citation Index for common dermatologic topics, limited to the period 1970 to 2012. Total number of publications dealing with each dermatologic topic considered. The five most common dermatologic topics published were melanoma, psoriasis, herpes simplex, herpes zoster, and acne. Melanoma and psoriasis were the top two dermatologic topics published in each journal except for Annals of Internal Medicine. Internists frequently diagnose herpes simplex, herpes zoster, and acne, which are also common dermatologic topics published. Although internists infrequently diagnose melanoma and psoriasis, they are major topics for general medical journals because of their increased community awareness, major advancements in therapeutic research, and their nondermatologic manifestations.

  15. Live recombinant BHV/BRSV vaccine

    NARCIS (Netherlands)

    Keil, G.M.; Rijsewijk, F.A.M.

    1998-01-01

    The present invention refers to synthetic Bovine Respiratory Syncytium virus genes. Also the invention relates to live attenuated Bovine Herpesvirus recombinants carrying such synthetic genes. Furthermore, the invention relates to vaccines based on these live attenuated recombinants, for the

  16. Hadron production at RHIC: recombination of quarks

    Energy Technology Data Exchange (ETDEWEB)

    Fries, Rainer J [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States)

    2005-01-01

    We discuss quark recombination applied to the hadronization of a quark gluon plasma. It has been shown that the quark recombination model can explain essential features of hadron production measured in high energy heavy ion collisions.

  17. Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs

    Directory of Open Access Journals (Sweden)

    Braidwood L

    2013-12-01

    Full Text Available Lynne Braidwood,1 Sheila V Graham,2 Alex Graham,1 Joe Conner11Virttu Biologics Ltd, Department of Neurology, Southern General Hospital, Glasgow, UK; 2MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Jarrett Building, University of Glasgow, Glasgow, UKAbstract: Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVexGM-CSF], is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with “standard-of-care” drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with “standard-of-care” drugs merits further investigation, both preclinically and in the clinic. Numerous publications report

  18. Herpes zoster in breast cancer patients after radiotherapy

    International Nuclear Information System (INIS)

    Dunst, J.; Steil, B.; Furch, S.; Fach, A.; Bormann, G.; Marsch, W.

    2000-01-01

    Purpose: We have studied the incidence of herpes zoster in patients with adjuvant radiotherapy for breast cancer with special emphasis on possible correlations with other prognostic factors or survival. Patients and Methods: From 1/1985 through 12/1993, 1 155 breast cancer patients received postoperative radiotherapy with curative intent in our department. After mastectomy 961 patients were irradiated and after breast-preserving treatment 194 patients. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3 to 12.4 years). There were 443 women (38%) pre- and 712 (62%) postmenopausal. 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. In case of postmastectomy radiotherapy, the lateral chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field to 50 Gy (axilla 44 Gy) and most of the chest wall with an electron field to 44 Gy in 2-Gy fractions. After breast-preservation, the breast was irradiated via tangential fields with 6- to 8-MV photons up to 50 Gy plus 8 Gy electron boost to the tumor bed. Most of the patients were followed routinely in the department for 2 to 5 years. The frequency of zoster was determined retrospectively by reviewing the patients' records. Results: A zoster after radiotherapy occurred in 41/1 155 patients (3.7%), mostly within the first 2 years after completion of radiotherapy. All infections remained localized and there was no evidence for systemic infections. Type of treatment (mastectomy vs breast-preservation) had no impact on the frequency of herpes zoster (36/961 patients after mastectomy and 5/194 patients after breast-preservation). There was also no correlation with other prognostic factors such as age, menopausal status, stage of disease or the use of adjuvant chemotherapy, nor was the occurrence of zoster linked to the degree of acute skin reaction in the

  19. High efficiency recombineering in lactic acid bacteria

    OpenAIRE

    van Pijkeren, Jan-Peter; Britton, Robert A.

    2012-01-01

    The ability to efficiently generate targeted point mutations in the chromosome without the need for antibiotics, or other means of selection, is a powerful strategy for genome engineering. Although oligonucleotide-mediated recombineering (ssDNA recombineering) has been utilized in Escherichia coli for over a decade, the successful adaptation of ssDNA recombineering to Gram-positive bacteria has not been reported. Here we describe the development and application of ssDNA recombineering in lact...

  20. Population inversion in recombining hydrogen plasma

    International Nuclear Information System (INIS)

    Furukane, Utaro; Yokota, Toshiaki; Oda, Toshiatsu.

    1978-11-01

    The collisional-radiative model is applied to a recombining hydrogen plasma in order to investigate the plasma condition in which the population inversion between the energy levels of hydrogen can be generated. The population inversion is expected in a plasma where the three body recombination has a large contribution to the recombining processes and the effective recombination rate is beyond a certain value for a given electron density and temperature. Calculated results are presented in figures and tables. (author)

  1. Herpes simplex virus type 1 and type 2 in the Netherlands : seroprevalence, risk factors and changes during a 12-year period

    NARCIS (Netherlands)

    Woestenberg, Petra J; Tjhie, Jeroen H T; de Melker, Hester E; van der Klis, Fiona R M; van Bergen, Jan E A M; van der Sande, Marianne A B; van Benthem, Birgit H B

    2016-01-01

    BACKGROUND: Genital herpes results in considerable morbidity, including risk of neonatal herpes, and is increasingly being caused by Herpes Simplex Virus (HSV) type 1. Possibly children are less often HSV-1 infected, leaving them susceptible until sexual debut. We assessed changes in the Dutch HSV-1

  2. Herpes simplex virus type 1 and type 2 in the Netherlands: seroprevalence, risk factors and changes during a 12-year period

    NARCIS (Netherlands)

    Woestenberg, Petra J.; Tjhie, Jeroen H. T.; de Melker, Hester E.; van der Klis, Fiona R. M.; van Bergen, Jan E. A. M.; van der Sande, Marianne A. B.; van Benthem, Birgit H. B.

    2016-01-01

    Genital herpes results in considerable morbidity, including risk of neonatal herpes, and is increasingly being caused by Herpes Simplex Virus (HSV) type 1. Possibly children are less often HSV-1 infected, leaving them susceptible until sexual debut. We assessed changes in the Dutch HSV-1 and HSV-2

  3. No evidence of parvovirus B19, Chlamydia pneumoniae or human herpes virus infection in temporal artery biopsies in patients with giant cell arteritis

    DEFF Research Database (Denmark)

    Helweg-Larsen, J; Tarp, B; Obel, N

    2002-01-01

    conditions. DNA was extracted from frozen biopsies and PCR was used to amplify genes from Chlamydia pneumoniae, parvovirus B19 and each of the eight human herpes viruses: herpes simplex viruses HSV-1 and 2, Epstein-Barr virus, cytomegalovirus, varicella zoster virus and human herpes viruses HHV-6, -7 and -8...

