Abstract:
:Influenza A virus (IAV) remains a global health concern despite the availability of a seasonal vaccine. It is difficult to predict which strains will circulate during influenza season, and therefore, it is extremely challenging to test novel vaccines in the human population. To overcome this obstacle, new vaccines must be tested in challenge studies. This approach poses significant safety problems, since current pharmacological interventions for IAV are poorly efficacious. New methods are needed to enhance the safety of these challenge studies. In this study, we have generated a virus expressing a small-molecule-assisted shutoff (SMASh) tag as a safety switch for IAV replication. The addition of the SMASh tag to an essential IAV protein allows for small-molecule-mediated inhibition of replication. Treatment with this drug controls the replication of a SMASh-tagged virus in vitro and in vivo This model for restriction of viral replication has potential for broad applications in vaccine studies, virotherapy, and basic virus research.IMPORTANCE Influenza A virus (IAV) causes significant morbidity and mortality annually worldwide, despite the availability of new formulations of the vaccine each season. There is a critical need to develop more-efficacious vaccines. However, testing novel vaccines in the human population in controlled studies is difficult due to the limited availability and efficacy of intervention strategies should the vaccine fail. There are also significant safety concerns for work with highly pathogenic IAV strains in the laboratory. Therefore, novel strategies are needed to improve the safety of vaccine studies and of research on highly pathogenic IAV. In this study, we developed an IAV strain engineered to contain a small-molecule-mediated safety switch. This tag, when attached to an essential viral protein, allows for the regulation of IAV replication in vitro and in vivo This strategy provides a platform for the regulation of virus replication without targeting viral proteins directly.
journal_name
J Viroljournal_title
Journal of virologyauthors
Fay EJ,Aron SL,Stone IA,Waring BM,Plemper RK,Langlois RAdoi
10.1128/JVI.01677-18subject
Has Abstractpub_date
2018-12-10 00:00:00issue
1eissn
0022-538Xissn
1098-5514pii
JVI.01677-18journal_volume
93pub_type
杂志文章abstract::Nonglucosylated T6 phage (T6gtam 16am30, hereafter called T6alpha gt-) were found to have two structural anomalies when compared with wild-type T6. The DNA of T6alpha gt- phage contains single-strand interruptions. These can be seen both during infection, in the pool of replicating DNA, and in DNA extracted from purif...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.4.776-784.1975
更新日期:1975-04-01 00:00:00
abstract::We observed two patterns of chemokine expression in the lungs of mice infected with murine gammaherpesvirus 68: peaks of chemokine expression correlated with or occurred after the peak of viral gene expression. Chemokine expression remained elevated through 29 days postinfection. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.20.10518-10523.2002
更新日期:2002-10-01 00:00:00
abstract::The degree of genetic heterogeneity of DNA virus populations in nature and its consequences for disease control are virtually unknown. The parvovirus minute virus of mice (MVMi) was used here to investigate (i) the frequency of antibody-escape mutants in populations of a DNA virus and (ii) the ability of a DNA virus t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.4.2701-2708.2003
更新日期:2003-02-01 00:00:00
abstract::The binding properties of seven CD4-blocking monoclonal antibodies raised against recombinant gp120 of human immunodeficiency virus type 1 strain MN (HIV-1MN) and two CD4-blocking monoclonal antibodies to recombinant envelope glycoproteins gp120 and gp160 of substrain IIIB of HIVLAI were analyzed. With a panel of reco...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.6179-6191.1993
更新日期:1993-10-01 00:00:00
abstract::The protease (PR) from human immunodeficiency virus (HIV) is essential for viral replication: this aspartyl protease, active only as a dimer, is responsible for cleavage of the viral polyprotein precursors (Gag and Gag-Pol), to release the functional mature proteins. In this work, we have studied the structure-functio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.15.8216-8226.2003
更新日期:2003-08-01 00:00:00
abstract::Interactions between host factors and the viral replication complex play important roles in host adaptation and regulation of influenza virus replication. A cellular protein, nuclear factor 90 (NF90), was copurified with H5N1 viral nucleoprotein (NP) from human cells in which NP was transiently expressed and identifie...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00735-09
