Abstract:
UNLABELLED:Susceptibility to alphavirus infection is age dependent, and host maturation is associated with decreased virus replication and less severe encephalitis. To identify factors associated with maturation-dependent restriction of virus replication, we studied AP-7 rat olfactory bulb neuronal cells, which can differentiate in vitro. Differentiation was associated with a 150- to 1,000-fold decrease in replication of the alphaviruses Sindbis virus and Venezuelan equine encephalitis virus, as well as La Crosse bunyavirus. Differentiation delayed synthesis of SINV RNA and protein but did not alter the susceptibility of neurons to infection or virion maturation. Additionally, differentiation slowed virus-induced translation arrest and death of infected cells. Differentiation of uninfected AP-7 neurons was associated with changes in expression of antiviral genes. Expression of key transcription factors was increased, including interferon regulatory factor 3 and 7 (IRF-3 and IRF-7) and STAT-1, suggesting that neuronal maturation may enhance the capacity for antiviral signaling upon infection. IRF-7 produced by undifferentiated AP-7 neurons was exclusively the short dominant negative γ-isoform, while that produced by differentiated neurons was the full-length α-isoform. A similar switch in IRF-7 isoforms also occurred in the brains of maturing C57BL/6J mice. Silencing of IRF expression did not improve virus multiplication in differentiated neurons. Therefore, neuronal differentiation is associated with upregulation of transcription factors that activate antiviral signaling, but this alone does not account for maturation-dependent restriction of virus replication. IMPORTANCE:Viral encephalomyelitis is an important cause of age-dependent morbidity and mortality. Because mature neurons are not readily regenerated, recovery from encephalitis suggests that mature neurons utilize unique antiviral mechanisms to block infection and/or clear virus. To identify maturational changes in neurons that may improve outcome, we compared immature and mature cultured neurons for susceptibility to three encephalitic arboviruses and found that replication of Old World and New World alphaviruses and a bunyavirus was reduced in mature compared to immature neurons. Neuronal maturation was associated with increased baseline expression of interferon regulatory factor 3 and 7 mRNAs and production of distinct isoforms of interferon regulatory factor 7 protein. Overall, our studies identified maturational changes in neurons that likely contribute to assembly of immunoregulatory factors prior to infection, a more rapid antiviral response, increased resistance to virus infection, and improved survival.
journal_name
J Viroljournal_title
Journal of virologyauthors
Schultz KL,Vernon PS,Griffin DEdoi
10.1128/JVI.02394-14subject
Has Abstractpub_date
2015-01-01 00:00:00pages
48-60issue
1eissn
0022-538Xissn
1098-5514pii
JVI.02394-14journal_volume
89pub_type
杂志文章abstract::The simian virus 40 large T antigen is a promiscuous transcriptional activator of many viral and cellular promoters. We show that the promoter structure necessary for T antigen-mediated transcriptional activation is very simple. A TATA or initiator element is required, in addition to an upstream factor-binding site, w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.11.6682-6688.1993
更新日期:1993-11-01 00:00:00
abstract::Ground squirrel hepatitis virus (GSHV) is a small DNA virus, structurally and antigenically related to the human hepatitis B virus, which occurs naturally among certain wild populations of ground squirrels (P. L. Marion et al., Proc. Natl. Acad. Sci. U.S.A. 77:2941-2945, 1980). Serum from naturally infected animals wa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.1.366-373.1982
更新日期:1982-10-01 00:00:00
abstract::Feline leukemia viruses (FeLVs) belonging to interference subgroup C induce fatal anemia resembling human pure red cell aplasia (PRCA). Subgroup A FeLVs, although closely related genetically to FeLVs of subgroup C, do not induce PRCA. The determinants for PRCA induction by a molecularly cloned prototype subgroup C vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.9.5561-5568.1992
更新日期:1992-09-01 00:00:00
abstract::The nonstructural 4B (NS4B) protein of hepatitis C virus (HCV) plays a central role in the formation of the HCV replication complex. To gain insight into the role of charged residues for NS4B function in HCV RNA replication, alanine substitutions were engineered in place of 28 charged residues residing in the N- and C...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00858-11
更新日期:2011-08-01 00:00:00
abstract::The primary pathophysiologic finding of the viral disease known as Korean hemorrhagic fever, the etiological agent of which is Hantaan virus (HTV), is vascular instability. To investigate whether HTV was able to infect cells derived from human vascular tissue and alter their behavior, we infected in vitro primary adul...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.10.5929-5936.1992
