Abstract:
:Viruses in the family Coronaviridae, within the order Nidovirales, are etiologic agents of a range of human and animal diseases, including both mild and severe respiratory diseases in humans. These viruses encode conserved replicase and structural proteins as well as more diverse accessory proteins, encoded in the 3' ends of their genomes, that often act as host cell antagonists. We previously showed that 2',5'-phosphodiesterases (2',5'-PDEs) encoded by the prototypical Betacoronavirus, mouse hepatitis virus (MHV), and by Middle East respiratory syndrome-associated coronavirus antagonize the oligoadenylate-RNase L (OAS-RNase L) pathway. Here we report that additional coronavirus superfamily members, including lineage A betacoronaviruses and toroviruses infecting both humans and animals, encode 2',5'-PDEs capable of antagonizing RNase L. We used a chimeric MHV system (MHVMut) in which exogenous PDEs were expressed from an MHV backbone lacking the gene for a functional NS2 protein, the endogenous RNase L antagonist. With this system, we found that 2',5'-PDEs encoded by the human coronavirus HCoV-OC43 (OC43; an agent of the common cold), human enteric coronavirus (HECoV), equine coronavirus (ECoV), and equine torovirus Berne (BEV) are enzymatically active, rescue replication of MHVMut in bone marrow-derived macrophages, and inhibit RNase L-mediated rRNA degradation in these cells. Additionally, PDEs encoded by OC43 and BEV rescue MHVMut replication and restore pathogenesis in wild-type (WT) B6 mice. This finding expands the range of viruses known to encode antagonists of the potent OAS-RNase L antiviral pathway, highlighting its importance in a range of species as well as the selective pressures exerted on viruses to antagonize it.IMPORTANCE Viruses in the family Coronaviridae include important human and animal pathogens, including the recently emerged viruses severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome-associated coronavirus (MERS-CoV). We showed previously that two viruses within the genus Betacoronavirus, mouse hepatitis virus (MHV) and MERS-CoV, encode 2',5'-phosphodiesterases (2',5'-PDEs) that antagonize the OAS-RNase L pathway, and we report here that these proteins are furthermore conserved among additional coronavirus superfamily members, including lineage A betacoronaviruses and toroviruses, suggesting that they may play critical roles in pathogenesis. As there are no licensed vaccines or effective antivirals against human coronaviruses and few against those infecting animals, identifying viral proteins contributing to virulence can inform therapeutic development. Thus, this work demonstrates that a potent antagonist of host antiviral defenses is encoded by multiple and diverse viruses within the family Coronaviridae, presenting a possible broad-spectrum therapeutic target.
journal_name
J Viroljournal_title
Journal of virologyauthors
Goldstein SA,Thornbrough JM,Zhang R,Jha BK,Li Y,Elliott R,Quiroz-Figueroa K,Chen AI,Silverman RH,Weiss SRdoi
10.1128/JVI.02201-16subject
Has Abstractpub_date
2017-02-14 00:00:00issue
5eissn
0022-538Xissn
1098-5514pii
JVI.02201-16journal_volume
91pub_type
杂志文章abstract::The immunosuppressant drug rapamycin blocks progression of the cell cycle at G1 in mammalian cells and yeast. We recently showed that rapamycin inhibits both in vitro and in vivo cap-dependent, but not cap-independent, translation. This inhibition is causally related to reduced phosphorylation and consequent activatio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.12.8993-8996.1996
更新日期:1996-12-01 00:00:00
abstract:UNLABELLED:Virions vary in size by at least 4 orders of magnitude, yet the evolutionary forces responsible for this enormous diversity are unknown. We document a significant allometric relationship, with an exponent of approximately 1.5, between the genome length and virion volume of viruses and find that this relation...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00362-14
更新日期:2014-06-01 00:00:00
abstract::The configuration of latent varicella-zoster virus (VZV) DNA was analyzed by PCR. Template DNA for both internal and terminal VZV primers was present in a 1:1 ratio in ganglionic DNA, compared with a 15:1 ratio in DNA extracted from VZV virions, indicating that the VZV genomic termini are adjacent in latently infected...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.8151-8154.1995
更新日期:1995-12-01 00:00:00
abstract::The interaction of the human immunodeficiency virus type 1 (HIV-1) nucleoprotein complex with the cell nuclear import machinery is necessary for viral replication in macrophages and for the establishment of infection in quiescent T lymphocytes. The karyophilic properties of two viral proteins, matrix (MA) and Vpr, are...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.2.1027-1032.1996
更新日期:1996-02-01 00:00:00
