Mapping a neutralizing epitope onto the capsid of adeno-associated virus serotype 8.

Abstract:

:Adeno-associated viruses (AAVs) are small single-stranded DNA viruses that can package and deliver nongenomic DNA for therapeutic gene delivery. AAV8, a liver-tropic vector, has shown great promise for the treatment of hemophilia A and B. However, as with other AAV vectors, host anti-capsid immune responses are a deterrent to therapeutic success. To characterize the antigenic structure of this vector, cryo-electron microscopy and image reconstruction (cryo-reconstruction) combined with molecular genetics, biochemistry, and in vivo approaches were used to define an antigenic epitope on the AAV8 capsid surface for a neutralizing monoclonal antibody, ADK8. Docking of the crystal structures of AAV8 and a generic Fab into the cryo-reconstruction for the AAV8-ADK8 complex identified a footprint on the prominent protrusions that flank the 3-fold axes of the icosahedrally symmetric capsid. Mutagenesis and cell-binding studies, along with in vitro and in vivo transduction assays, showed that the major ADK8 epitope is formed by an AAV variable region, VRVIII (amino acids 586 to 591 [AAV8 VP1 numbering]), which lies on the surface of the protrusions facing the 3-fold axis. This region plays a role in AAV2 and AAV8 cellular transduction. Coincidently, cell binding and trafficking assays indicate that ADK8 affects a postentry step required for successful virus trafficking to the nucleus, suggesting a probable mechanism of neutralization. This structure-directed strategy for characterizing the antigenic regions of AAVs can thus generate useful information to help re-engineer vectors that escape host neutralization and are hence more efficacious.

journal_name

J Virol

journal_title

Journal of virology

authors

Gurda BL,Raupp C,Popa-Wagner R,Naumer M,Olson NH,Ng R,McKenna R,Baker TS,Kleinschmidt JA,Agbandje-McKenna M

doi

10.1128/JVI.00218-12

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

7739-51

issue

15

eissn

0022-538X

issn

1098-5514

pii

JVI.00218-12

journal_volume

86

pub_type

杂志文章
  • RNA polymerase II is aberrantly phosphorylated and localized to viral replication compartments following herpes simplex virus infection.

    abstract::During lytic infection, herpes simplex virus subverts the host cell RNA polymerase II transcription machinery to efficiently express its own genome while repressing the expression of most cellular genes. The mechanism by which RNA polymerase II is directed to the viral delayed-early and late genes is still unresolved....

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.68.2.988-1001.1994

    authors: Rice SA,Long MC,Lam V,Spencer CA

    更新日期:1994-02-01 00:00:00

  • Cottontail rabbit papillomavirus E8 protein is essential for wart formation and provides new insights into viral pathogenesis.

    abstract::The cottontail rabbit papillomavirus (CRPV) a and b subtypes display a conserved E8 open reading frame encoding a 50-amino-acid hydrophobic protein, with structural similarities to the E5 transmembrane oncoprotein of genital human PVs (HPVs). CRPV E8 has been reported to play a role in papilloma growth but not to be e...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.80.10.4890-4900.2006

    authors: Nonnenmacher M,Salmon J,Jacob Y,Orth G,Breitburd F

    更新日期:2006-05-01 00:00:00

  • Fate of infecting simian virus 40-deoxyribonucleic acid in nonpermissive cells: integration into host deoxyribonucleic acid.

    abstract::Nonpermissive 3T3 cells were infected with purified superhelical simian virus 40 (SV40) deoxyribonucleic acid I (DNA I). One hour after infection, approximately 60% of the intracellular SV40 DNA was converted to relaxed forms. One day after infection, all intracellular SV40 DNA was present as slow-sedimenting material...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.10.3.425-432.1972

    authors: Collins CJ,Sauer G

    更新日期:1972-09-01 00:00:00

  • Increased rate of RNA synthesis: early reaction of primary mouse kidney cells to infection with polyoma virus of simian virus 40.

    abstract::The rate of transcription in isolated nuclei of primary mouse kidney cells increases by a factor of about 1.5 between 5 and 8 h after infection with polyoma virus or simian virus 40. This process requires intact virus and is inhibited by cycloheximide and actinomycin D. It appears to involve the activity of all three ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.35.1.8-19.1980

    authors: Pöckl E,Wintersberger E

    更新日期:1980-07-01 00:00:00

  • Pattern recognition receptor MDA5 modulates CD8+ T cell-dependent clearance of West Nile virus from the central nervous system.

    abstract::Many viruses induce type I interferon responses by activating cytoplasmic RNA sensors, including the RIG-I-like receptors (RLRs). Although two members of the RLR family, RIG-I and MDA5, have been implicated in host control of virus infection, the relative role of each RLR in restricting pathogenesis in vivo remains un...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01403-13

    authors: Lazear HM,Pinto AK,Ramos HJ,Vick SC,Shrestha B,Suthar MS,Gale M Jr,Diamond MS

