Abstract:
:Our previous studies have shown that targeting DNA vaccine-encoded major histocompatibility complex class I epitopes to the proteasome enhanced CD8(+) T-cell induction and protection against lymphocytic choriomeningitis virus (LCMV) challenge. Here, we expand these studies to evaluate CD4(+) T-cell responses induced by DNA immunization and describe a system for targeting proteins and minigenes to lysosomes. Full-length proteins can be targeted to the lysosomal compartment by covalent attachment to the 20-amino-acid C-terminal tail of lysosomal integral membrane protein-II (LIMP-II). Using minigenes encoding defined T-helper epitopes from lymphocytic choriomeningitis virus, we show that the CD4(+) T-cell response induced by the NP(309-328) epitope of LCMV was greatly enhanced by addition of the LIMP-II tail. However, the immunological consequence of lysosomal targeting is not invariably positive; the CD4(+) T-cell response induced by the GP(61-80) epitope was almost abolished when attached to the LIMP-II tail. We identify the mechanism which underlies this marked difference in outcome. The GP(61-80) epitope is highly susceptible to cleavage by cathepsin D, an aspartic endopeptidase found almost exclusively in lysosomes. We show, using mass spectrometry, that the GP(61-80) peptide is cleaved between residues F(74) and K(75) and that this destroys its ability to stimulate virus-specific CD4(+) T cells. Thus, the immunological result of lysosomal targeting varies, depending upon the primary sequence of the encoded antigen. We analyze the effects of CD4(+) T-cell priming on the virus-specific antibody and CD8(+) T-cell responses which are mounted after virus infection and show that neither response appears to be accelerated or enhanced. Finally, we evaluate the protective benefits of CD4(+) T-cell vaccination in the LCMV model system; in contrast to DNA vaccine-induced CD8(+) T cells, which can confer solid protection against LCMV challenge, DNA vaccine-mediated priming of CD4(+) T cells does not appear to enhance the vaccinee's ability to combat viral challenge.
journal_name
J Viroljournal_title
Journal of virologyauthors
Rodriguez F,Harkins S,Redwine JM,de Pereda JM,Whitton JLdoi
10.1128/JVI.75.21.10421-10430.2001subject
Has Abstractpub_date
2001-11-01 00:00:00pages
10421-30issue
21eissn
0022-538Xissn
1098-5514journal_volume
75pub_type
杂志文章abstract:UNLABELLED:The DNA damage response (DDR) that evolved to repair host cell DNA damage also recognizes viral DNA entering the nucleus during infections. Here, we investigated the modulation of DDR signaling during de novo infection of primary endothelial cells by Kaposi's sarcoma-associated herpesvirus (KSHV). Phosphoryl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03126-13
更新日期:2014-03-01 00:00:00
abstract::PM2 DNA was prepared with different superhelical densities (sigma) in order to examine the relationship betweenn supercoiling and the occurrence of a region(s) of unpaired bases in this DNA. A previous study showed that CH3HgOH reacts with native superhelical PM2 DNA more rapidly than the nicked form II. This evaluati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.1.195-204.1976
更新日期:1976-04-01 00:00:00
abstract::We investigated the cis-acting sequences involved in termination of vesicular stomatis virus mRNA synthesis by using bicistronic genomic analogs. All of the cis-acting signals necessary for termination reside within the first 13 nucleotides of the 23-nucleotide conserved gene junction. This 13-nucleotide termination s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8718-8725.1997
更新日期:1997-11-01 00:00:00
abstract::The simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded oncoprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) response. Three immunodominant H-2(b)-restricted epitopes, designated epitopes I, II/III, and IV, have been defined. We investigated whether induction of CTLs directed agains...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.7.5981-5993.1999
更新日期:1999-07-01 00:00:00
abstract::Hepatitis E virus (HEV) replication is not well understood, mainly because the virus does not infect cultured cells efficiently. However, Huh-7 cells transfected with full-length genomes produce open reading frame 2 protein, indicative of genome replication (6). To investigate the role of 3'-terminal sequences in RNA ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.2.1017-1026.2005
更新日期:2005-01-01 00:00:00
abstract::The C-terminal half of the replicase ORF1a polyprotein of the arterivirus equine arteritis virus is processed by a chymotrypsinlike serine protease (SP) (E. J. Snijder et al., J. Biol. Chem. 271:4864-4871, 1996) located in nonstructural protein 4 (nsp4). Three probable SP cleavage sites had previously been identified ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.12.9313-9322.1997
