Abstract:
:The phenomenon whereby the host immune system responds to only a few of the many possible epitopes in a foreign protein is termed immunodominance. Immunodominance occurs not only during microbial infection but also following vaccination, and clarification of the underlying mechanism may permit the rational design of vaccines which can circumvent immunodominance, thereby inducing responses to all epitopes, dominant and subdominant. Here, we show that immunodominance affects DNA vaccines and that the effects can be avoided by the simple expedient of epitope separation. DNA vaccines encoding isolated dominant and subdominant epitopes induce equivalent responses, confirming a previous demonstration that coexpression of dominant and subdominant epitopes on the same antigen-presenting cell (APC) is central to immunodominance. We conclude that multiepitope DNA vaccines should comprise a cocktail of plasmids, each with its own epitope, to allow maximal epitope dispersal among APCs. In addition, we demonstrate that subdominant responses are actively suppressed by dominant CD8(+) T-cell responses and that gamma interferon (IFN-gamma) is required for this suppression. Furthermore, priming of CD8(+) T cells to a single dominant epitope results in strong suppression of responses to other normally dominant epitopes in immunocompetent mice, in effect rendering these epitopes subdominant; however, responses to these epitopes are increased 6- to 20-fold in mice lacking IFN-gamma. We suggest that, in agreement with our previous observations, IFN-gamma secretion by CD8(+) T cells is highly localized, and we propose that its immunosuppressive effect is focused on the APC with which the dominant CD8(+) T cell is in contact.
journal_name
J Viroljournal_title
Journal of virologyauthors
Rodriguez F,Harkins S,Slifka MK,Whitton JLdoi
10.1128/jvi.76.9.4251-4259.2002subject
Has Abstractpub_date
2002-05-01 00:00:00pages
4251-9issue
9eissn
0022-538Xissn
1098-5514journal_volume
76pub_type
杂志文章abstract::DNA vaccines have recently emerged at the forefront of approaches to harness the immune system in the prevention and treatment of viral infections, as well as the prevention and treatment of cancers. However, these vaccines suffer from limited efficacy since they often fail to produce significant antigen-specific CD8(...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01954-09
更新日期:2010-03-01 00:00:00
abstract::In vitro analysis of the catalytic DNA polymerase encoded by vaccinia virus has demonstrated that it is innately distributive, catalyzing the addition of <10 nucleotides per primer-template binding event in the presence of 8 mM MgCl(2) or 40 mM NaCl (W. F. McDonald and P. Traktman, J. Biol. Chem. 269:31190-31197, 1994...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.24.12298-12307.2001
更新日期:2001-12-01 00:00:00
abstract::Paramyxoviruses such as human parainfluenza viruses that bear inserts encoding protective antigens of heterologous viruses can induce an effective immunity against the heterologous viruses in experimental animals. However, vectors based on common human pathogens would be expected to be restricted in replication in the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.21.13275-13284.2005
更新日期:2005-11-01 00:00:00
abstract::Molluscs, comprising one of the most successful phyla, lack clear evidence of adaptive immunity and yet thrive in the oceans, which are rich in viruses. There are thought to be nearly 120,000 species of Mollusca, most living in marine habitats. Despite the extraordinary abundance of viruses in oceans, molluscs often h...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.00287-15
更新日期:2015-08-01 00:00:00
abstract::Recombinant human cytomegaloviruses that do not express UL97 kinase activity exhibit a distinctive plaque morphology characterized by the formation of highly refractile bodies late in infection. These structures were also observed in infected cells treated with the UL97 kinase inhibitor maribavir. Nuclear inclusions w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.24.15494-15502.2005
更新日期:2005-12-01 00:00:00
abstract::Functions of viral proteins can be regulated through phosphorylation by serine/threonine kinases in plants, but little is known about the involvement of tyrosine kinases in plant virus infection. In this study, TGBp3, one of the three movement proteins encoded by a triple gene block (TGB) of Potato mop-top virus (PMTV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03388-12
更新日期:2013-04-01 00:00:00
abstract::To examine the cell fusion activity of hepatitis C virus (HCV) envelope proteins (E1 and E2), we have established a sensitive cell fusion assay based on the activation of a reporter gene as described previously (O. Nussbaum, C. C. Broder, and E. A. Berger, J. Virol. 68:5411-5422, 1994). The chimeric HCV E1 and E2 prot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.11.5066-5074.2000
