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At least 343 records · Page 19Linked to original sources
PubMed1985

Nucleotide sequences responsible for generation of internally deleted Sendai virus defective interfering genomes.

The deletion points of four internally deleted defective interfering (DI) RNA species (7a, 7b, 7c, and 7d) that reside in a single Sendai virus strain were defined by nucleotide sequencing. DI RNA 7a (Mr 1.24 x 10(6)) retained the entire NP gene with the complete NP protein-coding sequence, except for the last two U residues of the polyadenylation signal, fused to an 1800-nucleotide sequence comprising 5'-terminal genome and adjacent L gene sequences. DI RNA 7b (Mr, 0.70 x 10(6)) consisted of 100 3'-terminal nucleotides fused to 1900 5'-terminal bases; the deletion point in the NP gene precedes the NP protein initiation codon. DI RNA 7c (Mr 0.55 x 10(6)) retained 420 3'-terminal and 1150 5'-terminal nucleotides. The sequence just downstream of the sequenced deletion site is M gene specific, indicating that 7c arose from at least two deletion events and that it comprises NP, M, and L gene fragments. Transcription of RNA 7c could yield an MRNA encoding a fusion protein with a 14,000 Mr (N-terminal NP sequence fused to out of frame M-specific amino acids). DI RNA 7d (Mr 0.92 x 10(6)) retained 1027 3'-terminal nucleotides fused to 1600 bases from the 5'-terminus. It has an open reading frame for a 33,000 Mr N-terminal NP protein fragment. Nucleotide sequences flanking each deletion and just downstream of the NP gene deletion site suggested that these DI genomes were generated by a copy-choice mechanism, involving polymerase jumping during replication of negative polarity virus genome templates. In this process, the termination and reinitiation of RNA synthesis would involve recognition of sequences that regulate virus genome transcription and replication.

Base Sequence↗
PubMed1985

Establishment of cell lines persistently infected with foot-and-mouth disease virus.

Cell lines persistently infected with foot-and-mouth disease virus (FMDV) have been established by growth of BHK-21 (c-13) or IBRS-2 (c-26) that survived standard cytolytic infections with FMDV. They maintain cytoplasmic FMDV RNA sequences, as shown by dot blot hybridization tests, using cloned FMDV cDNA as probes. Cell line C1-BHK-Rc1 was derived by infection of cloned BHK-21 c1 cells and plaque-purified FMDV C-S8 c1. Indirect immunofluorescence assays indicated the presence of FMDV antigens. It was resistant to superinfection by FMDV C-S8 c1, O-S7, or A5, but not by encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV), or Semliki forest virus (SFV). Infectious FMDV was detected in the culture medium only up to cell passage 65. The virus isolated from C1-BHK-Rc1 cells showed decreased plaque size and diminished yield in infections at 42 degrees. Multiple mutations in the intracellular FMDV RNA have been detected by T1 oligonucleotide fingerprinting of genomic RNA segments hybridized to FMDV cDNA fragments. At late cell passages, when no infectious FMDV is detected, cells continue to express viral antigens and FMDV RNAs with deletions of up to 3 kb have been identified by Northern blot analysis. We conclude that persistent infections of cell cultures with FMDV are readily established and that multiple genetic and phenotypic variations occur in the virus during persistence.

Animals↗
PubMed1986

The overproduction and characterization of the bacteriophage Mu regulatory DNA-binding protein ner.