  4. Molecular and serologic diagnostic approaches; the prevalence of herpes simplex in idiopathic men infertile

    Science.gov (United States)

    Amirjannati, Nasser; Yaghmaei, Farhad; Akhondi, Mohammad Mehdi; Nasiri, Mahboubeh; Heidari-Vala, Hamed; Sehhat, Zahra

    2014-01-01

    Background: Human pathogens that can cause infertility may also affect sperm count and quality. Viral infections can be considered as direct and/or indirect cause of male factor infertility. Objective: Our goal was to investigate the prevalence of herpes simplex virus in the semen of infertile men attending the Avicenna Infertility Clinic, and to compare it with the herpes virus serology results. Materials and Methods: This cross sectional study was conducted during 2009-2010. Infertile men participating without any clinical signs of infection with herpes simplex virus, and no obvious cause for their infertility were included. Semen and blood samples were used for Polymerase Chain Reaction (PCR) and serologic testing for these people. Two samples were collected: one ml semen sample to verify the existence of genital herpes simplex virus in infertile men, and blood samples of 217 individuals tested for antibodies to herpes simplex virus. Data were analyzed by SPSS 16. Results: According to the PCR results of semen samples the prevalence of herpes simplex in semen was 12% and serologic test showed 3.2% prevalence within blood. Nine to 10% of IgM negative were PCR positive and only 2-3% of IgM positive were PCR positive. Between herpes serologic studies with positive controls and negative controls by using both tests, there was a significant positive relationship (r=0.718 and p<0.001). The relationship between semen PCR test results and serological survey of herpes patients with a negative control in both Pearson and Spearman tests was positive and significant (r=0.229 and p=0.001). Correlation between the PCR results of semen samples with two positive control subjects and a positive IgM test was statistically confirmed (r=0.235 and p<0.001). Conclusion: We recommend that if there is suspicion to herpes simplex as a microorganism that theoretically could impact semen parameters and cause infertility it is prudent to use PCR technique on semen sample rather than ELISA

  5. Cloning, purification and characterization of recombinant silkworm ...

    African Journals Online (AJOL)

    The recombinant His-tagged BmAK protein was expressed in soluble form in Escherichia coli Rosetta and purified by metal chelating affinity chromatography. The amino acid sequence of recombinant protein was confirmed by mass spectroscopic analysis and the enzyme activity assay that indicated the recombinant ...

  6. Determination of recombination in Mycoplasma hominis

    DEFF Research Database (Denmark)

    Jacobsen, Iben Søgaard; Boesen, Thomas; Mygind, Tina

    2002-01-01

    indicating the presence of recombination. In order to test for intergenic recombination, phylogenetic trees were reconstructed for each of the genes but no well-supported bifurcating phylogenetic trees could be obtained. The genes were tested for intragenic recombination using the correlation between linkage...

  7. Comparing the effect of diode laser against acyclovir cream for the treatment of herpes labialis.

    Science.gov (United States)

    Honarmand, Marieh; Farhadmollashahi, Leila; Vosoughirahbar, Ehsan

    2017-06-01

    Recently alternative therapies such as the use of diode laser therapy have been introduced for recurrent herpes labial infection. The aim of this study was to evaluate the effectiveness of diode laser for treatment of recurrent herpes labialis. This was single-blind randomized clinical trial to evaluate the efficacy of diode laser for the treatment of recurrent herpes labial. In total, 60 patients whit recurrent herpes simplex labialis were selected and randomly divided in to three groups. 20 patients received treatment whit diode laser (at a wavelength of 870 nm, energy density 4.5 j/cm2), 20 patients were treated with acyclovir cream 5%, 20 patients received treatment with laser-off (placebo). The end point was lesions crusting. Data analyzed by Tukey HSD Test and One-way ANOVA (at a significance level of 0.05) in SPSS-20 software. The mean length of recovery time (day) in the laser, off laser, and acyclovir groups was 2.20±0.41, 4.30±1.03, and 3.4±1.142, respectively. There is a significant difference between three groups in this regard ( P diode laser reduced the length of recovery time and pain severity faster than treatment with acyclovir cream. Key words: Recurrent herpes labial, Acyclovir, Low level laser therapy.

  8. [Possibilities for the treatment of varicella-herpes zoster infections in juvenile leukemia].

    Science.gov (United States)

    Exadaktylos, P; Grävinghoff, J

    1976-01-01

    Chicken pox and herpes zoster represent afraid complications in patients with malignant diseases which may take a noxious course. During the sequence of two chicken pox epidemias in 1973 in children with acute lymphoblastic leukaemias, the prevention and therapeutic possibilities were checked again. Chicken pox or herpes zoster convalescent sera being compatible for blood groups and zoster-immunoglobulin were not available. At the time of the epidemia the first reports on the effect of cytarabine (Alexan) were published. Moreover, we received an information on the therapeutic application of small pox vaccine inactivated with formaldehyde (vaccinia antigen) in adults with herpes zoster and herpes labialis. From 10 children with leukaemias, who were affected with chicken pox or herpes zoster, 7 received up to 1.0 ml of inactivated small pox vaccine intramuscularly on the first day of manifestation. In 6 of the patients there were no new efflorescences on the third day. A third child died. First of all it seems probable that this influence may be due to an induction of interferon formation. Further studies will have to elucidate to what extent this mechanism will also be efficient in severe cases of immunosuppression.