更新日期:2000-06-01 00:00:00
abstract::Picornavirus-infected cells contain a double-stranded RNA (replicative form [RF] RNA), composed of viral genomic RNA hydrogen bonded to cRNA of similar nucleotide length. Mengovirus RF RNA reacted with a succinimide ester of biotin was shown by electron microscopy to bind avidin-coupled polymethacrylate spheres. These...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.1.229-237.1981
更新日期:1981-07-01 00:00:00
abstract::In 2002, severe acute respiratory syndrome (SARS)-coronavirus (CoV) appeared as a novel human virus with high similarity to bat coronaviruses. However, while SARS-CoV uses the human angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry, no coronavirus isolated from bats appears to use ACE2. Here we show t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00311-12
更新日期:2012-06-01 00:00:00
abstract::The major immediate-early (MIE) gene of human cytomegalovirus (HCMV) produces multiple mRNAs through differential splicing and polyadenylation. Reverse transcriptase PCR was used to characterize transcripts from exons 1, 2, 3, and 4 (immediate-early 1 [IE1]). The expected IE72 and IE19 mRNAs were detected, as well as ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.15.8191-8200.2004
更新日期:2004-08-01 00:00:00
abstract::Cellular inhibitor of apoptosis protein 2 (cIAP2) is a potent suppressor of apoptotic cell death. We have shown previously that cIAP2 is involved in the tumor necrosis factor alpha (TNF-α)-induced anti-hepatitis B virus (HBV) response; however, the mechanism for this antiviral effect remains unclear. In the present st...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00879-11
更新日期:2011-11-01 00:00:00
abstract::Herpesvirus nucleocapsids traverse the nuclear envelope into the cytoplasm in a process called nuclear egress that includes disruption of the nuclear lamina. In several herpesviruses, a key player in nuclear egress is a complex of two proteins, whose homologs in human cytomegalovirus (HCMV) are UL50 and UL53. However,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02358-13
更新日期:2014-01-01 00:00:00
abstract::Normal levels of the hypermodified pyrimidine, alpha-putrescinylthymine, which is formed from hydhydroxymethyluracil at the polynucleotide level (Maltman et al., J. Virol. 34:354-359, 1984), are not required in bacteriophage luminal diameterW-14 DNA for the DNA to serve as a replicative template in luminal diameterW-1...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.52.3.1036-1038.1984
更新日期:1984-12-01 00:00:00
abstract::The nucleotide sequences of the termini of the mature pseudorabies virus genome and of the junction between these termini in concatemeric DNA were compared. To ensure conservation of unmodified 5' and 3' termini, the end fragments obtained directly (uncloned) from mature viral DNA were sequenced. The sequence obtained...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.3.1183-1185.1986
更新日期:1986-12-01 00:00:00
abstract::We have previously shown that styrylquinolines (SQLs) are integrase inhibitors in vitro. They compete with the long terminal repeat substrate for integrase. Here, we describe the cellular mode of action of these molecules. We show that SQLs do not interfere with virus entry. In fact, concentrations of up to 20 times t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.11.5728-5736.2004
更新日期:2004-06-01 00:00:00
abstract::Previous studies have suggested that the U(L)17 gene of herpes simplex virus type 1 (HSV-1) is essential for virus replication. In this study, viral mutants incorporating either a lacZ expression cassette in place of 1,490 bp of the 2,109-bp U(L)17 open reading frame [HSV-1(deltaU(L)17)] or a DNA oligomer containing a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.5.3779-3788.1998
更新日期:1998-05-01 00:00:00
abstract::Latency is an integral feature of the pathogenesis of cytomegalovirus infection and disease. Using in situ hybridization, we detected viral DNA in the splenic stroma of mice with acute murine cytomegalovirus (MCMV) infection but could not detect latent infection. By using enzymatic amplification of a 700-bp region of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.6.3330-3334.1991
更新日期:1991-06-01 00:00:00
abstract::The complete genomic sequence of kelp fly virus (KFV), originally isolated from the kelp fly, Chaetocoelopa sydneyensis, has been determined. Analyses of its genomic and structural organization and phylogeny show that it belongs to a hitherto undescribed group within the picorna-like virus superfamily. The single-stra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.21.13385-13398.2005
更新日期:2005-11-01 00:00:00