    更新日期:2013-11-01 00:00:00

  • Analysis of antigenic determinants of structural polypeptides of avian type C tumor viruses.

    abstract::Radioimmunoassays were developed for the 19,000, 15,000, and 12,000 molecular weight polypeptides of avian myeloblastosis virus and for the 19,000 and 12,000 polypeptides of RAV-0, a subgroup E avian tumor virus. Each polypeptide was shown to possess both group- and type-specific antigenic determinants, in contrast to...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.16.1.27-33.1975

    authors: Stephenson JR,Smith EJ,Crittenden LB,Aaronson SA

    更新日期:1975-07-01 00:00:00

  • Nonviable mutants of simian virus 40 with deletions near the 3' end of gene A define a function for large T antigen required after onset of viral DNA replication.

    abstract::Deletion mutants of simian virus 40 (SV40) with lesions at the three DdeI sites near the 3' end of the early region were constructed. Mutants with deletions at 0.203 and 0.219 map units (mu) which did not change the large T antigen reading frame were viable. This extends slightly the upstream boundary for the location...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.47.3.487-494.1983

    authors: Tornow J,Cole CN

    更新日期:1983-09-01 00:00:00

  • tat Exon 1 exhibits functional diversity during HIV-1 subtype C primary infection.

    abstract::Human immunodeficiency virus type 1 (HIV-1) Tat is a mediator of viral transcription and is involved in the control of virus replication. However, associations between HIV-1 Tat diversity and functional effects during primary HIV-1 infection are still unclear. We estimated selection pressures in tat exon 1 using the m...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.03297-12

    authors: Rossenkhan R,MacLeod IJ,Sebunya TK,Castro-Nallar E,McLane MF,Musonda R,Gashe BA,Novitsky V,Essex M

    更新日期:2013-05-01 00:00:00

  • Identification of a new neutralization antigenic site on poliovirus coat protein VP2.

    abstract::Major neutralization antigenic sites have been previously mapped by us on VP1, the largest capsid protein of poliovirus type 1. Here we report the first identification of the primary sequence of a neutralization antigenic site on capsid protein VP2. Inspection of the amino acid sequence of VP2 led to the selection and...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.52.2.719-721.1984

    authors: Emini EA,Jameson BA,Wimmer E

    更新日期:1984-11-01 00:00:00

  • Restrictions to the adaptation of influenza a virus h5 hemagglutinin to the human host.

    abstract::The binding specificities of a panel of avian influenza virus subtype H5 hemagglutinin (HA) proteins bearing mutations at key residues in the receptor binding site were investigated. The results demonstrate that two simultaneous mutations in the receptor binding site resulted in H5 HA binding in a pattern similar to t...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.78.1.502-507.2004

    authors: Harvey R,Martin AC,Zambon M,Barclay WS

    更新日期:2004-01-01 00:00:00

  • Inhibition of interferon signaling by the Kaposi's sarcoma-associated herpesvirus full-length viral interferon regulatory factor 2 protein.

    abstract::Interferon (IFN) signal transduction involves interferon regulatory factors (IRF). Kaposi's sarcoma-associated herpesvirus (KSHV) encodes four IRF homologues: viral IRF 1 (vIRF-1) to vIRF-4. Previous functional studies revealed that the first exon of vIRF-2 inhibited alpha/beta interferon (IFN-alpha/beta) signaling. W...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.80.6.3092-3097.2006

    authors: Fuld S,Cunningham C,Klucher K,Davison AJ,Blackbourn DJ

    更新日期:2006-03-01 00:00:00

  • Second-site long terminal repeat (LTR) revertants of replication-defective human immunodeficiency virus: effects of revertant TATA box motifs on virus infectivity, LTR-directed expression, in vitro RNA synthesis, and binding of basal transcription factors

    abstract::Second-site revertants from replication-incompetent molecular clones of human immunodeficiency virus (HIV) contain base substitutions adjacent to the TATA motif. The altered TATA box motifs were analyzed for their effect(s) on virus infectivity, long terminal repeat (LTR)-directed expression in transient transfection ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.68.5.3298-3307.1994

    authors: Kashanchi F,Shibata R,Ross EK,Brady JN,Martin MA

    更新日期:1994-05-01 00:00:00

  • Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity.

    abstract::Accurate and sensitive quantitation of infectious human immunodeficiency virus (HIV) has been difficult to achieve. In this report, a quantitative focal immunoassay (FIA) for HIV was developed using human HeLa cells rendered susceptible to HIV infection by introduction of the CD4 gene via a retrovirus vector. Infected...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.62.10.3779-3788.1988

    authors: Chesebro B,Wehrly K

    更新日期:1988-10-01 00:00:00

  • Identification of Antinorovirus Genes in Human Cells Using Genome-Wide CRISPR Activation Screening.