  9. Two cases of herpes simplex esophagitis during treatment for lung cancer

    International Nuclear Information System (INIS)

    Tajiri, Tomoko; Ikeue, Tatsuyoshi; Sugita, Takakazu; Morita, Kyohei; Maniwa, Ko; Watanabe, Shigeki; Hirokawa, Sadao; Nishiyama, Hideki; Maekawa, Nobuo

    2007-01-01

    Herpes simplex virus (HSV) is one of the three major causes of infectious esophagitis, along with Candida albicans and Cytomegalo virus (CMV). Most cases occur in immunocompromised hosts, in whom this can be life threatening. We report two cases of herpes simplex esophagitis occurring during treatment for lung cancer. An 80-year-old man with radiation pneumonia caused by radiotherapy for lung cancer was admitted for treatment with antibiotics and corticosteroids. Shortly after initiation of treatment, he complained of dysphasia. Endoscopic examination revealed herpes simplex esophagitis. A 71-year-old man was given corticosteroids for cryptogenic organizing pneumonia following chemotherapy for lung cancer. During treatment, the patient complained of odynophagia. Endoscopic examination revealed herpes simplex esophagitis. Both cases died due to progression of lung cancer and acute respiratory distress syndrome, despite administration of acyclovir. When immunocompromised patients complain of prolonged dysphagia and odynophagia, the presence of herpes simplex esophagitis should be clarified by endoscopic examination. It is occasionally difficult to distinguish between HSV and Candida esophagitis by endoscopic observation alone. Esophageal mucosal endoscopic cytology can help differentiate between these three infectious agents. (author)

  10. The Shozu Herpes Zoster (SHEZ) Study: Rationale, Design, and Description of a Prospective Cohort Study

    Science.gov (United States)

    Takao, Yukiko; Miyazaki, Yoshiyuki; Onishi, Fumitake; Kumihashi, Hideaki; Gomi, Yasuyuki; Ishikawa, Toyokazu; Okuno, Yoshinobu; Mori, Yasuko; Asada, Hideo; Yamanishi, Koichi; Iso, Hiroyasu

    2012-01-01

    Background The incidence and risk factors for herpes zoster have been studied in cross-sectional and cohort studies, although most such studies have been conducted in Western countries. Evidence from Asian populations is limited, and no cohort study has been conducted in Asia. We are conducting a 3-year prospective cohort study in Shozu County in Kagawa Prefecture, Japan to determine the incidence and predictive and immunologic factors for herpes zoster among Japanese. Methods The participants are followed for 3 years, and a telephone survey is conducted every 4 weeks. The participants were assigned to 1 of 3 studies. Participants in study A gave information on past history of herpes zoster and completed health questionnaires. Study B participants additionally underwent varicella-zoster virus (VZV) skin testing, and study C participants additionally underwent blood testing. If the participants develop herpes zoster, we evaluate clinical symptoms, measure cell-mediated immunity and humoral immunity using venous blood sampling, photograph skin areas with rash, conduct virus identification testing by polymerase chain reaction (PCR) and virus isolation from crust sampling, and evaluate postherpetic pain. Results We recruited 12 522 participants aged 50 years or older in Shozu County from December 2009 through November 2010. The participation rate was 65.7% of the target population. Conclusions The present study is likely to provide valuable data on the incidence and predictive and immunologic factors for herpes zoster in a defined community-based population of Japanese. PMID:22343323

  11. Protein sequences clustering of herpes virus by using Tribe Markov clustering (Tribe-MCL)

    Science.gov (United States)

    Bustamam, A.; Siswantining, T.; Febriyani, N. L.; Novitasari, I. D.; Cahyaningrum, R. D.

    2017-07-01

    The herpes virus can be found anywhere and one of the important characteristics is its ability to cause acute and chronic infection at certain times so as a result of the infection allows severe complications occurred. The herpes virus is composed of DNA containing protein and wrapped by glycoproteins. In this work, the Herpes viruses family is classified and analyzed by clustering their protein-sequence using Tribe Markov Clustering (Tribe-MCL) algorithm. Tribe-MCL is an efficient clustering method based on the theory of Markov chains, to classify protein families from protein sequences using pre-computed sequence similarity information. We implement the Tribe-MCL algorithm using an open source program of R. We select 24 protein sequences of Herpes virus obtained from NCBI database. The dataset consists of three types of glycoprotein B, F, and H. Each type has eight herpes virus that infected humans. Based on our simulation using different inflation factor r=1.5, 2, 3 we find a various number of the clusters results. The greater the inflation factor the greater the number of their clusters. Each protein will grouped together in the same type of protein.

  12. Dendritic cells in the cornea during Herpes simplex viral infection and inflammation.

    Science.gov (United States)

    Kwon, Min S; Carnt, Nicole A; Truong, Naomi R; Pattamatta, Ushasree; White, Andrew J; Samarawickrama, Chameen; Cunningham, Anthony L

    2017-11-10

    Herpes simplex keratitis is commonly caused by Herpes simplex virus type 1, which primarily infects eyelids, corneas, or conjunctiva. Herpes simplex virus type 1-through sophisticated interactions with dendritic cells (DCs), a type of antigen-presenting cell)-initiates proinflammatory responses in the cornea. Corneas were once thought to be an immune-privileged region; however, with the recent discovery of DCs that reside in the cornea, this long-held conjecture has been overturned. Therefore, evaluating the clinical, preclinical, and cell-based studies that investigate the roles of DCs in corneas infected with Herpes simplex virus is critical. With in vivo confocal microscopy, animal models, and cell culture experiments, we may further the understanding of the sophisticated interactions of Herpes simplex virus with DCs in the cornea and the molecular mechanism associated with it. It has been shown that specific differentiation of DCs using immunohistochemistry, flow cytometry, and polymerase chain reaction analysis in both human and mice tissues and viral tissue infections are integral to increasing understanding. As for in vivo confocal microscopy, it holds promise as it is the least invasive and a real-time investigation. These tools will facilitate the discovery of various targets to develop new treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Functional decline and herpes zoster in older people: an interplay of multiple factors.

    Science.gov (United States)

    2015-12-01

    Herpes zoster is a frequent painful infectious disease whose incidence and severity increase with age. In older people, there is a strong bidirectional link between herpes zoster and functional decline, which refers to a decrement in ability to perform activities of daily living due to ageing and disabilities. However, the exact nature of such link remains poorly established. Based on the opinion from a multidisciplinary group of experts, we here propose a new model to account for the interplay between infection, somatic/psychiatric comorbidity, coping skills, polypharmacy, and age, which may account for the functional decline related to herpes zoster in older patients. This model integrates the risk of decompensation of underlying disease; the risk of pain becoming chronic (e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications; the detrimental impact of herpes zoster on quality of life, functioning, and mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and ageing; and the role of stressful life events in the infection itself and comorbid depression. This model underlines the importance of early treatment, strengthening coping, and vaccine prevention.

