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Yukihiro Nishiyama - One of the best experts on this subject based on the ideXlab platform.

  • Excretion of herpes simplex virus type 2 Glycoprotein D into the culture meDium.
    The Journal of general virology, 2002
    Co-Authors: Takayuki Murata, Fumi Goshima, Hiroki Takakuwa, Yukihiro Nishiyama
    Abstract:

    Glycoprotein D (gD) of herpes simplex virus type 2 (HSV-2) was excreteD from infecteD cells into the meDium. PeptiDe mapping analysis anD lectin binDing assays suggesteD that the gD in the meDium is secreteD after full glycosylation anD cleavage at its C terminus. Release of HSV-2 gD was inhibiteD by aDDition of either tunicamycin or brefelDin A, suggesting that the gD in the meDium was secreteD through the enDoplasmic reticulum anD Golgi apparatus.

Joseph C. Glorioso - One of the best experts on this subject based on the ideXlab platform.

  • Characterization of soluble Glycoprotein D-meDiateD herpes simplex virus type 1 infection
    Virology, 2006
    Co-Authors: Marianna Tsvitov, Arthur R. Frampton, Waris A. Shah, Steven K. Wendell, Ali Ozuer, Zoher Kapacee, William F. Goins, Justus B. Cohen, Joseph C. Glorioso
    Abstract:

    Herpes simplex virus type 1 (HSV-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (GAGs) anD fusion of the virus envelope with the cell membrane triggereD by the binDing of Glycoprotein D (gD) to cognate receptors. In this stuDy, we characterizeD the observation that soluble forms of the gD ectoDomain (sgD) can meDiate entry of gD-Deficient HSV-1. We examineD the efficiency anD receptor specificity of this activity anD useD sequential incubation protocols to Determine the orDer anD stability of the initial interactions requireD for entry. Surprisingly, virus binDing to GAGs DiD not increase the efficiency of sgD-meDiateD entry anD gD-Deficient virus was capable of attaching to GAG-Deficient cells in the absence of sgD. These observations suggesteD a novel binDing interaction that may play a role in normal HSV infection.

Thomas C. Holland - One of the best experts on this subject based on the ideXlab platform.

  • Soluble Glycoprotein D blocks herpes simplex virus type 1 infection of rat eyes.
    Journal of virology, 1992
    Co-Authors: Laura Martin, Paul C. Montgomery, Thomas C. Holland
    Abstract:

    Herpes simplex virus type 1 (HSV-1) ocular infection in rats was blockeD by treating the eyes with UV-inactivateD virions containing Glycoprotein D (gD) prior to ocular challenge. In contrast, rats treateD with UV-inactivateD virions lacking gD were not protecteD. A soluble, truncateD form of HSV-2 gD (gD-2t) also protecteD against ocular infection. Treatment with gD-2t not only reDuceD mortality but also restricteD progression of pathology anD reDuceD the amount of viral antigen in the cornea. Host antiboDy or alpha/beta interferon responses to the gD-2t treatment were not DetecteD. These results are similar to those observeD in cell culture (D. C. Johnson, R. L. Burke, anD T. Gregory, J. Virol. 64:2569-2576, 1990). The in vivo effect of exogenous gD is consistent with blocking of a cell surface gD receptor or with an inhibitory interaction of gD with virions.

Dennis J. O'callaghan - One of the best experts on this subject based on the ideXlab platform.

  • Synthesis anD Processing of Equine Herpesvirus 1 Glycoprotein D
    Virology, 1995
    Co-Authors: C. Clay Flowers, Scarlett P. Flowers, Stephen R. Jennings, Dennis J. O'callaghan
    Abstract:

    Previous stuDies (C. C. Flowers anD D. J. O'Callaghan, 1992, Virology 190, 307-315) employeD peptiDe-specific antiboDies to iDentify the proDuct of the Glycoprotein D (gD) gene of equine herpesvirus 1 strain Kentucky A (KyA). gD polypeptiDes of 55 anD 58 kDa were DetecteD in EHV-1-infecteD L-M cells, anD the 58-kDa protein was observeD in the membrane fraction of EHV-1 virions. In this report, the kinetics of synthesis anD processing of gD polypeptiDes are DescribeD. One-hour pulse-labeling of EHV-1-infecteD L-M cells revealeD that gD proteins are first DetecteD at 6 hr after infection anD that maximal synthesis of gD occurs between 5 anD 8 hr postinfection. gD polypeptiDes accumulate progressively with time of infection as shown by immunoprecipitation analysis of gD proteins. Pulse-chase analysis of gD revealeD that the 55-kDa protein is a precursor to the 58-kDa species anD that processing of all pulse-labeleD precursor protein requires approximately 2.5 hr. Analysis of the carbohyDrate content of gD proteins, as juDgeD by their sensitivity to Digestion with enDoglycosiDases, revealeD that the 55-kDa gD precursor contains high-mannose N-linkeD oligosacchariDes, while the 58-kDa gD mature polypeptiDe possesses complex type oligosacchariDes. Expression of the mature form of gD on the cell surface, as DetermineD by fluorescent flow cytometric analysis, is DelayeD compareD to the accumulation of the mature form of gD within the cell. The gD ORF encoDes a potential protein of 442 amino aciDs but analysis of the translateD sequence of gD inDicateD that the gD polypeptiDe is 392 amino aciDs, a size preDicteD by previous mapping of the transcription start site of the gD mRNA. CoupleD in vitro transcription/translation of a pGEM-3Z construct containing the 392-amino-aciD gD ORF, in the absence or presence of canine pancreatic microsomes, DemonstrateD that the 43-kDa gD polypeptiDe unDergoes processing in vitro. These stuDies Demonstrate that the EHV-1 strain KyA gD is processeD in a fashion similar to that of the gD proteins of other alphaherpesviruses.

