Abstract:
UNLABELLED:The role of NF-κB in influenza A virus (IAV) infection does not reveal a coherent picture, as pro- and also antiviral functions of this transcription factor have been described. To address this issue, we used clustered regularly interspaced short palindromic repeat with Cas9 (CRISPR-Cas9)-mediated genome engineering to generate murine MLE-15 cells lacking two essential components of the NF-κB pathway. Cells devoid of either the central NF-κB essential modulator (NEMO) scaffold protein and thus defective in IκB kinase (IKK) activation or cells not expressing the NF-κB DNA-binding and transactivation subunit p65 were tested for propagation of the SC35 virus, which has an avian host range, and its mouse-adapted variant, SC35M. While NF-κB was not relevant for replication of SC35M, the absence of NF-κB activity increased replication of the nonadapted SC35 virus. This antiviral effect of NF-κB was most prominent upon infection of cells with low virus titers as they usually occur during the initiation phase of IAV infection. The defect in NF-κB signaling resulted in diminished IAV-triggered phosphorylation of interferon regulatory factor 3 (IRF3) and expression of the antiviral beta interferon (IFN-β) gene. To identify the viral proteins responsible for NF-κB dependency, reassortant viruses were generated by reverse genetics. SC35 viruses containing the SC35M segment encoding neuraminidase (NA) were completely inert to the inhibitory effect of NF-κB, emphasizing the importance of the viral genotype for susceptibility to the antiviral functions of NF-κB. IMPORTANCE:This study addresses two different issues. First, we investigated the role of the host cell transcription factor NF-κB in IAV replication by genetic manipulation of IAVs by reverse genetics combined with targeted genome engineering of host cells using CRISPR-Cas9. The analysis of these two highly defined genetic systems indicated that the IAV genotype can influence whether NF-κB displays an antiviral function and thus might in part explain incoherent results from the literature. Second, we found that perturbation of NF-κB function greatly improved the growth of a nonadapted IAV, suggesting that NF-κB may contribute to the maintenance of the host species barrier.
journal_name
J Viroljournal_title
Journal of virologyauthors
Dam S,Kracht M,Pleschka S,Schmitz MLdoi
10.1128/JVI.00946-16subject
Has Abstractpub_date
2016-08-12 00:00:00pages
7980-90issue
17eissn
0022-538Xissn
1098-5514pii
JVI.00946-16journal_volume
90pub_type
杂志文章abstract::Two second-site mutations in Moloney murine leukemia virus envelope surface protein (SU) were previously shown to rescue infection of two different SU mutants, a fusion-defective point mutant and a fusion-defective modified SU that exhibits weak subunit association. We report here that they also rescue infection of a ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.23.11881-11885.2001
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doi:10.1128/jvi.74.20.9507-9514.2000
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journal_title:Journal of virology
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doi:10.1128/JVI.14.5.1288-1292.1974
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pub_type: 杂志文章
doi:10.1128/JVI.66.10.5929-5936.1992
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00317-09
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.5.3.293-298.1970
更新日期:1970-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.01581-07
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.2.4.365-375.1968
更新日期:1968-04-01 00:00:00
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doi:10.1128/JVI.78.16.8609-8614.2004
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00827-19
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.11.8923-8927.1997
更新日期:1997-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.5.1262-1267.1974
更新日期:1974-11-01 00:00:00
abstract::Experimental reverse genetic replacement of Epstein-Barr virus nuclear antigen 3A (EBNA3A) with a conditional mutant EBNA3A revealed that EBNA3A is critical for continued lymphoblastoid cell (LCL) growth. Wild-type (wt) EBNA3A expressed in the LCLs specifically sustained growth under nonpermissive conditions, whereas ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.16.10171-10179.2005
更新日期:2005-08-01 00:00:00
abstract::In-frame stop codons were introduced into the coding region of human immunodeficiency virus type 1 (HIV-1) transmembrane protein (gp41). Truncation of 147 amino acids from the carboxyl terminus of gp41 (TM709) significantly decreased the stability and cell surface expression of the viral Env proteins, while truncation...
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pub_type: 杂志文章
doi:10.1128/JVI.67.1.213-221.1993
更新日期:1993-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.56.3.969-977.1985
更新日期:1985-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03587-13
更新日期:2014-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.2.475-480.1986
更新日期:1986-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.3.863-871.1981
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.3.1055-1063.1981
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pub_type: 杂志文章
doi:10.1128/JVI.62.2.629-632.1988
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abstract::Examination of the interaction between human immunodeficiency virus (HIV) regulatory gene products and the host immune system is fundamental to understanding the pathogenesis of HIV and could reveal possible targets for therapeutic intervention in the treatment of AIDS. The HIV Tat gene is a potential candidate for th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.7622-7629.1995
更新日期:1995-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.14.8116-8126.2003
更新日期:2003-07-01 00:00:00
abstract::Epstein-Barr virus (EBV) in vivo is known to establish persistent infection in resting, circulating memory B cells and to productively replicate in plasma cells. Until now, the molecular mechanism of how EBV switches from latency to lytic replication in vivo was not known. Here, we report that the plasma cell differen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01055-07
更新日期:2007-12-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) tat protein functions at a much lower level in rodent cells than in human cells. This species-specific difference in trans activation appears to be due to the lack of a functional homolog of a human cofactor for tat in rodent cells. Using HIV-1 long terminal repeat-drive...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.9.4565-4567.1990
更新日期:1990-09-01 00:00:00
abstract::The ability to manipulate the genomes of herpesviruses is of eminent importance for obtaining insight into gene function and regulation of gene expression of these complex viruses. Here we report the use of in vivo overlap recombination to generate pseudorabies virus mutants. Cotransfection of up to five overlapping c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.6.2191-2195.1988
更新日期:1988-06-01 00:00:00
abstract::Unlike RNA viruses, most DNA viruses replicate their genomes with high-fidelity polymerases that rarely make base substitution errors. Nevertheless, experimental evolution studies have revealed rapid acquisition of adaptive mutations during serial passage of attenuated vaccinia virus (VACV). One way in which adaptatio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01053-20
更新日期:2020-08-31 00:00:00
abstract::NF-D is a ubiquitous nuclear factor that has been shown to bind specifically to a DNA element in the polyomavirus regulatory region. In this report, we demonstrate that NF-D is either identical or very similar to a transcription factor that has been variously named YY1, delta, NF-E1, UCRBP, or CF1. Moreover, we show t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.1433-1438.1996
更新日期:1996-03-01 00:00:00
abstract:UNLABELLED:The HIV-1 glycoprotein 41 promotes fusion of the viral membrane with that of the target cell. Structural, biochemical, and biophysical studies suggest that its membrane-proximal external region (MPER) may interact with the HIV-1 membrane and induce its disruption and/or deformation during the process. Howeve...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02151-14
更新日期:2014-11-01 00:00:00
abstract::The efficiency of processing of polyoma viral RNA and of its export from nucleus to cytoplasm was measured in primary mouse kidney cells by comparing the initial rates of incorporation of [3H]uridine into cytoplasmic and nuclear viral RNA. Appropriate methods of cell fractionation were chosen to maximize yields of cyt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.2.628-635.1981
更新日期:1981-02-01 00:00:00