  14. Application and tolerability of Herpotherm(®) in the treatment of genital herpes.

    Science.gov (United States)

    Schlippe, Gerrit; Voss, Werner; Brenn, Lars Christian

    2013-01-01

    Genital herpes is the manifestation of a herpes simplex virus 2 infection. Standard treatment uses both local and systemic approaches. Here, we report on the results of a local therapy approach with 31 female patients at a gynecological practice. In the here-described approach, established genital herpes infection was treated with the medical device Herpotherm(®), with or without virostatic drugs. Herpotherm(®) is a certified medical device operating on the basis of local heat application. Parameters evaluated during the approach were (i) subjective patient assessments and (ii) objective assessment of the physician. In the described therapy approach a positive effect in terms of nature and severity in the course of the disease using Herpotherm(®) could be demonstrated. It could be shown that Herpotherm(®) can also be used for genital herpes and that it is well tolerated. In relation to other therapies using topical treatment for genital herpes, an extremely rapid reduction of pain and herpetic symptoms could be observed. Intolerances or discontinued use as a result of complications were not observed.

  15. A suspected dental cellulitis leading to diagnosis of both herpes zoster ophthalmicus and HIV

    Directory of Open Access Journals (Sweden)

    Grace E. Parkins, BDS, FDS.RCPS (Glas., FWACS, FGCS

    2015-03-01

    Full Text Available Herpes zoster ophthalmicus and HIV are serious health problems. We report a case of a 37-year-old woman who presented to the Korle-Bu Teaching Hospital with dyspnea and facial cellulitis, and a diagnosis 5 days prior of dental cellulitis made at a district hospital. Investigations revealed that the facial cellulitis was secondary to herpes zoster infection involving the ophthalmic division of the left trigeminal nerve. The patient responded well to oral acyclovir but developed postherpetic neuralgia. During the course of treatment, she was also diagnosed to be HIV-1 positive and was referred for further management. This case represents a unique report in which the patient presented to the hospital with symptoms of cellulitis suggestive of underlying dental infection but was later diagnosed with both herpes zoster ophthalmicus and an underlying HIV infection. Atypical presentations of herpes zoster can occur in HIV/AIDS. Signs of herpes zoster infection with cellulitis should alert the clinician that the patient may have a possible underlying immunosuppressive disease. The population must be educated regarding the importance of early presentation and careful compliance with treatment as well as regular follow-ups.

  16. To Test or Not to Test? Campus Health Officials Grapple with Questions about Screening Students for Genital Herpes

    Science.gov (United States)

    Farrell, Elizabeth F.

    2005-01-01

    According to the Centers for Disease Control, 17 percent of 20- to 29-year-olds are infected with genital herpes, one of the most common sexually-transmitted diseases in the United States. Because of lack or mildness of symptoms and the tendency to not test for herpes during routine medical exams, the disease can go undiagnosed and can easily be…

  17. A comparative analysis of polymerase chain reaction and direct fluorescent antibody test for diagnosis of genital herpes

    Directory of Open Access Journals (Sweden)

    Vrushali Patwardhan

    2017-01-01

    Conclusion: PCR was found to be better in the detection of HSV in recurrent genital herpes patients. It is a better modality, especially when genital herpes clinically presents with ulcerative or crusted lesions, and is also a cheaper alternative as compared to DFA.

  18. Whole Blood Polymerase Chain Reaction in a Neonate with Disseminated Herpes Simplex Virus Infection and Liver Failure

    Directory of Open Access Journals (Sweden)

    Jennifer A. Scoble

    2013-10-01

    Full Text Available A late preterm neonate born by cesarean section with intact membranes presented at 9 days of life with shock and liver failure. Surface cultures were negative but whole blood polymerase chain reaction was positive for herpes simplex virus type 2, underscoring the value of this test in early diagnosis of perinatally acquired disseminated herpes simplex virus infection without skin lesions.

  19. The association between herpes virus infections and functional somatic symptoms in a general population of adolescents. The TRAILS study

    NARCIS (Netherlands)

    Jonker, Iris; Schoevers, Robert; Klein, Hans; Rosmalen, Judith

    2017-01-01

    Background FSS have been suggested to follow activation of the immune system, triggered by herpes virus infections. The aim of this study was to find out whether herpes virus infections were associated with the experience of FSS in adolescents, and whether this association was mediated by hsCRP, as

  20. The human herpes virus 8-encoded chemokine receptor is required for angioproliferation in a murine model of Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Jensen, Kristian K; Manfra, Denise J; Grisotto, Marcos G

    2005-01-01

    Kaposi's sarcoma (KS)-associated herpesvirus or human herpes virus 8 is considered the etiological agent of KS, a highly vascularized neoplasm that is the most common tumor affecting HIV/AIDS patients. The KS-associated herpesvirus/human herpes virus 8 open reading frame 74 encodes a constitutively...

  1. A Strategy for Cultivation of Retargeted Oncolytic Herpes Simplex Viruses in Non-cancer Cells.

    Science.gov (United States)

    Leoni, Valerio; Gatta, Valentina; Casiraghi, Costanza; Nicosia, Alfredo; Petrovic, Biljana; Campadelli-Fiume, Gabriella

    2017-05-15

    The oncolytic herpes simplex virus (HSV) that has been approved for clinical practice and those HSVs in clinical trials are attenuated viruses, often with the neurovirulence gene γ 1 34.5 and additional genes deleted. One strategy to engineer nonattenuated oncolytic HSVs consists of retargeting the viral tropism to a cancer-specific receptor of choice, exemplified by HER2 (human epidermal growth factor receptor 2), which is present in breast, ovary, and other cancers, and in detargeting from the natural receptors. Because the HER2-retargeted HSVs strictly depend on this receptor for infection, the viruses employed in preclinical studies were cultivated in HER2-positive cancer cells. The production of clinical-grade viruses destined for humans should avoid the use of cancer cells. Here, we engineered the R-213 recombinant, by insertion of a 20-amino-acid (aa) short peptide (named GCN4) in the gH of R-LM113; this recombinant was retargeted to HER2 through insertion in gD of a single-chain antibody (scFv) to HER2. Next, we generated a Vero cell line expressing an artificial receptor (GCN4R) whose N terminus consists of an scFv to GCN4 and therefore is capable of interacting with GCN4 present in gH of R-213. R-213 replicated as well as R-LM113 in SK-OV-3 cells, implying that addition of the GCN4 peptide was not detrimental to gH. R-213 grew to relatively high titers in Vero-GCN4R cells, efficiently spread from cell to cell, and killed both Vero-GCN4R and SK-OV-3 cells, as expected for an oncolytic virus. Altogether, Vero-GCN4R cells represent an efficient system for cultivation of retargeted oncolytic HSVs in non-cancer cells. IMPORTANCE There is growing interest in viruses as oncolytic agents, which can be administered in combination with immunotherapeutic compounds, including immune checkpoint inhibitors. The oncolytic HSV approved for clinical practice and those in clinical trials are attenuated viruses. An alternative to attenuation is a cancer specificity