abstract::We measured the quantity of plasma feline immunodeficiency virus (FIV) RNA using a real-time sequence detecting system. Plasma viral RNA load was shown to correlate with the clinical stage, survival time, and disease progression in naturally FIV-infected cats. The present study indicates that the plasma viral RNA load...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.19.10079-10083.2002
更新日期:2002-10-01 00:00:00
abstract::Transduction of the liver with single-stranded adeno-associated virus serotype 2 (AAV2) vectors is inefficient; less than 10% of hepatocytes are permissive for stable transduction, and transgene expression is characterized by a lag phase of up to 6 weeks. AAV2-based vector genomes packaged inside AAV6 or AAV8 capsids ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.6.3110-3122.2004
更新日期:2004-03-01 00:00:00
abstract::Antibodies present in two peritoneal exudates of rats bearing abdominal tumors induced by UR2-transformed rat cells were characterized. The ability to immunoprecipitate p68gag-ros and to inhibit the protein and phospholipid kinase activities of this protein was investigated. One of the exudates specifically inhibited ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.765-767.1986
更新日期:1986-11-01 00:00:00
abstract::Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRp) that acts as a key player in the HCV replication complex. Understanding the interplay between the viral and cellular components of the HCV replication complex could provide new insight for prevention of the progression of...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02526-12
更新日期:2013-05-01 00:00:00
abstract::The large (L) protein of Ebola virus is a key protein for virus replication. Its N-terminal region harbors the RNA-dependent RNA polymerase activity, and its C terminus contains a cap assembling line composed of a capping domain and a methyltransferase domain (MTase) followed by a C-terminal domain (CTD) of unknown fu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00520-20
更新日期:2020-06-01 00:00:00
abstract::Cells expressing the low pH-triggered class II viral fusion protein E1 of Semliki Forest virus (SFV) were fused to target cells. Fusion was monitored by electrical capacitance and aqueous dye measurements. Electrical voltage-clamp measurements showed that SFV E1-induced cell-cell fusion occurred quickly after acidific...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01256-07
更新日期:2007-10-01 00:00:00
abstract::Treatment with sodium dodecyl sulfate (SDS) converted the vaccinia virus strain IHD-J into particles of two types: (i) ghosts which possessed a thin-membrane vesicle derived from basement part of the virus membrane with attached lateral bodies and a membranous structure derived from the core wall and (ii) aggregates o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.929-938.1984
更新日期:1984-06-01 00:00:00
abstract::HTG2 hamster cells produce a defective murine sarcoma virus lacking gp70 and, consequently, viral surface projections (knobs), but the lack of knobs appears to have no effect on intramembrane particle distribution. In addition, it has been noted that the core of the virus remains in the "immature" form as a result of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.3.872-877.1980
更新日期:1980-12-01 00:00:00
abstract::Retroviral DNA integration requires the activity of at least one viral protein, the integrase (IN) protein. We cloned and expressed the integrase gene of feline immunodeficiency virus (FIV) in Escherichia coli as a fusion to the malE gene and purified the IN fusion protein by affinity chromatography. The protein is ac...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.3.1468-1474.1994
更新日期:1994-03-01 00:00:00
abstract::Open reading frame (ORF) E4 is a 353-base-pair ORF of bovine papillomavirus type 1. To determine the biological activities of this ORF in mouse C127 cells, we analyzed the effects of two constructed mutations which are predicted to prevent synthesis of ORF E4 proteins while leaving the amino acid sequence encoded by t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.4.1248-1252.1987
更新日期:1987-04-01 00:00:00
abstract::The ability of the gamma(1)34.5 protein to suppress the PKR response plays a crucial role in herpes simplex virus pathogenesis. In this process, the gamma(1)34.5 protein associates with protein phosphatase 1 to form a large complex that dephosphorylates eIF-2alpha and thereby prevents translation shutoff mediated by P...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.14.7653-7666.2004
更新日期:2004-07-01 00:00:00
abstract::We have constructed two point mutants of Rous sarcoma virus in which the amino-terminal glycine residue of the transforming protein, p60src, was changed to an alanine or a glutamic acid residue. Both mutant proteins failed to become myristylated and, more importantly, no longer transformed cells. The lack of transform...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.2.468-474.1986
更新日期:1986-05-01 00:00:00