Abstract:
:Alphavirus infection of fibroblastic cell types in vitro inhibits host cell translation and transcription, leading to suppression of interferon alpha/beta (IFN-α/β) production. However, the effect of infection upon myeloid cells, which are often the first cells encountered by alphaviruses in vivo, is unclear. Previous studies demonstrated an association of systemic IFN-α/β production with myeloid cell infection efficiency. Murine infection with wild-type Venezuelan equine encephalitis virus (VEEV), a highly myeloid-cell-tropic alphavirus, results in secretion of very high systemic levels of IFN-α/β, suggesting that stress responses in responding cells are active. Here, we infected myeloid cell cultures with VEEV to identify the cellular source of IFN-α/β, the timing and extent of translation and/or transcription inhibition in infected cells, and the transcription factors responsible for IFN-α/β induction. In contrast to fibroblast infection, myeloid cell cultures infected with VEEV secreted IFN-α/β that increased until cell death was observed. VEEV inhibited translation in most cells early after infection (<6 h postinfection [p.i.]), while transcription inhibition occurred later (>6 h p.i.). Furthermore, the interferon regulatory factor 7 (IRF7), but not IRF3, transcription factor was critical for IFN-α/β induction in vitro and in sera of mice. We identified a subset of infected Raw 264.7 myeloid cells that resisted VEEV-induced translation inhibition and secreted IFN-α/β despite virus infection. However, in the absence of IFN receptor signaling, the size of this cell population was diminished. These results indicate that IFN-α/β induction in vivo is IRF7 dependent and arises in part from a subset of myeloid cells that are resistant, in an IFN-α/β-dependent manner, to VEEV-induced macromolecular synthesis inhibition.IMPORTANCE Most previous research exploring the interaction of alphaviruses with host cell antiviral responses has been conducted using fibroblast lineage cell lines. Previous studies have led to the discovery of virus-mediated activities that antagonize host cell antiviral defense pathways, such as host cell translation and transcription inhibition and suppression of STAT1 signaling. However, their relevance and impact upon myeloid lineage cell types, which are key responders during the initial stages of alphavirus infection in vivo, have not been well studied. Here, we demonstrate the different abilities of myeloid cells to resist VEEV infection compared to nonmyeloid cell types and begin to elucidate the mechanisms by which host antiviral responses are upregulated in myeloid cells despite the actions of virus-encoded antagonists.
journal_name
J Viroljournal_title
Journal of virologyauthors
Bhalla N,Gardner CL,Downs SN,Dunn M,Sun C,Klimstra WBdoi
10.1128/JVI.00872-19subject
Has Abstractpub_date
2019-11-26 00:00:00issue
24eissn
0022-538Xissn
1098-5514pii
JVI.00872-19journal_volume
93pub_type
杂志文章abstract::Cellular and viral factors participate in the replication cycle of rotavirus. We report that the guanine nucleotide exchange factor GBF1, which activates the small GTPase Arf1 to induce COPI transport processes, is required for rotavirus replication since knocking down GBF1 expression by RNA interference or inhibiting...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01062-19
更新日期:2019-09-12 00:00:00
abstract::Natural killer (NK) cells derived from the human female reproductive tract (FRT) are phenotypically and functionally distinct from those obtained from peripheral blood. Because the FRT is a primary site of human immunodeficiency virus type 1 (HIV-1) infection in women, we determined whether soluble factors secreted by...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00562-09
更新日期:2009-11-01 00:00:00
abstract::Exosomes are small vesicles secreted from cells that participate in intercellular communication events. Accumulating evidence demonstrates that host exosome pathways are hijacked by viruses and that virally modified exosomes contribute to virus spread and immune evasion. In the case of tumor viruses, recent findings s...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.02470-14
更新日期:2015-05-01 00:00:00
abstract::The NS5A protein of hepatitis C virus (HCV) plays an important but undefined role in viral RNA replication. NS5A has been proposed to be a three-domain protein, and the crystal structure of the well-conserved amino-terminal domain I has been determined. The remaining two domains of NS5A, designated domains II and III,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00328-07
更新日期:2008-02-01 00:00:00
abstract::The first step in the replication of the plus-stranded poliovirus RNA is the synthesis of a complementary minus strand. This process is initiated by the covalent attachment of UMP to the terminal protein VPg, yielding VPgpU and VPgpUpU. We have previously shown that these products can be made in vitro in a reaction th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.22.10359-10370.2000
更新日期:2000-11-01 00:00:00