  2. Epidemiologic aspects of recurrent herpes labialis among Jordanian University students.

    Science.gov (United States)

    Sawair, Faleh A; Jassim, Zahra A; Malkawi, Ziad A; Jamani, Kifah D

    2010-07-01

    To study the epidemiologic aspects of recurrent herpes labialis (RHL) in a young adult population and to evaluate treatments used by affected patients. A cross-sectional survey conducted on a random sample of 1000 students of The University of Jordan, Amman, Jordan between May and September 2008. Subjects with RHL were identified and asked to describe their disease and its management. Chi-square and t-test were used to compare differences between groups. The point prevalence of RHL was 2.3%, annual prevalence was 17%, and lifetime prevalence was 26.4%. The prevalence was related to the place of living, income, and college, but not to gender, marital status, medical history, smoking, or aphthous stomatitis. Eruptions occurred mostly on the left side of the lower lip and systemic upset, stress, and cold weather were the main triggering events. The mean age of onset was approximately 15 years. Of the cases, 51.2% reported at least 2 recurrences annually and 61.7% had positive family history. Nearly one-half of cases have treated the lesions and only 18.2% have used antiviral therapies. Some used lipstick, vaseline, tahini, or toothpaste to cover lesions. Treatment was recommended mostly by relatives and friends, only 26.3% sought treatment advice from medical practitioners. A high prevalence of RHL among this population was found. There is a need to educate patients with RHL on treatment options available to reduce their distress and to improve their quality of life.

  3. Herpes Simplex Virus Type 1 Infection Associated with Atrial Myxoma

    Science.gov (United States)

    Li, Yanwen; Pan, Zhigang; Ji, Yuan; Sheppard, Mary; Jeffries, Donald J.; Archard, Leonard C.; Zhang, Hongyi

    2003-01-01

    Some findings suggest an infectious factor in cardiac myxoma and certain histopathological features indicate herpes simplex virus type 1 (HSV-1) infection. We hypothesized that HSV-1 may be involved in the pathogenesis of cardiac myxoma. Paraffin-embedded tissue samples from 17 patients with atrial myxoma were investigated for HSV-1 antigen by immunohistochemistry and viral genomic DNA by nested polymerase chain reaction. The histogenesis and oncogenesis of atrial myxoma were assessed by the expression of calretinin, Ki67, and p53 protein, respectively. Autopsy myocardial samples, including endocardium from 12 patients who died by accident or other conditions, were used for comparison. HSV-1 antigen was detected in atrial myxoma from 12 of 17 patients: 8 of these 12 samples were positive also for HSV-1 DNA. No HSV-1 antigen or DNA was found in tissue from the comparison group. Antigens of HSV-2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were not found in atrial myxoma. Calretinin was found in myxoma cells of all 17 cases but Ki67 was present only in smooth muscle cells or infiltrating cells in some cases. p53 was not detectable in any myxoma. Most infiltrating cells were cytotoxic T lymphocytes. These data suggest that HSV-1 infection is associated with some cases of sporadic atrial myxoma and that these may result from a chronic inflammatory lesion of endocardium. PMID:14633612

  4. Detection of Herpes Simplex Virus DNA in Pseudoexfoliation Syndrome

    Directory of Open Access Journals (Sweden)

    Masoomeh Eghtedari

    2009-06-01

    Full Text Available Background: Pseudoexfoliation syndrome is one of the mostcommon identifiable causes of open angle glaucoma. It hasunknown etiology and pathogenesis. Infection, possibly viral,is one of the proposed pathogenic mechanisms in this condition.In the present study the presence of herpes simplex virus(HSV in specimens of anterior lens capsule of patients withpseudoexfoliation syndrome has been assessed.Methods: The presence of HSV- DNA was searched by usingpolymerase chain reaction method in specimens of anteriorlens capsule (5 mm diameter of 50 patients with pseudoexfoliationsyndrome (study group and 50 age-matchedpatients without the disease (control group who underwentcataract or combined cataract and glaucoma surgery duringa one-year (2006-2007 period in Khalili Hospital, Shiraz,Iran. The results were compared statistically with Chisquaretest and independent samples t test using SPSS software(version 11.5.Results: HSV type I DNA was detected in 18% of the patientsin the study group compared with 2% in the control group (Chisquare test, P = 0.008. The difference between the ranges ofintraocular pressure in the two groups was not statistically significant.Conclusion: The presence of HSV type I DNA suggests thepossible relationship between the virus and pseudoexfoliationsyndrome. It may be a treatable etiology in this multi-factorialdisorder and may help to future management of patients; especiallyto prevent some of the complications in this syndrome.

  5. Rubella, herpes simplex virus type 2 and preeclampsia.

    Science.gov (United States)

    Alshareef, Shimos A; Eltom, Ahmed M; Nasr, Abubakr M; Hamdan, Hamdan Z; Adam, Ishag

    2017-07-26

    Preeclampsia is a major health problem. Although, the pathophysiology of preeclampsia is not fully understood, there are recent studies on association between infections and preeclampsia. The aim of the present study was to investigate the association between maternal seropositivity of rubella, Herpes simplex virus type 2 (HSV-2) and preeclampsia. A case -controls study (90 women in each arm) was conducted at Saad Abualila Maternity Hospital, Khartoum, Sudan. The cases were women with preeclampsia and the controls were healthy pregnant women. Rubella and HSV-2 IgG antibodies were analysed in the maternal sera of all of the participants using ELISA. There was no significant difference in the age, parity and gestational age between the two groups. Maternal serum IgG seropositivity for rubella (92.2% vs. 34.4%, P rubella (3.3% vs. 2.2%, P = 0.650) and HSV-2 (2.2% vs. 1.1%, P = 0.560). All the IgM seropositive cases were IgG seropositive too. In binary logistic regression women with rubella (OR = 4.93; 95% CI = 2.082-11.692, P rubella and HSV-2 IgG seropositivity is associated with preeclampsia. Preventive measure should be implemented.