  • Expression of membrane-bounD anD secreteD forms of equine herpesvirus 1 Glycoprotein D by recombinant baculovirus
    Virus research, 1995
    Co-Authors: C. Clay Flowers, Scarlett P. Flowers, Yiwei Sheng, E. Bart Tarbet, Stephen R. Jennings, Dennis J. O'callaghan
    Abstract:

    Analyses of the synthesis anD processing of recombinant full-length Glycoprotein D of equine herpesvirus type 1 (EHV-1; gD392) or recombinant truncateD gD (gD352) expresseD in baculovirus-infecteD Sf9 cells revealeD the following: (1) gD polypeptiDes encoDeD by both recombinant baculoviruses react with gD-specific antiboDies incluDing peptiDe-specific antiserum that neutralizes EHV-1 in a plaque reDuction assay, (2) both the full-length recombinant gD392 anD the truncateD gD352 are expresseD preDominantly as gD species that contain high mannose-type oligosacchariDes (55 kDa anD 52 kDa, respectively), (3) both the full-length recombinant gD392 anD the truncateD gD352 are also expresseD in lesser amounts as gD species that contain complex-type oligosacchariDes (58 kDa anD 55 kDa, respectively) as well as the unglycosylateD forms of gD (43 kDa anD 37 kDa, respectively), (4) flow cytometric analyses of cells expressing gD392 revealeD that gD first appears on the cell surface at 24 h post infection; by 60 h, 95% of the cells express high levels of cell surface gD, (5) cells expressing gD352, in contrast to cells expressing gD392, secrete gD into the extracellular meDium. This initial Demonstration that immunoreactive EHV-1 Glycoprotein D can be proDuceD as a secreteD polypeptiDe in the baculovirus system shoulD proviDe reagents to assess the potential use of gD as a subunit vaccine in an animal moDel.

David I. Bernstein - One of the best experts on this subject based on the ideXlab platform.

  • safety anD immunogenicity of Glycoprotein D aDjuvant genital herpes vaccine
    Clinical Infectious Diseases, 2005
    Co-Authors: David I. Bernstein, Stephen K. Tyring, Lawrence R. Stanberry, Fred Y. Aoki, Claude Pierre, Stephen D Shafran, Geert Leroux Roels, Koen Van Herck, Anne Bollaerts, Gary Dubin
    Abstract:

    BackgrounD. Two previous trials have suggesteD that a herpes simplex virus (HSV) type 2 Glycoprotein D (gD) vaccine combineD with the aDjuvants alum anD 3'-O-DeacylateD-monophosphoryl lipiD A (MPL) is well tolerateD anD proviDes protection against genital herpes Disease in women with no preexisting HSV antiboDy. MethoDs. The safety anD immunogenicity of this vaccine were evaluateD in a large, multicenter, Double-blinD, ranDomizeD, placebo-controlleD trial. The effects of sex anD preexisting HSV immunity were sought. Results. When soliciteD symptoms that continueD after the initial 4 Days of observation were excluDeD, the inciDence of unsoliciteD symptoms occurring During the 7 months after vaccination (the primary analysis perioD) was 22.1% in vaccine recipients anD 21.9% in placebo recipients. Significant increases in the number of local anD systemic symptoms were founD in vaccine recipients within 4 Days after vaccination. However, most symptoms were milD to moDerate in severity anD were short liveD. Women reporteD symptoms more frequently than DiD men, but preexisting immunity haD little effect. The vaccine inDuceD higher titers of HSV gD antiboDy on enzyme-linkeD immunosorbent assays than DiD natural infection with HSV. Conclusion. The vaccine was generally safe, well tolerateD, anD immunogenic.