The bacteriophage Mu ner gene has been cloned under the control of the lacUV5 promoter in the expression vector pOP95-15. The gene products of the recombinant plasmid, pUD88, visualized by in vitro coupled transcription-translation, are the bacteriophage Mu ner protein (8 kDa) and a 23 KDa protein consisting of the amino terminus of gpA (Mu transposase) fused to the carboxy terminus of beta-lactamase. DNA-binding activity was measured by the retardation of migration of a 32P-labeled DNA restriction fragment (containing the presumed ner-binding sites) in polyacrylamide gels. We have demonstrated specific association of ner to its binding sites to occur within 30 sec after the addition of impure extracts of ner overproducing cells. Much of this binding was dissociated within 30 sec by competition with a 20-fold molar excess of specific unlabeled DNA restriction fragment, but was resistant to dissociation when competed with unlabeled heterologous DNA for as long as 45 min at 37 degrees. By adapting a method for DNA-footprinting using impure extracts of ner overproducing cells, we were able to determine that the ner-binding sites are located between nucleotides 1026 and 1058 from the Mu left end. These results support the hypothesis that ner is similar to the cro regulatory protein from bacteriophage lambda and acts to regulate Mu early gene expression and the choice between lytic and lysogenic development.

Bacteriophage mu↗
PubMed1988

Expression of alfalfa mosaic virus cDNA1 and 2 in transgenic tobacco plants.

Chimeric genes composed of DNA complementary to alfalfa mosaic virus (AIMV) RNAs 1 or 2, the CaMV 35 S promoter, and the nos polyadenylation signal were transferred to the genome of Nicotiana tabacum cv. Samsun NN by means of the Agrobacterium tumefaciens transformation system. Transformants contained intact copies of the viral genes and accumulated transcripts of approximately the size predicted from the cloning procedure. Using antisera raised against synthetic peptides corresponding to the C-terminal parts of AIMV P1 and P2, it was not possible to detect viral translation products in the transformants. However, transgenic protoplasts containing cDNA1 were able to complement an infection by the AIMV nucleoproteins containing RNAs 2 and 3, indicating that biologically active P1 accumulates in these protoplasts. Upon inoculation with AIMV strains 425 or YSMV, the cDNA1- and cDNA2-transformed plants became infected to a level similar to that of nontransformed or vector-transformed control plants.

DNA↗
PubMed1988

Time course of virus-specific macromolecular synthesis during rubella virus infection in Vero cells.

Virus specific macromolecular synthesis was studied in Vero cells infected with plaque-purified rubella virus under one-step multiplication conditions. Under these conditions, the rate of virus production was found to increase rapidly until 24 hr postinfection after which time the rate of virus production rose more slowly, reaching a peak level at 48 hr postinfection. This peak rate of virus production was maintained through 72 hr postinfection. A majority of the cells remained alive through 96 hr postinfection, although a 20 to 30% decrease in the number of living cells occurred between 24 and 48 hr postinfection, the time period at which cytopathic effect was first observed. The virus structural proteins were first detected intracellularly at 16 hr postinfection. The rate of synthesis of these proteins was already maximal at 16 hr postinfection and remained constant through 48 hr postinfection. By immunofluorescence, cells expressing virus proteins were first observed at 12 hr postinfection. At 24 hr postinfection, 35 to 50% of the cells in the infected culture were exhibiting immunofluorescence, at 36 hr postinfection, 65 to 90% of the cells were exhibiting immunofluorescence, and at 48 hr postinfection, all of the cells were exhibiting immunofluorescence. The virus genomic and subgenomic RNA species were first detectable by 12 hr postinfection. The rate of synthesis of both of these species peaked at 26 hr postinfection. Rubella virus infection was found to have no effect on total cell RNA synthesis. However, a modest inhibition of total cell protein synthesis which reached 40% by 48 hr postinfection was observed. When Northern analysis of RNA extracted from infected cells was performed, a negative-polarity, virus-specific RNA probe hybridized only to the virus genomic and subgenomic RNA species. A positive-polarity, virus-specific RNA probe hybridized predominantly to a negative-polarity RNA of genome length indicating that both the genomic and subgenomic RNAs are synthesized from a genome-length negative-polarity template. Defective interfering (DI) RNAs were not detected in infected cells through 96 hr postinfection or in cells onto which virus released through 96 hr postinfection was passaged. Thus, the generation of DI particles by rubella virus appears to play no role in the slow, noncytopathic replication of this virus or in the ability of rubella virus-infected cells to survive for extended periods of time.