  6. Human herpes virus 6 infection in pediatric organ transplant patients.

    Science.gov (United States)

    Ylinen, Elisa; Lehtinen, Silja; Jahnukainen, Timo; Karlsson, Teemu; Loginov, Raisa; Mannonen, Laura; Lautenschlager, Irmeli; Jalanko, Hannu

    2017-06-01

    Transplant patients need lifelong immunosuppressive medication, but this reduces their defense mechanisms, making them prone to viral infections and reactivations. We aimed to clarify the prevalence and clinical manifestations of the human herpes virus 6 (HHV-6) infection in children after pediatric solid organ transplants. Clinical findings and viral loads were compared between primary HHV-6 infections and reactivations. The study comprised 47 kidney, 25 liver, and 12 heart transplant patients who underwent surgery from 2009 to 2014. HHV-6 antibodies were analyzed before surgery, and HHV-6 DNAemia tests were regularly carried out after the transplant using a real-time quantitative polymerase chain reaction method. We found the primary HHV-6 infection in 19 of 22 (86%) seronegative patients, and it was more common in patients under 3 years of age (79%) than over 3 (38%, P=.0002). Post-transplant HHV-6 DNAemia affected 48 of 84 (57%) patients and was significantly higher in primary infections than reactivations (P=.001), and 17 of 48 (35%) patients had symptoms when it was detected at a median of 2 weeks post-transplant. The HHV-6 infection was common after solid organ transplants, especially under 3 years of age, and it typically started 2 weeks after surgery. Testing for HHV-6 DNAemia is recommended shortly after transplantation, especially in patients with fever, diarrhea, rash, seizures, or abnormal liver enzyme tests. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Higher Throughput Quantification of Neutralizing Antibody to Herpes Simplex Viruses.

    Directory of Open Access Journals (Sweden)

    Tamara P Blevins

    Full Text Available We report a rapid, higher throughput method for measuring neutralizing antibody to herpes simplex virus (HSV in human sera. Clinical isolates and sera from the Herpevac Trial for Women were used in a colorimetric assay in which infection of tissue culture (lack of neutralization was indicated by substrate metabolism by beta-galactosidase induced in the ELVIS cell line. The neutralization assay was optimized by addition of guinea pig complement, which particularly enhanced neutralizing antibody titers to HSV-2. Higher neutralizing antibody titers were also achieved using virus particles isolated from the supernatant of infected cells rather than lysate of infected cells as the source of virus. The effect of assay incubation time and incubation time with substrate were also optimized. We found that incubating with substrate until a standard optical density of 1.0 was reached permitted a better comparison among virus isolates, and achieved reliable measurement of neutralizing antibody activity. Interestingly, in contrast to results in the absence of complement, addition of complement allowed sera from HSV-2 gD-vaccinated subjects to neutralize HSV-1 and HSV-2 clinical and laboratory isolates with equal potency.

  8. Radioimmunoassay for herpes simplex virus (HSV) thymidine kinase

    International Nuclear Information System (INIS)

    McGuirt, P.V.; Keller, P.M.; Elion, G.B.

    1982-01-01

    A sensitive RIA for HSV-1 thymidine kinase (TK) has been developed. This assay is based on competition for the binding site of a rabbit antibody against purified HSV-1 TK, between a purified 3 H-labeled HSV-1 TK and a sample containing an unknown amount of viral TK. The assay is capable of detecting 8 ng or more of the HSV enzyme. Purified HSV-1 TK denatured to <1% of its original kinase activity is as effective in binding to the antibody as is native HSV-1 TK. Viral TK is detectable at ranges of 150-460 ng/mg protein of cell extract from infected cells or cells transformed by HSV or HSV genetic material. HSV-2 TK appears highly cross-reactive, VZV TK is slightly less so, and the vaccinia TK shows little or no cross-reactivity. This RIA may serve as a tool for monitoring the expression of the HSV TK during an active herpes virus infection, a latent ganglionic infection, or in neoplastic cells which may have arisen by viral transformation

  9. Vaccine profile of herpes zoster (HZ/su) subunit vaccine.

    Science.gov (United States)

    Cunningham, Anthony L; Heineman, Thomas

    2017-07-01

    Herpes zoster (HZ) causes an often severe and painful rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN) and by dissemination in immune-compromised patients. HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age-related or other causes of decreased T cell immunity. A live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 8 years. Areas covered: A new HZ subunit (HZ/su) vaccine combines a key surface VZV glycoprotein (E) with a T cell-boosting adjuvant system (AS01 B ) and is administered by two intramuscular injections two months apart. Expert commentary: HZ/su showed excellent efficacy of ~90% in immunocompetent adults ≥50 and ≥70 years of age, respectively, in the ZOE-50 and ZOE-70 phase III controlled trials. Efficacy was unaffected by advancing age and persisted for >3 years. Approximately 9.5% of subjects had severe, but transient (1-2 days) injection site pain, swelling or redness. Compliance with both vaccine doses was high (95%). The vaccine will have a major impact on HZ management. Phase I-II trials showed safety and immunogenicity in severely immunocompromised patients. Phase III trial results are expected soon.

  10. Stabilising the Herpes Simplex Virus capsid by DNA packaging

    Science.gov (United States)

    Wuite, Gijs; Radtke, Kerstin; Sodeik, Beate; Roos, Wouter

    2009-03-01

    Three different types of Herpes Simplex Virus type 1 (HSV-1) nuclear capsids can be distinguished, A, B and C capsids. These capsids types are, respectively, empty, contain scaffold proteins, or hold DNA. We investigate the physical properties of these three capsids by combining biochemical and nanoindentation techniques. Atomic Force Microscopy (AFM) experiments show that A and C capsids are mechanically indistinguishable whereas B capsids already break at much lower forces. By extracting the pentamers with 2.0 M GuHCl or 6.0 M Urea we demonstrate an increased flexibility of all three capsid types. Remarkably, the breaking force of the B capsids without pentamers does not change, while the modified A and C capsids show a large drop in their breaking force to approximately the value of the B capsids. This result indicates that upon DNA packaging a structural change at or near the pentamers occurs which mechanically reinforces the capsids structure. The reported binding of proteins UL17/UL25 to the pentamers of the A and C capsids seems the most likely candidate for such capsids strengthening. Finally, the data supports the view that initiation of DNA packaging triggers the maturation of HSV-1 capsids.