更新日期:2009-08-01 00:00:00
abstract::The features of herpes simplex virus 1 (HSV-1) strain 129 (H129), including natural neurotropism and anterograde transneuronal trafficking, make it a potential tool for anterograde neural circuitry tracing. Recently anterograde polysynaptic and monosynaptic tracers were developed from H129 and have been applied for th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01957-19
更新日期:2020-03-31 00:00:00
abstract::The development of cancer vaccines requires approaches to induce expansion and functional differentiation of tumor antigen-specific cytotoxic T lymphocyte (CTL) effectors which posses cytolytic capability and produce cytokines. Efficient induction of such cells is hindered by the poor immunogenicity of tumor antigens ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.13.7411-7424.2003
更新日期:2003-07-01 00:00:00
abstract::In some retroviruses, such as Rous sarcoma virus and prototype foamy virus, Gag proteins are known to shuttle between the nucleus and the cytoplasm and are implicated in nuclear export of the viral genomic unspliced RNA (gRNA) for subsequent encapsidation. A similar function has been proposed for human immunodeficienc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06874-11
更新日期:2012-03-01 00:00:00
abstract::We have previously reported that infection with herpes simplex virus type 1 (HSV-1) activates expression of the human immunodeficiency virus type 1 (HIV-1) provirus in T cells. Activation of the HIV-1 provirus correlated with the activation of binding of 55- and 85-kDa proteins to the kappa B enhancer and binding of t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.7.4427-4431.1993
更新日期:1993-07-01 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::A rat nephroma cell line was found to be a carrier culture of the Kilham rat virus. Infectious virus was demonstrable only by passage of culture materials into other host systems. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.4.3.313-314.1969
更新日期:1969-09-01 00:00:00
abstract::Worldwide amphibian population declines have been ascribed to global warming, increasing pollution levels, and other factors directly related to human activities. These factors may additionally be favoring the emergence of novel pathogens. In this report, we have determined the complete genome sequence of the emerging...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.07108-11
更新日期:2012-04-01 00:00:00
abstract::The transforming proteins of the small DNA tumor viruses, simian virus 40 (SV40), adenovirus, and human papillomavirus (HPV) target a number of identical cellular regulators whose functional abrogation is required for transformation. However, while both adenovirus E1A and SV40 large T transforming properties also depe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.8.6209-6219.1999
更新日期:1999-08-01 00:00:00
abstract::5' S-isobutyl-adenosine (SIBA), a structural analogue of S-adenosylhomocysteine, reversibly blocks the multiplication of herpes simplex type 1 virus. In the presence of SIBA, viral protein synthesis is inhibited. After removing SIBA the synthesis of proteins starts rapidly again. The new polypeptides are mainly alpha ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.22.1.160-167.1977
更新日期:1977-04-01 00:00:00
abstract::Passage of native classical swine fever virus (CSFV) in cultured swine kidney cells (SK6 cells) selects virus variants that attach to the surface of cells by interaction with membrane-associated heparan sulfate (HS). A Ser-to-Arg change in the C terminus of envelope glycoprotein E(rns) (amino acid 476 in the open read...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.20.9585-9595.2001
更新日期:2001-10-01 00:00:00
abstract::Several aspects of the terminal stages of T4 head maturation were investigated using ts and am mutants blocked at single steps of the assembly pathway. We had previously found that cells infected with mutants of gene 13, e.g., tsN38 and amE609, accumulated both stable (10 to 20%)- and fragile (80%)-filled head precurs...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.17.2.550-567.1976
更新日期:1976-02-01 00:00:00
abstract::The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells. This inhibition wa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.12.6461-6467.1991
更新日期:1991-12-01 00:00:00