    abstract::Noroviruses (NoVs) are a leading cause of gastroenteritis worldwide, yet host factors that restrict NoV replication are not well understood. Here, we use a CRISPR activation genome-wide screening to identify host genes that can inhibit murine norovirus (MNoV) replication in human cells. Our screens identified with hig...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01324-18

    authors: Orchard RC,Sullender ME,Dunlap BF,Balce DR,Doench JG,Virgin HW

    更新日期:2018-12-10 00:00:00

  • The Coxsackievirus and Adenovirus Receptor, a Required Host Factor for Recovirus Infection, Is a Putative Enteric Calicivirus Receptor.

    abstract::Human norovirus (HuNoV) is a leading cause of acute gastroenteritis in both developed and developing countries. Studies of HuNoV host cell interactions are limited by the lack of a simple, robust cell culture system. Due to their diverse HuNoV-like biological features, including histo-blood group antigen (HBGA) bindin...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00869-19

    authors: Farkas T,Yang K,Le Pendu J,Baines JD,Cardin RD

    更新日期:2019-10-29 00:00:00

  • Respiratory syncytial virus infection in C57BL/6 mice: clearance of virus from the lungs with virus-specific cytotoxic T cells.

    abstract::We describe respiratory syncytial virus (RSV)-specific cytotoxic T-cell (CTL) lines and clones developed from the spleens of C57BL/6 and BALB/c mice. Line 7 and clones derived from it were H-2Kb restricted, whereas line 12 had both Kb and Db components. Both lines, and all the clones except one, could lyse targets inf...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.65.8.4494-4497.1991

    authors: Muñoz JL,McCarthy CA,Clark ME,Hall CB

    更新日期:1991-08-01 00:00:00

  • Genetic informational RNA is not required for recombinant prion infectivity.

    abstract::Whether a genetic informational nucleic acid is required for the infectivity of transmissible spongiform encephalopathies is central to the debate about the infectious agent. Here we report that an infectious prion formed with bacterially expressed recombinant prion protein plus synthetic polyriboadenylic acid and syn...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.06216-11

    authors: Wang F,Zhang Z,Wang X,Li J,Zha L,Yuan CG,Weissmann C,Ma J

    更新日期:2012-02-01 00:00:00

  • CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo.

    abstract::The innate and adaptive immune responses have evolved distinct strategies for controlling different viral pathogens. Encephalomyocarditis virus (EMCV) is a picornavirus that can cause paralysis, diabetes, and myocarditis within days of infection. The optimal innate immune response against EMCV in vivo requires CD1d. I...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02745-05

    authors: Ilyinskii PO,Wang R,Balk SP,Exley MA

    更新日期:2006-07-01 00:00:00

  • Marker rescue of temperature-sensitive mutations of vaccinia virus WR: correlation of genetic and physical maps.

    abstract::The physical map locations of 62 temperature-sensitive mutations of vaccinia virus WR have been determined by marker rescue experiments, using cloned HindIII fragments of wild-type DNA. Since vaccinia virus DNA is not infectious, marker rescue was performed by infecting monolayers of cells at the nonpermissive tempera...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.48.2.419-428.1983

    authors: Ensinger MJ,Rovinsky M

    更新日期:1983-11-01 00:00:00

  • Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread.

    abstract::Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01492-10

    authors: Lin LT,Chen TY,Chung CY,Noyce RS,Grindley TB,McCormick C,Lin TC,Wang GH,Lin CC,Richardson CD

    更新日期:2011-05-01 00:00:00

  • Multiple viral determinants mediate myopathogenicity in coxsackievirus B1-induced chronic inflammatory myopathy.

    abstract::Mice infected with myopathic coxsackievirus B1 Tucson (CVB1(T)) develop chronic inflammatory myopathy (CIM) consisting of hind limb weakness and inflammation. Amyopathic virus variants are infectious but attenuated for CIM. In this report, viral clones, chimeras, and sequencing were used to identify viral determinants...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.77.21.11849-11854.2003

    authors: Tam PE,Weber-Sanders ML,Messner RP

    更新日期:2003-11-01 00:00:00

  • Interferon structural genes do not participate in quantitative regulation of interferon production by If loci as shown in C57BL/6 mice that are congenic with BALB/c mice at the alpha interferon gene cluster.