  11. Pain, Itch, Quality of Life, and Costs after Herpes Zoster.

    Science.gov (United States)

    van Wijck, Albert J M; Aerssens, Yannick R

    2017-07-01

    Herpes zoster (HZ) and postherpetic neuralgia are known to have a profound effect on the patient's quality of life, but the incidence and severity of itch and its relation with pain and quality of life in the long term are still relatively unknown. The aim of this study was to measure the presence and severity of pain and itch and impact on quality of life in patients over 50 years old with HZ. We enrolled 661 patients with HZ in this 12-month observational study. Patient data were collected via a web-based questionnaire. Outcomes were pain, itch, burden of illness, impact on patient's daily life, impact on quality of life, and healthcare costs. At inclusion, 94% of patients reported any pain, 74.3% significant pain, and 26% severe pain. After 3 months, 18.8% of patients suffered from postherpetic neuralgia. At inclusion, 70.8% of patients had any itch, 39.2% significant itch, and 7.3% severe itch. The occurrence of pain increases costs and has a high impact on the quality of life, lowering EQ-5D scores by an average of 18%. In contrast, itch has little effect on the quality of life. Pain and itch are highly prevalent months after HZ. Pain caused by HZ has a large impact on quality of life, burden of illness, impact on daily life, and health care costs for these patients. The impact of itch on quality of life is relatively small. © 2016 World Institute of Pain.

  12. Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication

    Science.gov (United States)

    Wang, Hong; Tollefson, Ann E.; Ying, Baoling; Korom, Maria; Cheng, Xiaohong; Cao, Feng; Davis, Katie L.; Wold, William S. M.

    2014-01-01

    Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 μM, with suppression at 50 μM reaching ∼1 million-fold. Five compounds in two chemical families inhibited HSV replication in Vero and human foreskin fibroblast cells as well as the approved drug acyclovir did. The compounds had 50% effective concentration values as low as 0.22 μM with negligible cytotoxicity in the assays employed. The inhibitors suppressed accumulation of viral genomes and infectious particles and blocked events in the viral replication cycle before and during viral DNA replication. Acyclovir-resistant mutants of HSV-1 and HSV-2 remained highly sensitive to the NTS inhibitors. Five of six NTS inhibitors of the HSVs also blocked replication of another herpesvirus pathogen, human cytomegalovirus. Therefore, NTS enzyme inhibitors are promising candidates for new herpesvirus treatments that may have broad efficacy against members of the herpesvirus family. PMID:25267681

  13. Higher Throughput Quantification of Neutralizing Antibody to Herpes Simplex Viruses.

    Science.gov (United States)

    Blevins, Tamara P; Mitchell, Michelle C; Korom, Maria; Wang, Hong; Yu, Yinyi; Morrison, Lynda A; Belshe, Robert B

    2015-01-01

    We report a rapid, higher throughput method for measuring neutralizing antibody to herpes simplex virus (HSV) in human sera. Clinical isolates and sera from the Herpevac Trial for Women were used in a colorimetric assay in which infection of tissue culture (lack of neutralization) was indicated by substrate metabolism by beta-galactosidase induced in the ELVIS cell line. The neutralization assay was optimized by addition of guinea pig complement, which particularly enhanced neutralizing antibody titers to HSV-2. Higher neutralizing antibody titers were also achieved using virus particles isolated from the supernatant of infected cells rather than lysate of infected cells as the source of virus. The effect of assay incubation time and incubation time with substrate were also optimized. We found that incubating with substrate until a standard optical density of 1.0 was reached permitted a better comparison among virus isolates, and achieved reliable measurement of neutralizing antibody activity. Interestingly, in contrast to results in the absence of complement, addition of complement allowed sera from HSV-2 gD-vaccinated subjects to neutralize HSV-1 and HSV-2 clinical and laboratory isolates with equal potency.

  14. Herpes Zoster Myelitis Presented with Brown-Sequard Syndrome

    Directory of Open Access Journals (Sweden)

    Ferah Kızılay

    2011-12-01

    Full Text Available Brown Séquard syndrome, is caused by a lesion effecting one half of the spinal cord in a segment or more than one segments. Below the lesion level, there is loss of deep sensory and motor functions on the ipsilateral side, whereas loss of pain and temparature sensations are present on the contralateral side. Most common causes are trauma, radiation necrosis and spinal metastases. Here, we aimed to present a case of herpes Zoster virus myelitis, that was presented as Brown Séquard sydrome, which is very rare. A 55-year-old male was presented with acute paresia of the right arm and leg. Three days after the start of these complaints, painful, itchy and vesicular blisters appeared on the extensor surface of the right arm. On neurological examination, there were 4+/5 paresis on the right arm and leg, loss of proprioception on the right upper and lower extremities, and loss of temparature sensation on the left upper and lower extremities. Servical MRI showed an expansile hyperintense lesion which was located on C5-C6 level within spinal cord, on T2-weighted images. Lesion diameter was 3 centimeters. Skin lesions showed regression within 15 days, whereas motor deficits remained stable. After 4 months, MRI showed marked regression of the spinal cord lesion. We aimed to share the findings of this HZV myelitis case, which is very rare and its MRI findings may easily misinterpreted as a spinal mass lesion

  15. Inhibition of multiplication of herpes simplex virus by caffeic acid.

    Science.gov (United States)

    Ikeda, Keiko; Tsujimoto, Kazuko; Uozaki, Misao; Nishide, Mitsunori; Suzuki, Yukiko; Koyama, A Hajime; Yamasaki, Hisashi

    2011-10-01

    Hot water extracts of coffee grinds and commercial instant coffee solutions have been shown to exhibit marked antiviral and virucidal activities against herpes simplex virus type 1 (HSV-1). Specifically, it has been shown that caffeine and N-methyl-pyridinium formate inhibit the multiplication of HSV-1 in HEp-2 cells. The present study examined the virological properties and the antiviral activity of caffeic acid against HSV-1. Caffeic acid inhibited the multiplication of HSV-1 in vitro, while chlorogenic acid, a caffeic acid ester with quinic acid, did not. These reagents did not have a direct virucidal effect. The one-step growth curve of HSV-1 showed that the addition of caffeic acid at 8 h post infection (h p.i.) did not significantly affect the formation of progeny viruses. An analysis of the influence of the time of caffeic acid addition, revealed that addition at an early time post infection remarkably inhibited the formation of progeny infectious virus in the infected cells, but its addition after 6 h p.i. (i.e., the time of the completion of viral genome replication) did not efficiently inhibit this process. These results indicate that caffeic acid inhibits HSV-1 multiplication mainly before the completion of viral DNA replication, but not thereafter. Although caffeic acid showed some cytotoxicity by prolonged incubation, the observed antiviral activity is likely not the secondary result of the cytotoxic effect of the reagent, because the inhibition of the virus multiplication was observed before appearance of the notable cytotoxicity.