Animals↗
PubMed1988

Induction of an antiviral state by interferon in the absence of elevated levels of 2,5-oligo(A) synthetase and eIF-2 kinase.

A series of clones has been derived from an interferon-resistant murine cell line, Ltk- aprt-, and their antiviral properties have been characterized. In the parental Ltk- aprt- line interferon is unable to establish antiviral properties or to increase the levels of 2,5-oligo(A) synthetase, the 2,5-oligo(A)-activated endonuclease F, 2',5'-phosphodiesterase, or eIF-2 kinase. However, interferon did prevent replication of vesicular stomatitis, Mengo virus, and reovirus in some of the derivative cell lines. The effect of interferon on the levels of the enzymes of the 2,5-oligo(A) and eIF-2 kinase pathways did not correlate directly with the antiviral properties of these cell clones. Greatly increased levels of 2,5-oligo(A) synthetase occurred in one clone without activation of an antiviral state. Another clone exhibited antiviral activity without detectably increased 2,5-oligo(A) synthetase activity. Changes in the levels of endonuclease F and 2',5'-phosphodiesterase were slight in all the clones examined. Neither 2,5-oligo(A) synthetase nor eIF-2 kinase levels were altered by interferon in another clone and yet an antiviral state was established and prevented replication of vesicular stomatitis, Mengo virus, and reovirus. The results show that mechanisms other than the 2,5-oligo(A) and eIF-2 kinase pathways are likely to contribute to the antiviral effects of interferon.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

The action of recombinant bovine interferons on influenza virus replication correlates with the induction of two Mx-related proteins in bovine cells.

Recombinant bovine interferon-alpha and -gamma differ in their action against influenza virus on bovine cells. Bovine IFN-alpha severely impairs early protein synthesis and replication of influenza virus in bovine cells in contrast to bovine IFN-gamma which fails to induce an antiviral state against influenza virus. Otherwise the IFN system seems to function normally in bovine cells since both bovine IFN-alpha and -gamma induce an antiviral state against vesicular stomatitis virus. The establishment of the specific antiviral state against influenza virus correlates with the induction by bovine IFN-alpha, but not -gamma, of two cytoplasmic proteins related to the IFN-induced mouse protein Mx involved in the mechanism of resistance of mice to influenza virus infection. This study suggests that bovines possess a system for resistance to influenza virus similar to the mouse Mx system.

Animals↗
PubMed1988

Primary structure and translation of a defective interfering RNA of murine coronavirus.

An intracellular defective-interfering (DI) RNA, DIssE, of mouse hepatitis virus (MHV) obtained after serial high multiplicity passage of the virus was cloned and sequenced. DIssE RNA is composed of three noncontiguous genomic regions, representing the first 864 nucleotides of the 5' end, an internal 748 nucleotides of the polymerase gene, and 601 nucleotides from the 3' end of the parental MHV genome. The DIssE sequence contains one large continuous open reading frame. Two protein products from this open reading frame were identified both by in vitro translation and in DI-infected cells. Sequence comparison of DIssE and the corresponding parts of the parental virus genome revealed that DIssE had three base substitutions within the leader sequence and also a deletion of nine nucleotides located at the junction of the leader and the remaining genomic sequence. The 5' end of DIssE RNA was heterogeneous with respect to the number of UCUAA repeats within the leader sequence. The parental MHV genomic RNA appears to have extensive and stable secondary structures at the regions where DI RNA rearrangements occurred. These data suggest that MHV DI RNA may have been generated as a result of the discontinuous and nonprocessive manner of MHV RNA synthesis.

Amino Acid Sequence↗
PubMed1988

Reovirus type 3 synthesizes proteins in interferon-treated HeLa cells without reversing the antiviral state.

