Abstract:
:The development of immunization strategies to protect against ocular infection with herpes simplex virus 1 (HSV-1) must address the issue of the effects of the strategy on the establishment of latency in the trigeminal ganglia (TG). It is the reactivation of this latent virus that can cause recurrent disease and corneal scarring. CD8(+) T cells and dendritic cells (DCs) have been implicated in the establishment and maintenance of latency through several lines of inquiry. The objective of the current study was to use CD8α(-/-) and CD8β(-/-) mice to further evaluate the contributions of CD8(+) T cells and the CD8α(+) and CD8α(-) subpopulations of DCs to the protection afforded against ocular infection by immunization against HSV-1 and their potential to increase latency. Neutralizing antibody titers were similar in immunized CD8α(-/-), CD8β(-/-), and wild-type (WT) mice, as was virus replication in the eye. However, on day 3 postinfection (p.i.), the copy number of HSV-1 glycoprotein B (gB) was higher in the corneas and TG of CD8α(-/-) mice than those of WT mice, whereas on day 5 p.i. it was lower. As would be anticipated, the lack of CD8α(+) or CD8β(+) cells affected the levels of type I and type II interferon transcripts, but the effects were markedly time dependent and tissue specific. The levels of latent virus in the TG, as estimated by measurement of LAT transcripts and in vitro explant reactivation assays, were lower in the immunized, ocularly challenged CD8α(-/-) and WT mice than in their CD8β(-/-) counterparts. Immunization reduced the expression of PD-1, a marker of T-cell exhaustion, in the TG of ocularly challenged mice, and mock-immunized CD8α(-/-) mice had lower levels of PD-1 expression and latency than mock-immunized WT or CD8β(-/-) mice. The expansion of the CD8α(-) subpopulation of DCs through injection of WT mice with granulocyte-macrophage colony-stimulating factor (GM-CSF) DNA reduced the amount of latency and PD-1 expression in the TG of infected mice. In contrast, injection of FMS-like tyrosine kinase 3 ligand (Flt3L) DNA, which expanded both subpopulations, was less effective. Our results suggest that the absence of both CD8α(+) T cells and CD8α(+) DCs does not reduce vaccine efficacy, either directly or indirectly, in challenged mice and that administration of GM-CSF appears to play a beneficial role in reducing latency and T-cell exhaustion. Importance: In the past 2 decades, two large clinical HSV vaccine trials were performed, but both vaccine studies failed to reach their goals. Thus, as an alternative to conventional vaccine studies, we have used a different strategy to manipulate the host immune responses in an effort to induce greater protection against HSV infection. In lieu of the pleiotropic effect of CD8α(+) DCs in HSV-1 latency, in this report, we show that the absence of CD8α(+) T cells and CD8α(+) DCs has no adverse effect on vaccine efficacy. In line with our hypothesis, we found that pushing DC subpopulations from CD8α(+) DCs toward CD8α(-) DCs by injection of GM-CSF reduced the amount of latent virus and T-cell exhaustion in TG. While these studies point to the lack of a role for CD8α(+) T cells in vaccine efficacy, they in turn point to a role for GM-CSF in reducing HSV-1 latency.
journal_name
J Viroljournal_title
Journal of virologyauthors
Matundan H,Mott KR,Ghiasi Hdoi
10.1128/JVI.00913-14subject
Has Abstractpub_date
2014-07-01 00:00:00pages
8016-27issue
14eissn
0022-538Xissn
1098-5514pii
JVI.00913-14journal_volume
88pub_type
杂志文章abstract::We used the mammalian reoviruses to determine the molecular basis of the clearance of a virus from the bloodstream by specific organs. Reovirus serotypes 1 (T1) and 3 (T3) were radiolabeled with [35S]methionine or 125I, and the viruses were injected intravenously into weanling rats. The distribution of radioactivity w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.2.545-551.1988
更新日期:1988-02-01 00:00:00
abstract::Immunoglobulin G1 (IgG1), IgG2a, and IgG2b switch variants were derived from an IgG3 monoclonal antibody directed against the VP3 envelope glycoprotein of lactate dehydrogenase-elevating virus (LDV). Among the four antibodies, IgG2a delayed the onset and progression of LDV-induced polioencephalomyelitis more than did ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.1.432-435.2002
更新日期:2002-01-01 00:00:00
abstract::Rigid amphipathic fusion inhibitors (RAFIs) are lipophilic inverted-cone-shaped molecules thought to antagonize the membrane curvature transitions that occur during virus-cell fusion and are broad-spectrum antivirals against enveloped viruses (Broad-SAVE). Here, we show that RAFIs act like membrane-binding photosensit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02907-13
更新日期:2014-02-01 00:00:00
abstract::During latent herpes simplex virus type 1 (HSV-1) infection in the trigeminal ganglia of mice, three virus-specific transcripts, 2.0, 1.5, and 1.45 kilobases (kb), are detectable by Northern (RNA) blot analysis, but only the 2.0-kb transcript can be detected in HSV-1-infected tissue culture cells (J.G. Spivack and N. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3281-3287.1988
更新日期:1988-09-01 00:00:00