abstract::Activation of microglia and astroglia is seen in many neurodegenerative diseases including prion diseases. Activated glial cells produce cytokines as a protective response against certain pathogens and as part of the host inflammatory response to brain damage. In addition, cytokines might also exacerbate tissue damage...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01413-09
更新日期:2009-11-01 00:00:00
abstract::Chick embryo cells became more sensitive to the action of interferon the longer they remained in culture. This phenomenon was found even before confluency had been reached. The relative insensitivity of newly seeded cells was not due to a loss of receptors. Cells synthesizing deoxyribonucleic acid (DNA) at a high rate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.4.1.7-11.1969
更新日期:1969-07-01 00:00:00
abstract::A tumorigenic line of mouse cells transformed by the nononcogenic murine K papovavirus was established and characterized. Tumor-bearing animals produced antibody specific for K virus-transformed cells; the K virus T antiserum did not react with polyomavirus-transformed cells. Immunoprecipitation of the T antigen in th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.954-956.1984
更新日期:1984-06-01 00:00:00
abstract::The cellular immune response contributes to viral clearance as well as to liver injury in acute and chronic hepatitis C virus (HCV) infection. An immunodominant determinant frequently recognized by liver-infiltrating and circulating CD8(+) T cells of HCV-infected patients is the HCV(NS3-1073) peptide CVNGVCWTV. Using ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.23.11392-11400.2001
更新日期:2001-12-01 00:00:00
abstract::In this paper, we report that the DNA of bovine mammillitis virus (BMV) consists of two covalently linked components that are 71.5 x 10(6) and 15.7 x 10(6) in molecular weight and designated L and S, respectively. We further report that the BMV DNA consists of four equimolar populations differing only in the orientati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.25.1.395-407.1978
更新日期:1978-01-01 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 murine polyomavirus (Py) enters mouse fibroblasts and kidney epithelial cells via an endocytic pathway that is caveola-independent (as well as clathrin-independent). In contrast, uptake of simian virus 40 into the same cells is dependent on caveola. Following the initial uptake of Py, both microtubules and microfi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.4.2615-2622.2003
更新日期:2003-02-01 00:00:00
abstract::Adenovirus type 2 (Ad2)-transformed hamster and rat cells are susceptible to lysis by natural killer (NK) cells from the host of origin and are nontumorigenic in immunocompetent hamsters and rats, respectively. These NK-cell-susceptible, virus-transformed cells are, however, highly tumorigenic in athymic (nude) mice--...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.7.2155-2161.1987
更新日期:1987-07-01 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
abstract::We report a Sendai virus (SeV) vector system for expression of major histocompatibility complex (MHC) class I/peptide complexes. We cloned the extracellular domain of a human MHC class I heavy chain, HLA-A*2402, and human beta-2 microglobulin (beta2m) fused with HLA-A*2402-restricted human immunodeficiency virus type ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.23.11982-11988.2002
更新日期:2002-12-01 00:00:00
abstract::We have selected neutralization escape mutants by using a monoclonal antibody (nt-MAb) against a sequential epitope between amino acids 93 through 104 (neutralization antigenic site I) of poliovirus type 1 Mahoney. The majority of mutants were also resistant against five strain-specific nt-MAbs which recognized confor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.5.1845-1848.1988
更新日期:1988-05-01 00:00:00
abstract::Since the number of human cases of infection with avian H5N1 influenza viruses is ever increasing, a pandemic outbreak caused by these viruses is feared. Therefore, in addition to virus-specific antibodies, there is considerable interest in immune correlates of protection against these viruses, which could be a target...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02694-07
更新日期:2008-06-01 00:00:00
abstract::There are no known RNA viruses that infect Archaea. Filling this gap in our knowledge of viruses will enhance our understanding of the relationships between RNA viruses from the three domains of cellular life and, in particular, could shed light on the origin of the enormous diversity of RNA viruses infecting eukaryot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.07196-11
更新日期:2012-05-01 00:00:00
abstract::Strategies were developed to insert the neo resistance marker into the junction between L DNA and the right terminal repetitive H DNA of herpesvirus saimiri. Recombinant viruses were selectable in permissive epithelioid cultures. The human T-cell line Jurkat could be infected persistently with the Neor virus; the cell...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.4.1818-1821.1989
更新日期:1989-04-01 00:00:00