Treatment of HeLa cells with human lymphoblastoid interferon (IFN-alpha) does not inhibit reovirus type 3 protein synthesis during virus infection. In contrast, reovirus translation is blocked by treatment of L cells with mouse IFN-alpha. The (2'-5')A synthetase activity is induced in HeLa cells by IFN-alpha treatment and is activated after reovirus infection, since cell lysates from these cells synthesize in vitro (2'-5')A oligonucleotides. The IFN-induced protein kinase activity is also triggered in those lysates upon dsRNA addition. Thus, contrary to DNA-containing viruses, such as vaccinia virus or adenovirus, reovirus infection does not destroy or reverse the IFN-induced antiviral state. In support of this conclusion, superinfection with poliovirus or vesicular stomatitis virus of reovirus-infected HeLa cells treated with IFN leads only to a blockade of translation of the former viruses. These results provide a remarkable example where in the same cells doubly infected with two different viruses, the antiviral state induced by IFN-alpha is manifested by selectively inhibiting translation of one kind of virus (poliovirus or vesicular stomatitis virus) without affecting the translation of reovirus type 3. In addition, these results indicate that the resistance of reovirus translation to inhibition by IFN is different from the mechanism of resistance induced by DNA-containing viruses.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

LaCrosse virus gene expression in mammalian and mosquito cells.

LaCrosse virus infection of mammalian BHK cells is highly cytopathic, whereas that of mosquito C6/36 cells is asymptomatic and persistent. When the individual mRNAs and their genome segments are followed in parallel infections, cytopathic effects were found to correlate with the rate of synthesis, but not the accumulation, of the viral RNAs. The change from the acute to the persistent phase of the infection in C6/36 cells was found to take place at 24 hr p.i., at which time genome and N protein synthesis was severely reduced, even though mRNA levels remained high. When the persistent infection was followed for 72 days, the total amounts of genomes and their relative proportions were found to fluctuate greatly, whereas mRNA levels were either severely reduced or undetectable. DI genomes could not be detected during this time. The self-limiting nature of the mosquito cell infection appears to be due the translational control of N protein synthesis.

Animals↗
PubMed1989

Replication of the genome RNAs of defective interfering particles of vesicular stomatitis and Sendai viruses using heterologous viral proteins.

We have tested the ability of heterologous viral proteins to support the in vivo and in vitro replication of the RNA of defective interfering (DI) particles of two serotypes of VSV and of Sendai virus. In all the combinations of heterologous coinfections in vivo, DI particle replication was observed only in the coinfection with the VSV-Indiana DI particle and wild-type VSV-New Jersey. By quantitating RNA synthesis in reconstitution experiments we showed that with DI nucleocapsids isolated from infected cells, however, the soluble protein fraction from heterologous wild-type virus-infected cells could substitute in vitro to varying degrees for the homologous proteins in the elongation reaction of RNA replication and encapsidation. In these cases successful replication was confirmed by demonstrating the specific association of the heterologous N protein with the product nucleocapsid RNA. The initiation step, that is, the initial binding of the nucleocapsid protein to the leader RNA, in contrast, requires the homologous protein, since heterologous viral proteins could not support RNA replication and encapsidation from purified DI particles.

Capsid↗
PubMed1989

Comparative study on the antiviral activity of tumor necrosis factor (TNF)-alpha, lymphotoxin/TNF-beta, and IL-1 in WISH cells.

We find that pretreatment of WISH cells with tumor necrosis factor (TNF)-alpha, IL-1, and lymphotoxin/TNF-beta is capable of inducing an antiviral state in these cells, thereby protecting them from vesicular stomatitis virus cytopathic effect. Furthermore, we find that such a treatment causes a major inhibition of the synthesis of VSV proteins, as analyzed by SDS-PAGE. The 2-5A synthetase activity is also increased by treating the cells with doses of cytokines effective in antiviral protection. In this cell system, inclusion of polyclonal antibodies to IFN-beta during cytokine pretreatment abrogates the antiviral state elicited by the above cytokines, while antibodies to IFN-beta 2/IL-6 fail to abolish the cytokine-induced antiviral effects.