    abstract::Previous studies have shown that serum interferon (IFN) production in mice is quantitatively influenced by If loci, whose alleles determine high or low production. Although different loci influence IFN production in response to different inducers, such as Newcastle disease virus, Sendai virus, herpes simplex virus typ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.58.3.743-747.1986

    authors: De Maeyer-Guignard J,Dandoy F,Bailey DW,De Maeyer E

    更新日期:1986-06-01 00:00:00

  • Dengue virus inhibits the production of type I interferon in primary human dendritic cells.

    abstract::Dengue virus (DENV) infects human immune cells in vitro and likely infects dendritic cells (DCs) in vivo. DENV-2 productive infection induces activation and release of high levels of chemokines and proinflammatory cytokines in monocyte-derived DCs (moDCs), with the notable exception of alpha/beta interferon (IFN-alpha...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02514-09

    authors: Rodriguez-Madoz JR,Bernal-Rubio D,Kaminski D,Boyd K,Fernandez-Sesma A

    更新日期:2010-05-01 00:00:00

  • Regulation of protein synthesis in vesicular stomatitis virus-infected mouse L-929 cells by decreased protein synthesis initiation factor 2 activity.

    abstract::Infection of mouse L-cell spinner cultures by vesicular stomatitis virus (VSV) effected the selective translation of viral mRNA by 4h after viral adsorption. Cell-free systems prepared from mock- and VSV-infected cells reflected this phenomenon; protein synthesis was reduced in the virus-infected cell lysate by approx...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.41.3.781-791.1982

    authors: Centrella M,Lucas-Lenard J

    更新日期:1982-03-01 00:00:00

  • Expression pattern of mouse mammary tumor virus in transgenic mice carrying exogenous proviruses of different origins.

    abstract::To study the tissue specificity of mouse mammary tumor virus (MMTV) gene expression, we developed two series of transgenic mice, containing the MMTV proviral DNA of mammary (GR) and kidney (C3H-K) origin. The expression pattern in the MMTV(GR) transgenic mice is very similar to that observed in infected animals, e.g.,...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.66.7.4580-4586.1992

    authors: Rollini P,Billotte J,Kolb E,Diggelmann H

    更新日期:1992-07-01 00:00:00

  • Adeno-associated virus site-specific integration is regulated by TRP-185.

    abstract::Adeno-associated virus (AAV) integrates site specifically into the AAVS1 locus on human chromosome 19. Although recruitment of the AAV nonstructural protein Rep78/68 to the Rep binding site (RBS) on AAVS1 is thought to be an essential step, the mechanism of the site-specific integration, particularly, how the site of ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02014-06

    authors: Yamamoto N,Suzuki M,Kawano MA,Inoue T,Takahashi RU,Tsukamoto H,Enomoto T,Yamaguchi Y,Wada T,Handa H

    更新日期:2007-02-01 00:00:00

  • Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells.

    abstract::A continuous cell line of highly contact-inhibited cells (NIH/3T3) has been developed from NIH Swiss mouse embryo cultures. Its growth properties are similar to those of 3T3 and BALB/3T3. Although 3T3 is relatively insensitive to focus formation by murine sarcoma viruses, cloned lines of both NIH/3T3 and BALB/3T3 have...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.4.5.549-553.1969

    authors: Jainchill JL,Aaronson SA,Todaro GJ

    更新日期:1969-11-01 00:00:00

  • The Epstein-Barr virus major latent promoter Qp is constitutively active, hypomethylated, and methylation sensitive.

    abstract::Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is indispensable for viral DNA replication and episome maintenance in latency. Four promoters, Cp, Wp, Qp, and Fp, are known to drive EBNA1 expression. Here we show that the TATA-less Qp is constitutively active in a variety of EBV-positive [EBV(+)] tumors and cell li...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.72.9.7075-7083.1998

    authors: Tao Q,Robertson KD,Manns A,Hildesheim A,Ambinder RF

    更新日期:1998-09-01 00:00:00

  • Resolving the assembly state of herpes simplex virus during axon transport by live-cell imaging.

    abstract::Neurotropic herpesviruses depend on long-distance axon transport for the initial establishment of latency in peripheral ganglia (retrograde transport) and for viral spread in axons to exposed body surfaces following reactivation (anterograde transport). Images of neurons infected with herpes simplex virus type 1 (HSV-...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01296-10

    authors: Antinone SE,Zaichick SV,Smith GA

    更新日期:2010-12-01 00:00:00

  • Contribution of glutamine residues in the helix 4-5 loop to capsid-capsid interactions in simian immunodeficiency virus of macaques.

    abstract:UNLABELLED:Following retrovirus entry, the viral capsid (CA) disassembles into its component capsid proteins. The rate of this uncoating process, which is regulated by CA-CA interactions and by the association of the capsid with host cell factors like cyclophilin A (CypA), can influence the efficiency of reverse transc...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.01388-14

    authors: Tipper C,Sodroski JG

    更新日期:2014-09-01 00:00:00