Impact of valency of a glycoprotein B-specific monoclonal antibody on neutralization of herpes simplex virus.


:Herpes simplex virus (HSV) glycoprotein B (gB) is an integral part of the multicomponent fusion system required for virus entry and cell-cell fusion. Here we investigated the mechanism of viral neutralization by the monoclonal antibody (MAb) 2c, which specifically recognizes the gB of HSV type 1 (HSV-1) and HSV-2. Binding of MAb 2c to a type-common discontinuous epitope of gB resulted in highly efficient neutralization of HSV at the postbinding/prefusion stage and completely abrogated the viral cell-to-cell spread in vitro. Mapping of the antigenic site recognized by MAb 2c to the recently solved crystal structure of the HSV-1 gB ectodomain revealed that its discontinuous epitope is only partially accessible within the observed multidomain trimer conformation of gB, likely representing its postfusion conformation. To investigate how MAb 2c may interact with gB during membrane fusion, we characterized the properties of monovalent (Fab and scFv) and bivalent [IgG and F(ab')(2)] derivatives of MAb 2c. Our data show that the neutralization capacity of MAb 2c is dependent on cross-linkage of gB trimers. As a result, only bivalent derivatives of MAb 2c exhibited high neutralizing activity in vitro. Notably, bivalent MAb 2c not only was capable of preventing mucocutaneous disease in severely immunodeficient NOD/SCID mice upon vaginal HSV-1 challenge but also protected animals even with neuronal HSV infection. We also report for the first time that an anti-gB specific monoclonal antibody prevents HSV-1-induced encephalitis entirely independently from complement activation, antibody-dependent cellular cytotoxicity, and cellular immunity. This indicates the potential for further development of MAb 2c as an anti-HSV drug.


J Virol


Journal of virology


Krawczyk A,Krauss J,Eis-Hübinger AM,Däumer MP,Schwarzenbacher R,Dittmer U,Schneweis KE,Jäger D,Roggendorf M,Arndt MA




Has Abstract


2011-02-01 00:00:00














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    abstract::The primary herpes simplex virus type 2 (HSV-2) latency-associated transcript (LAT) promoter influences LAT expression and rates of virus reactivation. We explored the biological importance of particular neuronally responsive regions within the promoter by creating new recombinant viruses bearing a targeted deletion (...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Wang K,Pesnicak L,Straus SE

    更新日期:1997-10-01 00:00:00

  • Systematic assembly of a full-length infectious clone of human coronavirus NL63.

    abstract::Historically, coronaviruses were predominantly associated with mild upper respiratory disease in humans. More recently, three novel coronaviruses associated with severe human respiratory disease were found, including (i) the severe acute respiratory syndrome coronavirus, associated with a significant atypical pneumoni...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Donaldson EF,Yount B,Sims AC,Burkett S,Pickles RJ,Baric RS

    更新日期:2008-12-01 00:00:00

  • Human cytomegalovirus tegument protein pp71 (ppUL82) enhances the infectivity of viral DNA and accelerates the infectious cycle.

    abstract::Three tegument proteins of human cytomegalovirus (HCMV), ppUL82 (pp71), pUL69, and ppUL83 (pp65), were examined for the ability to stimulate the production of infectious virus from human diploid fibroblasts transfected with viral DNA. Although viral DNA alone had a low intrinsic infectivity of 3 to 8 plaques/microg of...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Baldick CJ Jr,Marchini A,Patterson CE,Shenk T

    更新日期:1997-06-01 00:00:00

  • The Antagonism of HIV-1 Nef to SERINC5 Particle Infectivity Restriction Involves the Counteraction of Virion-Associated Pools of the Restriction Factor.

    abstract::SERINC3 (serine incorporator 3) and SERINC5 are recently identified host cell inhibitors of HIV-1 particle infectivity that are counteracted by the viral pathogenesis factor Nef. Here we confirm that HIV-1 Nef, but not HIV-1 Vpu, antagonizes the particle infectivity restriction of SERINC5. SERINC5 antagonism occurred ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Trautz B,Pierini V,Wombacher R,Stolp B,Chase AJ,Pizzato M,Fackler OT

    更新日期:2016-11-14 00:00:00

  • Isolation of a transcriptive complex from Newcastle disease virions.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Colonno RJ,Stone HO

    更新日期:1976-09-01 00:00:00

  • Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV.