abstract::Infection with the murine coronavirus strain JHM decreases cell surface expression of major histocompatibility complex class I antigens. Northern blots showed that JHM virus infection rapidly reduced the level of actin mRNA, whereas the levels of major histocompatibility complex class I and tubulin mRNAs were reduced ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.10.6815-6819.1994
更新日期:1994-10-01 00:00:00
abstract::Recombinant vaccinia viruses that express defective retroviral vectors upon a single infection event in normal host cells were constructed. The gag-pol and envelope genes and a retroviral vector unit were inserted as vaccinia virus promoter-controlled transcription units at three separate loci. The triple recombinant ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.12.7017-7025.2003
更新日期:2003-06-01 00:00:00
abstract::The RNA polymerase in the nucleocapsid of Pseudomonas phaseolicola bacteriophage phi 6 transcribed large, medium, and small single-stranded RNA from the viral double-stranded RNA genome by a semiconservative (displacement) mechanism. Approximately 23%, 63%, and 65% of the nucleocapsid particles in the assay mixture sy...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.33.2.769-773.1980
更新日期:1980-02-01 00:00:00
abstract::We have studied the fate of CD4 in CEM T cells expressing a human immunodeficiency virus type 1 HIV-1 Nef protein. Nef triggered a rapid endocytosis and a degradation of CD4, while most of the p56lck was upheld at the cell membrane. In the presence of Nef, CD4 accumulated in acidic intracellular vesicles that were not...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.1.528-533.1995
更新日期:1995-01-01 00:00:00
abstract::Primary telencephalic cultures derived from neonatal Wistar Furth rats were able to support the growth of coronavirus JHM if a viable neuronal population was maintained. This occurred under serum-free defined, but not serum-supplemented, growth conditions. The importance of neurons in establishing infections in mixed ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.9.5013-5028.1991
更新日期:1991-09-01 00:00:00
abstract::Resistance or susceptibility of various mouse strains to central nervous system disease caused by different strains of coronavirus is well known. Data from the present study draw attention to an additional, genetically determined mechanism controlling CV infections. The resistance to A59 and JHM virus (JHMV) associate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3371-3377.1988
更新日期:1988-09-01 00:00:00
abstract::Here we report the complete genome sequence of a dengue virus serotype 2 (DENV-2) strain, GZ40, isolated in Guangdong, China, in 2010. A phylogenetic analysis classified GZ40 into the Cosmopolitan genotype, while previous Chinese DENV-2 isolates belong to the Asian I genotype. The reemergence of the Cosmopolitan genot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02562-12
更新日期:2012-12-01 00:00:00
abstract::Despite the long-standing observation that herpes simplex virus (HSV) latency-associated transcript (LAT) promoter deletion viruses show impaired recurrence phenotypes in relevant animal models, the mechanism by which these sequences exert this phenotypic effect is unknown. We constructed and evaluated four mutant HSV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00642-18
更新日期:2018-06-29 00:00:00
abstract::Two virus-specific species of newly synthesized DNA were isolated from rat fibroblast cell cultures infected with the Kilham rat virus (RV). These two DNA species were purified; their behavior on hydroxyapatite chromatography and their sedimentation coefficients in sucrose gradients were determined. One of the two spe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.20.1.86-95.1976
更新日期:1976-10-01 00:00:00
abstract::The U(S)3 open reading frame of herpes simplex virus 1 (HSV-1) was reported to encode two mRNAs each directing the synthesis of the same protein. We report that the U(S)3 gene encodes two proteins. The predominant U(S)3 protein is made in wild-type HSV-1-infected cells. The truncated mRNA and a truncated protein desig...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.13.8470-8479.2005
更新日期:2005-07-01 00:00:00
abstract::The susceptibility of monocyte-derived cultured dendritic cells (DCs) to human immunodeficiency virus (HIV) infection and their role in viral transmission in the immune response were studied in detail. We observed that highly purified cultured DCs were infected with the T-tropic Lai strain of HIV type 1 (HIV-1Lai) via...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.7.4544-4547.1995
更新日期:1995-07-01 00:00:00
abstract::The size of the product RNA synthesized by the poliovirus RNA polymerase and host factor was significantly affected by the type of column chromatography used to purify the polymerase. Dimer length product RNA was synthesized by the polymerase purified by chromatography on hydroxylapatite. This contrasted with the mono...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.2.611-614.1987
更新日期:1987-02-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) normally assembles into particles of 100 to 120 nm in diameter by budding through the plasma membrane of the cell. The Gag polyprotein is the only viral protein that is required for the formation of these particles. We have used an in vitro assembly system to examine the ass...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.3.2270-2279.1999