abstract::We have found that interleukin-4 (IL-4) abrogated constitutive beta interferon (IFN-beta) synthesis in mouse macrophages. Analysis of endogenous IFN mRNA by reverse transcription-PCR clearly documented the presence of IFN-beta but not of IFN-alpha transcripts in RNA from bone marrow-derived macrophages (BMM). Culture ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.10.6763-6766.1994
更新日期:1994-10-01 00:00:00
abstract::The membrane glycoproteins G1 and G2 of Uukuniemi virus, a member of the Bunyaviridae family, are cotranslationally cleaved from a common precursor in the endoplasmic reticulum (ER). Here, we show that newly made G1 and G2 associate transiently with calnexin and calreticulin, two lectins involved in glycoprotein foldi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.7.6123-6127.1999
更新日期:1999-07-01 00:00:00
abstract::ZEBRA is an Epstein-Barr virus (EBV) transcriptional activator that mediates a genetic switch between the latent and lytic states of the virus by binding to the promoters of genes involved in lytic DNA replication and activating their transcription. A computer survey revealed that 9 of 23 potential or known ZEBRA-resp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.8.4803-4813.1992
更新日期:1992-08-01 00:00:00
abstract::The three primary capsid proteins (A, B, and C) of adeno-associated viruses have been shown previously to contain overlapping amino acid sequences (R. McPherson and J. Rose, J. Virol. 46:523-529, 1983). In the present study we demonstrate definitively that these proteins are encoded in the right half of the adeno-asso...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.52.2.591-597.1984
更新日期:1984-11-01 00:00:00
abstract::Encephalomyocarditis (EMC) virus (K-2 strain) was separated into two distinct peaks of optical density by chromatography on calcium phosphate, eluting at 0.17 and 0.31 m, respectively. The virus in these peaks could not be distinguished by infectivity (plaque-forming units), hemagglutinin activity, electron microscopi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.1.2.308-316.1967
更新日期:1967-04-01 00:00:00
abstract::Valproic acid (VPA) is a short-chain fatty acid commonly used for treatment of neurological disorders. As VPA can interfere with cellular lipid metabolism, its effect on the infection of cultured cells by viruses of seven viral families relevant to human and animal health, including eight enveloped and four nonenvelop...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01717-10
更新日期:2011-02-01 00:00:00
abstract::The intracellular assembly of the transmissible gastroenteritis coronavirus (TGEV) was studied in infected swine testis (ST) cells at different postinfection times by using ultrathin sections of conventionally embedded infected cells, freeze-substitution, and methods for detecting viral proteins and RNA at the electro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.5.4022-4031.1998
更新日期:1998-05-01 00:00:00
abstract::Translation of early RNA specific for the leftmost early region 1 of adenovirus type 5 DNA in a rabbit reticulocyte cell-free system resulted in the synthesis of proteins with the following molecular weights: 65,000 (65K), 54K, 42 to 34K, 29K, 25K, 19K, and 18K. All of these proteins could be immunoprecipitated with h...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.1.524-529.1981
更新日期:1981-01-01 00:00:00
abstract::Temperature-sensitive (ts) mutants of the T4 phage rII gene were islated and used in temperature shift experiments that revelaed two different expressions for the normal rII (rII+) gene function in vivo: (i) an early expression (0 to 12 min postinfection at 30 C) that prevents restriction of T4 growth in Escherichia c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.4.974-981.1975
更新日期:1975-10-01 00:00:00
abstract::Hepatitis delta antigen (HDAg) is the only known protein of hepatitis delta virus and was previously shown to localize in the nucleoplasm of infected liver cells. In this study, nuclear localization signals of HDAg were defined by expressing various domains of the antigen in both hepatic and nonhepatic cells as beta-g...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.10.6019-6027.1992
更新日期:1992-10-01 00:00:00
abstract::Adeno-associated virus (AAV) is a human parvovirus currently being developed as a vector for gene therapy applications. Because the gene transfer vector commonly retains only the AAV terminal repeats, propagation of recombinant AAV (rAAV) requires that the viral replication (Rep) and capsid (Cap) proteins be supplied ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.3.1897-1905.1997
更新日期:1997-03-01 00:00:00
abstract::To identify retroviral antigenic determinants recognized by CD4+ T helper cells during tumor rejection, we established four noncytolytic, helper-type, CD4+ T-cell clones by limiting dilution cultures of mixed lymphocyte-tumor cultures from mice immune to a Friend virus-induced tumor, FBL-3. Among these, three T helper...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.8.4533-4542.1993
更新日期:1993-08-01 00:00:00