更新日期:1992-10-01 00:00:00
abstract::RNA silencing is a potent means of antiviral defense in plants and animals. A hallmark of this defense response is the production of 21- to 24-nucleotide viral small RNAs via mechanisms that remain to be fully understood. Many viruses encode suppressors of RNA silencing, and some viral RNAs function directly as silenc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02339-06
更新日期:2007-03-01 00:00:00
abstract::The required activities of CD4(+) T cells and antibody against the virally encoded oncoprotein simian virus 40 (SV40) Tag have previously been demonstrated by our laboratory to be mediators in achieving antitumor responses and tumor protection through antibody-dependent cell-mediated cytotoxicity (ADCC). In this study...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01512-09
更新日期:2010-01-01 00:00:00
abstract::Cleavage of varicella-zoster virus DNA with the restriction endonucleases PstI, XbaI, and BglII resulted in 18, 22, and 20 fragments, respectively. Based on the molecular weights and molarities of these fragments, a molecular weight of 84 x 10(6) could be calculated for the varicella-zoster virus genome. In both the X...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.2.390-400.1981
更新日期:1981-08-01 00:00:00
abstract::10A1 murine leukemia virus can enter cells by using either of two different cell surface phosphate transport proteins, the gibbon ape leukemia virus receptor Glvr-1 (Pit-1) or the amphotropic retrovirus receptor Ram-1 (Pit-2). Glvr-1 and Ram-1 are widely expressed in different tissues, but the relative amounts of each...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.8.5564-5571.1996
更新日期:1996-08-01 00:00:00
abstract::Human cells infected with adenovirus type 2 (Ad2) or Ad5 require VAI RNA for efficient translation of viral mRNAs at late times after infection. The Ad5 mutant dl-sub720 synthesized neither virus-associated I (VAI) nor VAII RNAs, and infection of human cells with this mutant resulted in reduced virion polypeptide synt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.363-368.1986
更新日期:1986-11-01 00:00:00
abstract::A retrovirus endogenous to guinea pig cells was earlier shown to be morphologically similar to type B and type D prototype retroviruses. Molecular hybridization techniques were used to show that guinea pig virus nucleotide sequences are endogenous to both domestic (Cavia porcellus) and indigenous (Cavia aperea) guinea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.33.1.522-530.1980
更新日期:1980-01-01 00:00:00
abstract::Protein kinase activity is associated with both the extracellular and the occluded forms of Autographa californica nuclear polyhedrosis virus, a baculovirus. Serine and threonine are the predominant amino acids phosphorylated by the kinase activity associated with both viral forms; no phosphotyrosine was detected. The...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.1.275-278.1983
更新日期:1983-04-01 00:00:00
abstract::Profound alterations in host cell nuclear architecture accompany the lytic phase of Epstein-Barr virus (EBV) infection. Viral replication compartments assemble, host chromatin marginalizes to the nuclear periphery, cytoplasmic poly(A)-binding protein translocates to the nucleus, and polyadenylated mRNAs are sequestere...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01254-18
更新日期:2018-09-26 00:00:00
abstract::The role of autoimmunity in large-vessel vasculitis in humans remains unclear. We have previously shown that infection of gamma interferon receptor knockout (IFN-gamma R(-/-)) mice with gammaherpesvirus 68 (gamma HV68) results in severe inflammation of the large elastic arteries that is pathologically similar to the l...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.23.11304-11310.2000
更新日期:2000-12-01 00:00:00
abstract::Human papillomaviruses (HPVs) infect squamous epithelium and establish their genomes as episomes in proliferating basal cells. As infected cells differentiate, the viral DNA is amplified to high copy number and infectious virus is produced. Viral production has not yet been observed in vitro due to the inability of st...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.5.2254-2260.1991
更新日期:1991-05-01 00:00:00
abstract::Diseases of the nasopharyngeal epithelium due to Epstein-Barr virus (EBV) infection typically occur in chronic virus carriers with preexisting virus-specific antibodies. In vitro studies have shown that EBV-specific immunoglobulin A (IgA) promotes infection of human epithelial cells, otherwise refractory to EBV, via t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.1.519-526.1997
更新日期:1997-01-01 00:00:00
abstract::The specificity of binding of wheat germ ribosomes to mRNA was greatly altered by cleavage of the message. Fragmentation of reovirus mRNA allowed wheat germ ribosomes to bind and protect a variety of internal sequences which were not accessible to ribosomes in the intact message. In experiments using the polycistronic...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.3.748-756.1980