更新日期:1999-03-01 00:00:00
abstract::Influenza A H9N2 viruses are common poultry pathogens that occasionally infect swine and humans. It has been shown previously with H9N2 viruses that reassortment can generate novel viruses with increased transmissibility. Here, we demonstrate the modeling power of a novel transfection-based inoculation system to selec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02677-13
更新日期:2014-01-01 00:00:00
abstract::In our search for novel inhibitors of herpes simplex virus type 1 (HSV-1), a new class of thiourea inhibitors was discovered. N-(4-[3-(5-Chloro-2,4-dimethoxyphenyl)-thioureido]-phenyl)-acetamide and its 2-fluoro-benzamide derivative inhibited HSV-1 replication. HSV-2, human cytomegalovirus, and varicella-zoster virus ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.19.9054-9061.2000
更新日期:2000-10-01 00:00:00
abstract::Human cytomegalovirus (HCMV) infection of monocyte-derived macrophages (MDM) results in delayed and nonlytic productive viral growth. During late stages of replication, infectious virus remains cell associated in cytoplasmic vacuoles. In order to understand HCMV survival and persistence in MDM, we examined mechanisms ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.1855-1862.1996
更新日期:1996-03-01 00:00:00
abstract::The retrovirus type B leukemogenic virus (TBLV) causes T-cell lymphomas in mice. We have identified the Rorgamma locus as an integration site in 19% of TBLV-induced tumors. Overexpression of one or more Rorgamma isoforms in >77% of the tumors tested may complement apoptotic effects of c-myc overexpression. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.9.4943-4946.2004
更新日期:2004-05-01 00:00:00
abstract::A fresh inoculum of human adenovirus type 12 (Ad12) was obtained from the American Type Culture Collection and passaged once on human embryonic kidney cells, and Ad12 DNA was prepared from the first-passage yield to avoid higher passages which might have generated host-virus DNA recombinants. The 18 PstI fragments of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.1.379-389.1994
更新日期:1994-01-01 00:00:00
abstract::A host-mediated RNA-editing event allows hepatitis delta virus (HDV) to express two essential proteins, the small delta antigen (HDAg-S) and the large delta antigen (HDAg-L), from a single open reading frame. One or several members of the ADAR (adenosine deaminases that act on RNA) family are thought to convert the ad...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.18.8547-8555.2001
更新日期:2001-09-01 00:00:00
abstract::We are using site-directed mutagenesis of single viral genes to identify and analyze the genetic determinants of human and simian immunodeficiency virus pathogenicity. In a first approach, we have constructed a series of simian immunodeficiency virus SIVmac nef mutants by partial deletion and insertions in the nef gen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.10.5237-5243.1991
更新日期:1991-10-01 00:00:00
abstract::Relatively little is known at the functional genomic level about the global host response to human immunodeficiency virus type 1 (HIV-1) infection. Microarray analyses by several laboratories, including our own, have revealed that HIV-1 infection causes significant changes in host mRNA abundance and regulation of seve...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00288-07
更新日期:2007-07-01 00:00:00
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
更新日期:2007-02-01 00:00:00
abstract::The combination of an amino acid deletion at codon 67 (delta 67) and Thr-to-Gly change at codon 69 (T69G) in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is associated with high-level resistance to multiple RT inhibitors. To determine the relative contributions of the delta 67 and T69G...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.23.10958-10964.2000
更新日期:2000-12-01 00:00:00
abstract::Glycoprotein gIII of pseudorabies virus is a major antigen found in the envelopes of virus particles as well as in and on the surfaces of infected cells. It is not an essential gene product for virus growth in tissue culture. In this report, we provide evidence that, although it is not essential, the gIII protein is r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.7.2512-2515.1988
更新日期:1988-07-01 00:00:00
abstract::Epstein-Barr virus (EBV) undergoes latent and lytic replication cycles, and its reactivation from latency to lytic replication is initiated by expression of the two viral immediate-early transactivators, Zta and Rta. In vitro, reactivation of EBV can be induced by anti-immunoglobulin, tetradecanoyl phorbol acetate, an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01602-10
更新日期:2011-03-01 00:00:00
abstract::Numerous RNA viruses generate subgenomic mRNAs (sgRNAs) for expression of their 3'-proximal genes. A major step in control of viral gene expression is the regulation of sgRNA synthesis by specific promoter elements. We used barley yellow dwarf virus (BYDV) as a model system to study transcriptional control in a virus ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.13.5988-5996.2000
更新日期:2000-07-01 00:00:00