  16. Ribonucleotides Linked to DNA of Herpes Simplex Virus Type 1

    Science.gov (United States)

    Hirsch, Ivan; Vonka, Vladimír

    1974-01-01

    Cells of a continuous cell line derived from rabbit embryo fibroblasts were infected with herpes simplex type 1 virus (HSV-1) and maintained in the presence of either [5-3H]uridine or [methyl-3H]thymidine or 32PO43−. Nucleocapsids were isolated from the cytoplasmic fraction, partially purified, and treated with DNase and RNase. From the pelleted nucleocapsids, DNA was extracted and purified by centrifugation in sucrose and cesium sulfate gradients. The acid-precipitable radioactivity of [5-3H]uridine-labeled DNA was partially susceptible to pancreatic RNase and alkaline treatment; the susceptibility to the enzyme decreased with increasing salt concentration. No drop of activity of DNA labeled with [3H]thymidine was observed either after RNase or alkali treatment. Base composition analysis of [5-3H]uridine-labeled DNA showed that the radioactivity was recovered as uracil and cytosine. In the cesium sulfate gradient, the purified [5-3H]uridine-labeled DNA banded at the same position as the 32P-labeled DNA. The present data tend to suggest that ribonucleotide sequences are present in HSV DNA, that they are covalently attached to the viral DNA, and that they can form double-stranded structures. PMID:4364894

  17. Overall and Comparative Risk of Herpes Zoster With Pharmacotherapy for Inflammatory Bowel Diseases: A Nationwide Cohort Study.

    Science.gov (United States)

    Khan, Nabeel; Patel, Dhruvan; Trivedi, Chinmay; Shah, Yash; Lichtenstein, Gary; Lewis, James; Yang, Yu-Xiao

    2018-01-05

    Patients with inflammatory bowel disease (IBD) might be at increased risk for herpes zoster infection. We sought to quantify the risk of herpes zoster in patients with IBD and evaluate the effects of IBD and IBD medications on the risk of herpes zoster. We conducted 2 retrospective studies of populations of Veterans, from January 2000 through June 2016. In study 1, we compared the incidence of herpes zoster among patients with IBD receiving 5-ASA alone vs matched patients without IBD. In study 2, we compared the incidence of herpes zoster among patients with IBD treated with only 5-ASA, with thiopurines, with antagonists of tumor necrosis factor (TNF), with a combination of thiopurines and TNF antagonists, and with vedolizumab. We used multivariable Cox regression to estimate the hazard ratios and 95% CIs for herpes zoster associated with IBD in study 1 and with different treatments in study 2. We also estimated the incidence rate of herpes zoster based on age and IBD medication subgroups. Compared to no IBD, ulcerative colitis (UC) and Crohn's disease (CD) were each associated with significantly increased risk of herpes zoster infection. In multivariable Cox regression (compared to no IBD), UC, CD, or IBD treated with 5-ASA treatment alone was associated with significantly increased risk of herpes zoster, with adjusted HRs (AHR) of 1.81 for UC (95% CI, 1.56-2.11), 1.56 for CD (95% CI, 1.28-1.91), and 1.72 for treated IBD (95% CI, 1.51-1.96). In multivariable Cox regression analysis, compared to exposure to 5-ASA alone, exposure to thiopurines (AHR, 1.47; 95% CI, 1.31-1.65) or a combination of thiopurines and TNF antagonists (AHR, 1.65; 95% CI, 1.22-2.23) was associated with increased risk of herpes zoster. However, exposure to TNF antagonists alone (AHR, 1.15; 95% CI, 0.96-1.38) was not associated with increased risk of herpes zoster. The incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the

  18. Mechanisms of sister chromatid recombination

    International Nuclear Information System (INIS)

    Nakai, Sayaka; Machida, Isamu; Tsuji, Satsuki

    1985-01-01

    Studies using T948 as a model system have been carried out aimed at elucidating the mechanism of sister chromatid recombination (SCR). Characterization of U.V. light- and x-ray-induced SCR, the relationiship between SCR induction and DNA repair using rad mutations, and the relationship between SCR induction and the time of cell division using cdc mutations are presented. It has been supposed that SCR is induced at the phase of S-G 2 following DNA replication, that postreplication break of DNA strands is strongly involved in the induction of SCR, and that induction type of SCR, i.e., conversion type or recombination type, is dependent upon the type of molecular damage of DNA. (Namekawa, K.)

  19. Heterogeneity in recombinant protein production

    DEFF Research Database (Denmark)

    Schalén, Martin; Johanson, Ted; Lundin, Luisa

    2012-01-01

    contribute to make a population in a fermenter heterogeneous, resulting in cell-to-cell variation in physiological parameters of the microbial culture. Our study aims at investigating how population heterogeneity and recombinant protein production is affected by environmental gradients in bioreactors....... For this purpose, a Saccharomyces cerevisiae strain, that functions as a protein production reporter, has been developed. A heterologous protein has been tagged with a fluorescent protein providing a way to measure the amount of heterologous protein produced by the cells on single cell level. Gradients...... are simulated in small bioreactors and the population heterogeneity can be visualised by analysing single cells with flow cytometry. This can give new insights to cell physiology and recombinant protein production at the industrial scale....

  20. Cell-mediated immunity to herpes simplex in humans: lymphocyte cytotoxicity measured by 51Cr release from infected cells

    International Nuclear Information System (INIS)

    Russell, A.S.; Percy, J.S.; Kovithavongs, T.

    1975-01-01

    We assessed cell-mediated immunity to herpes simplex virus type 1 antigen in patients suffering from recurrent cold sores and in a series of healthy controls. Paradoxically, all those subject to recurrent herpetic infections had, without exception, evidence of cell-mediated immunity to herpes antigens. This was demonstrated by lymphocyte transformation and specific 51 Cr release from infected human amnion cells after incubation with peripheral blood mononuclear cells. Where performed, skin tests with herpes antigen were also positive. In addition, serum from these patients specifically sensitized herpes virus-infected cells to killing by nonimmune, control mononuclear cells. These tests were negative in the control patients except in a few cases, and it is suggested that these latter may be the asymptomatic herpes virus carriers previously recognized or that they may have experienced a genital infection. (U.S.)