    abstract::Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Ourmanov I,Brown CR,Moss B,Carroll M,Wyatt L,Pletneva L,Goldstein S,Venzon D,Hirsch VM

    更新日期:2000-03-01 00:00:00

  • 7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kopecky-Bromberg SA,Martinez-Sobrido L,Palese P

    更新日期:2006-01-01 00:00:00

  • Evolution of defective-interfering double-stranded RNAs of the yeast killer virus.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Kane WP,Pietras DF,Bruenn JA

    更新日期:1979-11-01 00:00:00

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Wetzel JD,Wilson GJ,Baer GS,Dunnigan LR,Wright JP,Tang DS,Dermody TS

    更新日期:1997-02-01 00:00:00

  • Asymmetric transcription of mouse mammary tumor virus genes in vivo and in vitro.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Prewitt RS,Washington LD,Stallcup MR

    更新日期:1984-04-01 00:00:00

  • Cytomegalovirus encodes a positive regulator of antigen presentation.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Holtappels R,Gillert-Marien D,Thomas D,Podlech J,Deegen P,Herter S,Oehrlein-Karpi SA,Strand D,Wagner M,Reddehase MJ

    更新日期:2006-08-01 00:00:00

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Pugatsch T,Stacey DW

    更新日期:1982-08-01 00:00:00

  • Twin studies demonstrate a host cell genetic effect on productive human immunodeficiency virus infection of human monocytes and macrophages in vitro.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Chang J,Naif HM,Li S,Sullivan JS,Randle CM,Cunningham AL

    更新日期:1996-11-01 00:00:00

  • Mitochondrion-enriched anionic phospholipids facilitate flock house virus RNA polymerase membrane association.

    abstract::One characteristic of all positive-strand RNA viruses is the necessity to assemble viral RNA replication complexes on host intracellular membranes, a process whose molecular details are poorly understood. To study viral replication complex assembly we use the established model system of Flock House virus (FHV), which ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Stapleford KA,Rapaport D,Miller DJ

    更新日期:2009-05-01 00:00:00

  • Immunoglobulin with High-Titer In Vitro Cross-Neutralizing Hepatitis C Virus Antibodies Passively Protects Chimpanzees from Homologous, but Not Heterologous, Challenge.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Bukh J,Engle RE,Faulk K,Wang RY,Farci P,Alter HJ,Purcell RH

    更新日期:2015-09-01 00:00:00

  • Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Arndt WD,Cotsmire S,Trainor K,Harrington H,Hauns K,Kibler KV,Huynh TP,Jacobs BL

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  • Characterization of DNA sequence-common and sequence-specific proteins binding to cis-acting sites for cleavage of the terminal a sequence of the herpes simplex virus 1 genome.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Chou J,Roizman B

    更新日期:1989-03-01 00:00:00

  • Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity.

    abstract::The cytotoxic T-lymphocyte (CTL) response to lymphocytic choriomeningitis virus infection determines the outcome of infection. Here we show that this response in BALB/c mice (H-2d), when analyzed both at the primary CTL level and using CTL clones, is predominantly monospecific. The vast majority of CTL have a common s...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Whitton JL,Tishon A,Lewicki H,Gebhard J,Cook T,Salvato M,Joly E,Oldstone MB

    更新日期:1989-10-01 00:00:00

  • Clink, a nanovirus-encoded protein, binds both pRB and SKP1.

    abstract::Clink, a 20-kDa protein of faba bean necrotic yellows virus, a single-stranded DNA plant virus, interacts with pRB family members and a SKP1 homologue from Medicago sativa. An LxCxE motif and an F-box of Clink mediate the interactions with the respective proteins. The capacity of Clink to bind pRB correlates with its ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Aronson MN,Meyer AD,Györgyey J,Katul L,Vetten HJ,Gronenborn B,Timchenko T

    更新日期:2000-04-01 00:00:00

  • Sindbis virus proteins nsP1 and nsP2 contain homology to nonstructural proteins from several RNA plant viruses.

    abstract::Although the genetic organization of tobacco mosaic virus (TMV) differs considerably from that of the tripartite viruses (alfalfa mosaic virus [AlMV] and brome mosaic virus [BMV]), all of these RNA plant viruses share three domains of homology among their nonstructural proteins. One such domain, common to the AlMV and...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Ahlquist P,Strauss EG,Rice CM,Strauss JH,Haseloff J,Zimmern D