abstract::The genome-length, dicistronic mRNA of the double-stranded RNA fungal virus Helminthosporium victoriae virus 190S (genus Victorivirus, family Totiviridae) contains two long open reading frames (ORFs) that overlap in the tetranucleotide AUGA. Translation of the downstream ORF, which encodes the RNA-dependent RNA polyme...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00364-11
更新日期:2011-07-01 00:00:00
abstract::The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) sequesters TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures to inhibit the phosphorylation and nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3) and subsequent interferon beta (IFN-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00706-18
更新日期:2018-09-12 00:00:00
abstract::In various positive-sense single-stranded RNA viruses, a low-fidelity viral RNA-dependent RNA polymerase (RdRp) confers attenuated phenotypes by increasing the mutation frequency. We report a negative-sense single-stranded RNA virus RdRp mutant strain with a mutator phenotype. Based on structural data of RdRp, rationa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00834-19
更新日期:2019-10-29 00:00:00
abstract::RNA from adenovirus 2-infected KB cells was annealed in liquid with RNA in vast excess to viral heavy (l) and light (r) 32P-labeled DNA strands. Hybridization kinetics were analyzed by computer to estimate the number of viral RNA abundance classes, their relative concentrations, and the fraction of each DNA strand fro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.20.2.465-477.1976
更新日期:1976-11-01 00:00:00
abstract::Therapeutic vaccination has the potential to boost immune responses and enhance viral control during chronic infections. However, many therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral T-cell responses is not always observed. To examine these issues, we studied t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.14.8960-8968.2005
更新日期:2005-07-01 00:00:00
abstract::The src genes of different Rous sarcoma virus (RSV) strains have been reported to be highly conserved by some investigators using RNA-cDNA hybridization, whereas others using oligonucleotide, peptide, and serological analyses have judged src genes to be variable in 30 to 50% of the respective markers. Moreover, distin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.3.758-776.1981
更新日期:1981-09-01 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) infection results in the disruption of ND10 (also called nuclear bodies, PODs, or PML-associated bodies), which are nuclear matrix domains of unknown function present in mammalian cells. After ND10 disruption, viral transcription and DNA replication occur in globular nuclear domains...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.12.10100-10107.1998
更新日期:1998-12-01 00:00:00
abstract::Efforts to induce broadly reactive immunity against human immunodeficiency virus type 1 (HIV-1) have been impaired by the extent of sequence variation exhibited by this lentivirus. Cytotoxic T lymphocytes (CTL) specific for other viruses such as influenza virus have been shown to mediate immunity against divergent vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.5.3145-3153.1994
更新日期:1994-05-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) encodes specific trafficking signals within its long cytoplasmic tail (CT) that regulate incorporation into HIV-1 particles. Rab11-family interacting protein 1C (FIP1C) and Rab14 are host trafficking factors required for Env particle incorpora...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01893-17
更新日期:2018-02-12 00:00:00
abstract::The relationship between immunosenescence and the host response to virus infection is poorly understood at the molecular level. Two different patterns of pulmonary host responses to virus were observed when gene expression profiles from severe acute respiratory syndrome coronavirus (SARS-CoV)-infected young mice that ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00489-08
更新日期:2008-10-01 00:00:00
abstract::Assembly of hepatitis delta virus (HDV) in infected human hepatocytes involves association of the 1,679- nucleotide single-stranded genomic RNA (deltaRNA) with multiple copies of both small and large forms of the delta protein (deltaAg) to form a ribonucleoprotein particle which in turn interacts with envelope protein...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.8.3709-3719.2002
更新日期:2002-04-01 00:00:00
abstract::Varicella-zoster virus (VZV) is a highly species-specific herpesvirus that targets sensory ganglionic neurons. This species specificity has limited the study of many aspects of VZV pathogenesis, including neuronal infection. We report development of a highly efficient neuroblastoma cell model to study productive VZV i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00515-11
更新日期:2011-08-01 00:00:00
abstract::Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 genome encodes the Tax protein that plays essential regulatory roles in HTLV-1 replication and oncogenic transformation of T lymphocytes....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02006-13