更新日期:1997-12-01 00:00:00
abstract:UNLABELLED:In order to investigate the novel function(s) of the herpes simplex virus 1 (HSV-1) immediate early protein ICP22, we screened for ICP22-binding proteins in HSV-1-infected cells. Our results were as follows. (i) Tandem affinity purification of ICP22 from infected cells, coupled with mass spectrometry-based p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01057-14
更新日期:2014-07-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) particles typically contain small amounts of the surface envelope protein (SU), and this is widely believed to be due to shedding of SU from mature virions. We purified proteins from HIV-1 and SIV isolates using procedures which allow ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.11.5315-5325.2002
更新日期:2002-06-01 00:00:00
abstract::Lymphomas induced by the Abelson murine leukemia virus (A-MuLV) were examined for the expression of biochemical and biological markers associated with A-MuLV transformation before and after in vivo growth in genetically distinguishable host mice. Although all tumors and clonal lines derived from them initially express...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.1.92-103.1982
更新日期:1982-07-01 00:00:00
abstract::Here, we report that specific manipulations of the cellular response to virus infection can cause prevention of apoptosis and consequent establishment of persistent infection. Infection of several human cell lines with Sendai virus (SeV) or human parainfluenza virus 3, two prototypic paramyxoviruses, caused slow apopt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02536-07
更新日期:2008-04-01 00:00:00
abstract::Transient transfection assays indicated that A2L is one of three vaccinia virus intermediate genes that are required for the transcriptional transactivation of viral late genes. We have expressed the A2L open reading frame in Escherichia coli and shown by blotting experiments that the 26-kDa protein binds zinc, a prop...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.5749-5753.1993
更新日期:1993-10-01 00:00:00
abstract::The mitogen-activated protein (MAP) kinase signal transduction pathway is an intracellular signaling cascade which mediates cellular responses to growth and differentiation factors. The MAP kinase pathway can be activated by a wide range of stimuli dependent on the cell types, and this is normally a transient response...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.8051-8056.1995
更新日期:1995-12-01 00:00:00
abstract::Drug susceptibility and mutations in the reverse transcriptase (RT) gene were analyzed with 167 virus isolates from 38 patients treated with nevirapine, a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) RT. Resistant isolates emerged quickly and uniformly in all patients administered nevi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.3.1660-1666.1994
更新日期:1994-03-01 00:00:00
abstract::As a subunit of both the P-L polymerase complex and the P-N assembly complex, the vesicular stomatitis virus (VSV) P protein plays a pivotal role in transcription and replication of the viral genome. Constitutive phosphorylation of this protein is currently thought to be essential for formation of the P-L complex. We ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.7.4538-4548.1996
更新日期:1996-07-01 00:00:00
abstract::The relationship between the vaccinia virus hemagglutinin and hemadsorption was examined. Hemagglutinin synthesis was temporally related to the appearance of the hemadsorption reaction. Only chicken erythrocytes, which reacted with hemagglutinin, hemadsorbed to infected cells, and both of these reactions were inhibite...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.2.290-296.1972
更新日期:1972-02-01 00:00:00
abstract::Varicella-zoster virus (VZV) is the causative agent of chickenpox and herpes zoster (shingles). After the primary infection, the virus remains latent in sensory ganglia and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00128-12
更新日期:2012-08-01 00:00:00
abstract::When herpes simplex virus was inoculated into the flank of a BALB/c mouse by scarification, the local replication of virus was followed by the establishment of an acute ganglionic infection. The subsequent centrifugal spread of this virus along nerves to the skin of the whole dermatome led to the development of a band...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.3.944-948.1985
更新日期:1985-03-01 00:00:00
abstract::Rift Valley fever virus strain MP-12 was generated by serial plaque passages of parental strain ZH548 12 times in MRC-5 cells in the presence of a chemical mutagen, 5-fluorouracil. As a result, MP-12 encoded 4, 9, and 10 mutations in the S, M, and L segments, respectively. Among them, mutations in the M and L segments...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02081-12