    更新日期:1985-02-01 00:00:00

  • Structure of varicella-zoster virus DNA.

    abstract::Varicella-zoster virus (VZV) DNA was prepared from nucleocapsids and from enveloped virions of a laboratory strain (Ellen) and directly from the vesicle fluids of patients with zoster infections. VZV Ellen nucleocapsid DNA was cleaved with 11 different restriction endonucleases and electrophoresed in agarose gels. The...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Straus SE,Aulakh HS,Ruyechan WT,Hay J,Casey TA,Vande Woude GF,Owens J,Smith HA

    更新日期:1981-11-01 00:00:00

  • Marek's disease herpesviruses. IV. Molecular characterization of Marek's disease herpesvirus A antigen.

    abstract::Marek's disease herpesvirus A antigen (MDHV-A) was identified as a 61,000- to 65,000-dalton glycoprotein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after immunoprecipitation from the culture medium of both [35S]methionine- and [14C]glucosamine-labeled infected cells by specific rabbit serum directed ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Glaubiger C,Nazerian K,Velicer LF

    更新日期:1983-03-01 00:00:00

  • Blue native PAGE and biomolecular complementation reveal a tetrameric or higher-order oligomer organization of the physiological measles virus attachment protein H.

    abstract::Members of the Paramyxovirinae subfamily rely on the concerted action of two envelope glycoprotein complexes, attachment protein H and the fusion (F) protein oligomer, to achieve membrane fusion for viral entry. Despite advances in X-ray information, the organization of the physiological attachment (H) oligomer in fun...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Brindley MA,Plemper RK

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  • tRNA's associated with the 70S RNA of avian myeloblastosis virus.

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Waters LC,Mullin BC,Bailiff EG,Popp RA

    更新日期:1975-12-01 00:00:00

  • Intracellular inclusions resulting from infection with African horsesickness virus.

    abstract::Intranuclear and intracytoplasmic inclusions in monkey kidney cells infected with African horsesickness virus were studied with the aid of electron microscopy. ...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Breese SS Jr,Ozawa Y

    更新日期:1969-07-01 00:00:00

  • Transcription factor AP-1 modulates the activity of the human foamy virus long terminal repeat.

    abstract::The human foamy virus (HFV) contains within the U3 region of its long terminal repeat (LTR) three perfect consensus sequences for the binding of the inducible transcription factor AP-1. Results of DNase I footprint protection and gel retardation assays demonstrated that proteins in extracts of HeLa and BHK-21 cells as...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Maurer B,Serfling E,ter Meulen V,Rethwilm A

    更新日期:1991-11-01 00:00:00

  • Partial molecular characterization of two simian immunodeficiency viruses (SIV) from African colobids: SIVwrc from Western red colobus (Piliocolobus badius) and SIVolc from olive colobus (Procolobus verus).

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    pub_type: 杂志文章


    authors: Courgnaud V,Formenty P,Akoua-Koffi C,Noe R,Boesch C,Delaporte E,Peeters M

    更新日期:2003-01-01 00:00:00

  • Rotavirus NSP5: mapping phosphorylation sites and kinase activation and viroplasm localization domains.

    abstract::Rotavirus NSP5 is a nonstructural protein that localizes in cytoplasmic viroplasms of infected cells. NSP5 interacts with NSP2 and undergoes a complex posttranslational hyperphosphorylation, generating species with reduced polyacrylamide gel electrophoresis mobility. This process has been suggested to be due in part t...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Eichwald C,Vascotto F,Fabbretti E,Burrone OR

    更新日期:2002-04-01 00:00:00

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    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Siu YT,Chin KT,Siu KL,Yee Wai Choy E,Jeang KT,Jin DY

    更新日期:2006-07-01 00:00:00

  • Simian virus 40 small-t does not transactivate RNA polymerase II promoters in virus infections.

    abstract::Transcriptional stimulatory properties of virus-encoded transactivators appear to be critical for viral gene expression and may be linked to cellular transformation in certain cases. Recently, the simian virus 40 (SV40) 17-kDa small-t antigen was shown to stimulate transcription of polymerase II and III genes in trans...

    journal_title:Journal of virology

    pub_type: 杂志文章


    authors: Rajan P,Dhamankar V,Rundell K,Thimmapaya B

    更新日期:1991-12-01 00:00:00