更新日期:1980-09-01 00:00:00
abstract::A majority of species B adenoviruses (Ads) use CD46 as their primary receptor; however, the precise mechanisms involved in the binding of different Ad types to CD46 have not been resolved. Although previous studies indicate close similarities between two members of species B2 Ads in their usage of CD46, our current in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00754-08
更新日期:2008-08-01 00:00:00
abstract::The poliovirus (PV) genome was manipulated by replacing its 2A-encoding sequence with the corresponding sequence of coxsackie B4 virus (CBV4) or human rhinovirus type 2 (HRV2). In vitro translation of the resulting chimeric PV genomes revealed a normal cis-cleavage activity for both heterologous 2A(pro) proteinases in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.7445-7452.1995
更新日期:1995-12-01 00:00:00
abstract::NK cells are key effectors of innate immunity and host survival during cytomegalovirus (CMV) infection. Innate murine CMV (MCMV) resistance in MA/My mice requires Ly49H/m157-independent H-2k-linked NK cell control. Here we show that replacement of MA/My H-2k with C57L H-2b susceptibility genes led to a remarkable loss...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00997-06
更新日期:2007-01-01 00:00:00
abstract::The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00045-17
更新日期:2017-04-28 00:00:00
abstract::Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier to successful infection. The adenovirus genome is packaged with protein...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01089-17
更新日期:2017-09-27 00:00:00
abstract::Vif(IIIB), which has been a standard model for the viral infectivity factor of human immunodeficiency virus type 1 (HIV-1), binds the cytidine deaminase APOBEC3G (A3G) and induces its degradation, thereby precluding its lethal incorporation into assembling virions. Additionally, Vif(IIIB) less efficiently degrades A3F...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01078-07
更新日期:2008-01-01 00:00:00
abstract::DNA of the avian hepadnavirus, duck hepatitis B virus, was found to be integrated at low abundance into the cellular DNA extracted from the livers of infected ducklings. The frequency of integration was estimated to be at least one viral genome per 10(3) to 10(4) cells by 6 days postinfection. The structures of virus-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.12.9710-9717.1999
更新日期:1999-12-01 00:00:00
abstract:UNLABELLED:Protease is essential for retroviral replication, and protease inhibitors (PI) are important for treating HIV infection. HIV-2 exhibits intrinsic resistance to most FDA-approved HIV-1 PI, retaining clinically useful susceptibility only to lopinavir, darunavir, and saquinavir. The mechanisms for this resistan...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01772-15
更新日期:2015-11-11 00:00:00
abstract::We have selected an HXB2 variant which can replicate in the presence of a neutralizing human serum. Sequencing of the gp120 region of the env gene from the variant and parental viruses identified a single amino acid substitution in the third conserved region of gp120 at residue 375 (AGT-->AAT, Ser-->Asn; designated 37...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.9.5216-5225.1993
更新日期:1993-09-01 00:00:00
abstract::The wild mouse ecotropic retrovirus, Cas-Br-E, induces progressive, noninflammatory spongiform neurodegenerative disease in susceptible mice. Functional genetic analysis of the Cas-Br-E genome indicates that neurovirulence maps to the env gene, which encodes the surface glycoprotein responsible for binding and fusion ...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/jvi.74.3.1558-1565.2000
更新日期:2000-02-01 00:00:00
abstract::Apoptosis is a type of controlled cell death that is essential for development and tissue homeostasis. It also serves as a robust host response against infection by many viruses. The capacity of neurotropic viruses to induce apoptosis strongly correlates with virulence. However, the precise function of apoptosis in vi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01931-13
更新日期:2013-12-01 00:00:00
abstract::9-([2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine (BW B759U) is more potent and has a more prolonged inhibitory effect against Epstein-Barr virus (EBV) in vitro than does acyclovir (ACV). To assess the mechanism of this difference, we first compared the extent of phosphorylation of the two drugs in superinfected Ra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.569-573.1986
更新日期:1986-11-01 00:00:00
abstract::The DA strain of Theiler's virus, a murine picornavirus, causes a persistent infection of glial cells of the white matter of the spinal cord, associated with chronic inflammation and primary demyelination. The GDVII strain causes an acute fatal grey matter encephalomyelitis. We characterized the target cells of GDVII ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.5.3197-3200.1995
更新日期:1995-05-01 00:00:00