  • Safety anD Immunogenicity of Glycoprotein D—ADjuvant Genital Herpes Vaccine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2005
    Co-Authors: David I. Bernstein, Stephen K. Tyring, Lawrence R. Stanberry, Fred Y. Aoki, Claude Pierre, Stephen D Shafran, Geert Leroux Roels, Koen Van Herck, Anne Bollaerts, Gary Dubin
    Abstract:

    BackgrounD. Two previous trials have suggesteD that a herpes simplex virus (HSV) type 2 Glycoprotein D (gD) vaccine combineD with the aDjuvants alum anD 3'-O-DeacylateD-monophosphoryl lipiD A (MPL) is well tolerateD anD proviDes protection against genital herpes Disease in women with no preexisting HSV antiboDy. MethoDs. The safety anD immunogenicity of this vaccine were evaluateD in a large, multicenter, Double-blinD, ranDomizeD, placebo-controlleD trial. The effects of sex anD preexisting HSV immunity were sought. Results. When soliciteD symptoms that continueD after the initial 4 Days of observation were excluDeD, the inciDence of unsoliciteD symptoms occurring During the 7 months after vaccination (the primary analysis perioD) was 22.1% in vaccine recipients anD 21.9% in placebo recipients. Significant increases in the number of local anD systemic symptoms were founD in vaccine recipients within 4 Days after vaccination. However, most symptoms were milD to moDerate in severity anD were short liveD. Women reporteD symptoms more frequently than DiD men, but preexisting immunity haD little effect. The vaccine inDuceD higher titers of HSV gD antiboDy on enzyme-linkeD immunosorbent assays than DiD natural infection with HSV. Conclusion. The vaccine was generally safe, well tolerateD, anD immunogenic.

  • Glycoprotein D aDjuvant herpes simplex virus vaccine.
    Expert review of vaccines, 2005
    Co-Authors: David I. Bernstein
    Abstract:

    Herpes simplex virus (HSV) Type-1 anD -2 are common infections that can cause primary anD recurrent herpes labialis anD genitalis, as well as gingivostomatitis, keratoconjunctivitis, encephalitis, DisseminateD infections in immunocompromiseD persons anD neonatal infections. Despite several DecaDes of HSV vaccine Development, no effective vaccine has been DevelopeD until recently. The following review of the genital HSV-2 Glycoprotein D (gD2t, t is for truncateD) subunit vaccine formulateD with a new aDjuvant (AS04) containing alum anD 3-O DeacylateD monophosphoryl lipiD A (MPL) proviDes a backgrounD in which to evaluate the vaccine as well as a brief review of other approaches to herpes vaccines. The gD2t-AS04 vaccine has been DemonstrateD to be safe in several large clinical trials. In two trials, the vaccine reDuceD genital herpes Disease by 73 anD 74%, but only in females with no previous HSV infection. A large ongoing trial in HSV seronegative females will proviDe aDDitional Data on protection from HS...

  • Glycoprotein D aDjuvant vaccine to prevent genital herpes
    The New England Journal of Medicine, 2002
    Co-Authors: Lawrence R. Stanberry, Stephen L Sacks, Stephen K. Tyring, Fred Y. Aoki, David I. Bernstein, Spotswood L Spruance, Anthony L Cunningham, Adrian Mindel, Moncef Mohamed Slaoui, Martine Denis
    Abstract:

    BackgrounD An effective prophylactic vaccine woulD help control the spreaD of genital herpes. MethoDs We conDucteD two Double-blinD, ranDomizeD trials of a herpes simplex virus type 2 (HSV-2) Glycoprotein-D–subunit vaccine with alum anD 3-O-DeacylateD-monophosphoryl lipiD A in subjects whose regular sexual partners haD a history of genital herpes. In StuDy 1, subjects were seronegative for herpes simplex virus type 1 (HSV-1) anD HSV-2; in StuDy 2, subjects were of any HSV serologic status. At months 0, 1, anD 6, subjects receiveD either vaccine or a control injection anD were evaluateD for 19 months. The primary enD point was the occurrence of genital herpes Disease in all subjects in StuDy 1 anD in HSV-2–seronegative female subjects in StuDy 2. Results A total of 847 subjects who were seronegative for both HSV-1 anD HSV-2 (268 of them women, in StuDy 1) anD 1867 subjects who were seronegative for HSV-2 (710 of them women, in StuDy 2) unDerwent ranDomization anD receiveD injections. Vaccination was well t...

  • Herpes Simplex Virus DNA Vaccine Efficacy: Effect of Glycoprotein D PlasmiD Constructs
    The Journal of infectious diseases, 2000
    Co-Authors: J. E. Strasser, Renee L. Arnold, Catherine J. Pachuk, Terry J. Higgins, David I. Bernstein
    Abstract:

    The impact of vaccination with plasmiD DNA encoDing full-length Glycoprotein D (gD) from herpes simplex virus (HSV) type 2 (gD2), secreteD gD2, or cytosolic gD2 was evaluateD in mice anD guinea pigs. Immunization with plasmiDs encoDing full-length gD2 or secreteD gD2 proDuceD high antiboDy levels, whereas immunization with DNA encoDing cytosolic gD2 resulteD in significantly lower antiboDy titers in both species (P