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Sensitive interferon assay based on immunoenzymatic quantification of viral antigen synthesis.

A sensitive enzyme immunoassay (EIA) for determining the biological activity of human interferon was developed. Green monkey kidney (Vero) cells and human embryonic lung (HEL) cells were grown in microtitre plates, treated with leukocyte interferon (IFN alpha) and infected with vesicular stomatitis virus (VSV). Cells were fixed with paraformaldehyde and permeabilized with Triton X-100. Viral antigen synthesis was measured by labelling the cells with VSV antiserum followed sequentially by protein A horseradish peroxidase conjugate and o-phenylenediamine. Interferon activity was detected as a lowering of the absorbance value from that of the virus control wells, reflecting the inhibition of virus protein synthesis by interferon. The minimum amount of interferon producing statistically significant (P less than 0.01) decrease of absorbance in Vero cells was 1-5 international units (I.U.)/ml as in the standard plaque reduction test the detection limit was 7.5 I.U./ml or more. In HEL cells the detection limit was 1 I.U./ml measured by EIA. The EIA for interferon activity is at least as sensitive as the traditional plaque reduction test. It is reproducible, easy to automatise and requires 7-10 times less cell culture materials than the plaque reduction test. We find it preferential especially when large numbers of specimens with limited volumes are to be analysed for interferon activity.

Animals↗
PubMed2004

TAP genes and immunity.

The transporter associated with antigen processing (TAP) is a member of the ATP-binding cassette transporter family that specializes in delivering cytosolic peptides to class I molecules in the endoplasmic reticulum. The TAP is a major target of genetic alteration in tumours and disruption by viral inhibitors. In some species, TAP genes have co-evolved with MHC class I molecules to deliver peptides that are customised for particular alleles. In humans, MHC class I polymorphism determines the level of tapasin-mediated association with TAP and subsequent peptide optimisation within the peptide-loading complex (PLC). MHC class I molecules that still load peptides without complexing to the TAP might be more resistant to viral interference of the PLC and less sensitive to competition for TAP by other class I allotypes.

ATP-Binding Cassette Transporters↗
PubMed2006

Viruses and sumoylation: recent highlights.

Since its discovery in 1997, SUMO (small ubiquitin-like modifier) has been implicated in a range of activities, indicating that this protein is as important in the cell as ubiquitin is. Although it can function throughout the cell, it appears to be involved more in nuclear functions. The growing list of substrates that are covalently modified by SUMO includes many viral proteins; SUMO appears to facilitate viral infection of cells, making it a possible target for antiviral therapies. It therefore is important to understand how viruses manipulate the cellular sumoylation system and how sumoylation affects viral functions.

Animals↗
PubMed2006

Viral risk factor for seizures: pathobiology of dynorphin in herpes simplex viral (HSV-1) seizures in an animal model.

Up to 89% of patients with herpes simplex virus type-1 (HSV-1) encephalitis can have seizures. Possibly, viruses are environmental triggers for seizures in genetically vulnerable individuals. Inherited dynorphin promoter polymorphisms are associated with temporal lobe epilepsy and febrile seizures in man. In animals, the dynorphin system in the hippocampus regulates excitability. The hypothesis that reduced dynorphin expression in dentate gyrus of hippocampus due to HSV-1 infection leads to epileptic responses was tested in a rat model of HSV-1 encephalitis using EEG recording, histopathological and neuropharmacologic probes. HSV-1 infection causes loss of dynorphin A-like immunoreactivity in hippocampus, an effect independent of direct viral interference and cell loss. A kappa opioid receptor agonist U50488 effectively blocks ictal activity, linking absence of dynorphin to propensity for epileptic activity. These findings show a vulnerability of hippocampal dynorphin during infection, suggesting a neurochemical basis for seizures that may be generalizable to other encephalitic viruses.

Action Potentials↗