更新日期:2013-12-01 00:00:00
abstract::Retrovirus particles each contain two copies of the viral genome in the form of a noncovalently linked RNA dimer. Earlier studies have mapped a cis-acting region near the 5' end of the human immunodeficiency virus type 1 (HIV-1) genome, termed the psi locus, which appears essential for initiation of genomic dimerizati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.5.3407-3414.1997
更新日期:1997-05-01 00:00:00
abstract::Natural killer T (NKT) cells are unique T lymphocytes that recognize CD1d-bound lipid antigens and play an important role in both innate and acquired immune responses against infectious diseases and tumors. We have already shown that a vesicular stomatitis virus (VSV) infection results in the rapid inhibition of murin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00881-08
更新日期:2008-12-01 00:00:00
abstract::The ability of vaccinia virus to replicate in HeLa cells which had been previously infected with adenovirus type 2 (Ad2) was studied in order to gain insight into the mechanism by which adenovirus inhibits the expression of host cell functions. Vaccinia virus was employed in these studies because it replicates in the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.2.208-213.1971
更新日期:1971-02-01 00:00:00
abstract::Expression of the region of the feline calicivirus (FCV) ORF1 encoded by nucleotides 3233 to 4054 in an in vitro rabbit reticulocyte system resulted in synthesis of an active proteinase that specifically processes the viral nonstructural polyprotein. Site-directed mutagenesis of the cysteine (Cys1193) residue in the p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.8.6626-6633.1999
更新日期:1999-08-01 00:00:00
abstract::The 72-kDa immediate early 1 (IE1) protein encoded by human cytomegalovirus (hCMV) is a nuclearly localized promiscuous regulator of viral and cellular transcription. IE1 has long been known to associate with host mitotic chromatin, yet the mechanisms underlying this interaction have not been specified. In this study,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02606-13
更新日期:2014-01-01 00:00:00
abstract::A strategy involving polymerase chain reaction amplification of cDNAs was designed to study the expression of the hamster polyomavirus (HaPV) early region in HaPV-transformed rat fibroblasts, productively HaPV-infected cells, and HaPV-induced lymphoma. We identified three mRNAs resulting from alternative splicing of o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.4.2495-2504.1992
更新日期:1992-04-01 00:00:00
abstract::The morphology and development of four members of the reticuloendotheliosis virus group were studied by transmission electron microscopy. Virions of duck spleen necrosis virus, duck infectious anemia virus, chicken syncytial virus, and reticuloendotheliosis virus strain T are sperical with a diameter of approximately ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.4.1027-1038.1975
更新日期:1975-10-01 00:00:00
abstract::The immune response to viral glycoproteins is often directed against conformation- and/or glycosylation-dependent structures; synthetic peptides and bacterially expressed proteins are inadequate probes for the mapping of such epitopes. This report describes a retroviral vector system that presents such native epitopes...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.1.400-410.1994
更新日期:1994-01-01 00:00:00
abstract::Regulation of immediate-early gene expression in human cytomegalovirus is subject to complex controls. The major immediate-early (mIE) gene is regulated by both positive and negative regulatory signals, including autoregulation mediated by a cis-repressive sequence. A second immediate-early gene, the US3 gene, is tran...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5362-5367.1995
更新日期:1995-09-01 00:00:00
abstract::Murine gammaherpesvirus 68 (gammaHV68; also known as MHV-68) can establish a latent infection in both inbred and outbred strains of mice and, as such, provides a tractable small-animal model to address mechanisms and cell types involved in the establishment and maintenance of chronic gammaherpesvirus infection. Latenc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.15.8310-8321.2003
更新日期:2003-08-01 00:00:00
abstract::Identification of cellular receptors used by coronavirus (CoV) entry into the host cells is critical to an understanding of pathogenesis and to development of intervention strategies. The fourth CoV genus, Deltacoronavirus, evolutionarily related to the Gammacoronavirus, has just been defined recently. In the current ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00318-18
更新日期:2018-05-29 00:00:00
abstract::The initial wave of swine-origin influenza A virus (pandemic H1N1/09) in the United States during the spring and summer of 2009 also resulted in an increased vigilance and sampling of seasonal influenza viruses (H1N1 and H3N2), even though they are normally characterized by very low incidence outside of the winter mon...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00018-10
更新日期:2010-06-01 00:00:00