更新日期:2012-12-01 00:00:00
abstract::The multifunctional simian and human immunodeficiency virus (SIV and HIV) Nef proteins are important for virulence. We studied the importance of selected Nef functions using an SIV Nef with mutations in two regions that are required for CD4 downregulation. This Nef mutant is defective for downregulating CD4 and, in ad...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.21.9836-9844.2000
更新日期:2000-11-01 00:00:00
abstract::Of the numerous endogenous retroviral elements that are present in the human genome, the abundant HERV-K family is distinct because several members are transcriptionally active and coding for biologically active proteins. A detailed phylogeny of the HERV-K family based on the partial sequence of the reverse transcript...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.3.2365-2375.1999
更新日期:1999-03-01 00:00:00
abstract::The herpes simplex virus type 1 latency-associated transcript (LAT) inhibits apoptosis. We demonstrate here that LAT influences the accumulation of the Bcl-x(L) transcript versus the Bcl-x(S) transcript in Neuro-2A cells. Bcl-x(L) encodes an antiapoptotic protein, whereas Bcl-x(S) encodes a proapoptotic protein. Promo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.19.10714-10718.2003
更新日期:2003-10-01 00:00:00
abstract::Virus was isolated from the lumen of the calyx region of ovaries in the parasitoid wasp Campoletis sonorensis (Hymenoptera: Ichneumonidae), and the nature of the viral DNA was analyzed. DNA purified from a homogeneous band of virus contained double-stranded superhelical molecules which were polydisperse in molecular w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.3.859-870.1982
更新日期:1982-09-01 00:00:00
abstract::Nipah virus (NiV), of the family Paramyxoviridae, was isolated in 1999 in Malaysia from a human fatality in an outbreak of severe human encephalitis, when human infections were linked to transmission of the virus from pigs. Consequently, a swine vaccine able to abolish virus shedding is of veterinary and human health ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00263-06
更新日期:2006-08-01 00:00:00
abstract::Escherichia coli RNA polymerase has been shown to bind to a limited number of Hind and Hae III restriction enzyme fragments. On S13 replicative form DNA there are three major binding sites, and the locations correlate with promoter sites at the beginning of genes a and B and a site overlapping gene D and the beginning...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.27.3.677-687.1978
更新日期:1978-09-01 00:00:00
abstract::The protein (p59rel) encoded by the transforming gene of reticuloendotheliosis virus strain T (REV-T) has been identified in REV-T-transformed avian lymphoid cells by using antisera raised against synthetic peptides whose sequences were derived from three nonoverlapping regions of v-rel (N. R. Rice, T. D. Copeland, S....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.59.1.120-126.1986
更新日期:1986-07-01 00:00:00
abstract::Human herpesvirus 8 (HHV-8) (also known as Kaposi's sarcoma-associated herpesvirus) encodes a novel noncoding polyadenylated nuclear (PAN) RNA (also known as T1.1 or nut-1) during the early phase of lytic replication. PAN RNA is the most abundant transcript of HHV-8, comprising 80% of total poly(A)-selected transcript...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.7.3129-3140.2001
更新日期:2001-04-01 00:00:00
abstract::Foot-and-mouth disease virus (FMDV), a member of the Picornaviridae, is a pathogen of cloven-hoofed animals and causes a disease of major economic importance. Picornavirus-infected cells show changes in cell morphology and rearrangement of cytoplasmic membranes, which are a consequence of virus replication. We show he...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00907-08
更新日期:2008-11-01 00:00:00
abstract::The Epstein-Barr virus (EBV)-determined nuclear antigens EBNA 1, 2, 3, 4, and 6, regularly expressed in EBV-transformed lymphoblastoid cell lines, vary in size among viral strains. We have used this characteristic to trace the spread of the virus within seven families by using an approach called Ebnotyping. Among 33 e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.10.4703-4708.1990
更新日期:1990-10-01 00:00:00
abstract::Vesicular stomatitis virus Indiana strain G protein (VSVind.G) is the most commonly used envelope glycoprotein to pseudotype lentiviral vectors (LV) for experimental and clinical applications. Recently, G proteins derived from other vesiculoviruses (VesG), for example, Cocal virus, have been proposed as alternative LV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00900-18
更新日期:2018-11-12 00:00:00
abstract::Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01753-20
更新日期:2021-01-13 00:00:00