abstract::To replicate its segmented, double-stranded RNA (dsRNA) genome, the rotavirus RNA-dependent RNA polymerase, VP1, must recognize viral plus-strand RNAs (+RNAs) and guide them into the catalytic center. VP1 binds to the conserved 3' end of rotavirus +RNAs via both sequence-dependent and sequence-independent contacts. Se...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01689-10
更新日期:2011-03-01 00:00:00
abstract:UNLABELLED:PML is the organizer of cellular structures termed nuclear domain 10 (ND10) or PML-nuclear bodies (PML-NBs) that act as key mediators of intrinsic immunity against human cytomegalovirus (HCMV) and other viruses. The antiviral function of ND10 is antagonized by viral regulatory proteins such as the immediate ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01973-15
更新日期:2015-11-11 00:00:00
abstract::Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for chikungunya fever. Nonstructural protein 2 (nsP2), a multifunctional protein essential for viral replication, has an N-terminal helicase region (nsP2h), which as both nucleotide triphosphatase and RNA triphosphatase activities, as well as a C-ter...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01470-20
更新日期:2020-12-16 00:00:00
abstract::Structures of somatically acquired murine leukemia virus (MuLV) genomes present in the DNA of a large panel of MuLV-induced C57BL and BALB/c B and non-T/non-B cell lymphomas were compared with those present in MuLV-induced T-cell lymphomas induced in the same low-"spontaneous"-lymphoma-incidence mice. Analyses were pe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.3.1037-1047.1986
更新日期:1986-03-01 00:00:00
abstract::Currently there is limited information about the quality of immune responses elicited by candidate human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)-based immunogens in primates. Here we describe a comprehensive analysis of neutralizing antibody and T-cell responses obtained in cynomolgus macaque...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01102-08
更新日期:2009-01-01 00:00:00
abstract::Chinese hamster ovary (CHO) cells have recently been used for identification of receptors for several alphaherpesviruses, including pseudorabies virus (PrV) (R. J. Geraghty, C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and P. G. Spear, Science 280:1618-1620, 1998). The experiments were based on the fact that CHO cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.10.8019-8026.1999
更新日期:1999-10-01 00:00:00
abstract::The E3 complex transcription unit of adenovirus encodes four major mRNAs (a, c, f, and h) and two minor (d and e) mRNAs with overlapping exons, alternative splice sites, and two polyadenylation sites, termed E3A (upstream) and E3B (downstream). mRNAs a and d use the E3A polyadenylation site, and mRNAs c, e, f, and h u...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.10.5914-5923.1992
更新日期:1992-10-01 00:00:00
abstract::Hepatitis C virus (HCV)-specific CD8 cell exhaustion may represent a mechanism of HCV persistence. The inhibitory receptor PD-1 has been reported to be up-regulated in exhausted CD8 cells. Therefore, we studied PD-1 expression longitudinally during acute HCV infection. Most HCV-specific CD8 cells expressed PD-1 at the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01177-06
更新日期:2006-11-01 00:00:00
abstract::Murine gammaherpesvirus 68 (MHV68 [also known as gammaHV-68]) is distinguished by its ability to replicate to high titers in cultured cells, making it an excellent candidate for studying gammaherpesvirus virion composition. Extracellular MHV68 virions were isolated, and abundant virion-associated proteins were identif...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.24.13425-13432.2003
更新日期:2003-12-01 00:00:00
abstract::Macrophages perform a central role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection and have been implicated as the cell type most prominent in the development of central nervous system impairment. In this study, we evaluated the effect of interaction between macrophages and endothelial cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.4.2133-2139.1995
更新日期:1995-04-01 00:00:00
abstract::Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflamm...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01491-16
更新日期:2016-11-28 00:00:00
abstract::Mutations at amino acids 143, 148, and 155 in HIV-1 integrase (IN) define primary resistance pathways in subjects failing raltegravir (RAL)-containing treatments. Although each pathway appears to be genetically distinct, shifts in the predominant resistant virus population have been reported under continued drug press...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06618-11
更新日期:2012-07-01 00:00:00