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At least 145 records · Page 8Linked to original sources
PubMed1984

Phenotypic characterization and physical mapping of a temperature-sensitive mutant of Autographa californica nuclear polyhedrosis virus defective in DNA synthesis.

A ts mutant of Autographa californica nuclear polyhedrosis virus (AcMNPV), ts8, was shown to be defective in viral DNA synthesis at the nonpermissive temperature. Ts8-infected cells synthesized only early viral polypeptides at the nonpermissive temperature, and in contrast to wild-type (WT)-infected cells, showed no inhibition of host cell protein synthesis. The effect of the mutation on viral DNA synthesis was not immediately reversed after shifting infected cells down from the nonpermissive temperature to the permissive temperature; rather, a delay of several hours occurred before viral DNA synthesis was detected. The rate of accumulation of viral DNA in ts8-infected cells failed to increase after a shift from the permissive temperature to the nonpermissive temperature. This indicated that the ts8 mutation was involved in the synthesis of proteins required for viral DNA synthesis. The mutation was mapped by marker rescue to the region lying between 60.1 and 62.0% of the AcMNPV physical map.

Animals↗
PubMed1975

Differential induction of tumour antigens by transformation-defective virus mutants.

Normal rat kidney cells infected by a variety of transformation-defective temperature-sensitive avian leukosis sarcoma virus mutants were tested for the expression of transformation characteristics at permissive and restrictive temperature. Morphology, growth behaviour and agglutinability by concanavalin A corresponded fully to the phenotype of the infected cells: at permissive temperature the cells resembled wild type virus transformed cells, whereas when grown under restrictive conditions they became virtually indistinguishable from normal cells. The quantitative expression of allo- or xenogeneic cell surface antigens was not significantly affected by the phenotype of the cells. Two out of the five tested mutants induced tumour antigens in the expected temperature-dependent manner, whereas the other three mutants were able to induce tumour-specific cell surface antigens even in the revertant cells cultured at the restrictive temperature. These findings extend previous results about tumour antigen induction in mutant-infected cells of the natural host, the chicken embryo fibroblasts. The value of transformation-defective tumour antigen-positive mutants for vaccination purposes will be discussed.

Alpharetrovirus↗
PubMed1986

Subclinical infections in mice resulting from the modulation of a lethal dose of Semliki Forest virus with defective interfering viruses: neurochemical abnormalities in the central nervous system.

The lethal encephalitis caused in mice by Semliki Forest virus (SFV) is modulated to a subclinical infection by administration of defective interfering SFV, although virus still multiplies both in the central nervous system (CNS) and systemically. Here we report that such infections result in unique and selective changes in the normal levels of CNS neurotransmitters some of which persist after infectious virus can no longer be detected. This represents a previously undocumented category of infection which may have a bearing on the aetiology of those human neurological and neuropsychiatric diseases to which viruses are believed to contribute.

Animals↗
PubMed1991

Immune response in pigs to Aujeszky's disease viruses defective in glycoprotein g1 or gX.

Two Aujeszky's disease virus glycoprotein genes, gX and g1, have been used to produce deletion mutants which have then been developed into vaccines. These deletions then allow differentiation between pigs infected with wild type virus and those given the vaccine. It is not clear whether the glycoproteins encoded for by these genes are needed to induce a full protective immune response, in which case deletion mutants would suffer from lack of potency. To test this, commercially available Aujeszky's virus vaccines which lacked either gX or g1 were compared and isogenic constructs were made which differed only in the absence or presence of gX and, or, g1. These constructs and vaccines were used to vaccinate the natural host of Aujeszky's disease, the pig, and potency was measured using challenge with wild type virus. In all cases vaccines which lacked g1 performed significantly less well than those in which g1 was present, whereas deletions of gX had no significant effect on vaccine performance.

Animals↗
PubMed1975

Mapping RNase T1-resistant oligonucleotides of avian tumor virus RNAs: sarcoma-specific oligonucleotides are near the poly(A) end and oligonucleotides common to sarcoma and transformation-defective viruses are at the poly(A) end.

The large RNase T1-resistant oligonucleotides of the nondefective (nd) Rous sarcoma virus (RSV): Prague RSV of subgroup B (PR-B), PR-C and B77 of subgroup C; of their transformation-defective (td0 deletion mutants: td PR-B, td PR-C, and td B77; and of replication-defective (rd) RSV(-) were completely or partially mapped on the 30 to 40S viral RNAs. The location of a given oligonucleotide relative to the poly(A) terminus of the viral RNAs was directly deduced from the smallest size of the poly(A)-tagged RNA fragment from which it could be isolated. Identification of distinct oligonucleotides was based on their location in the electrophoretic/chromatographic fingerprint pattern and on analysis of their RNase A-resistant fragments. The following results were obtained. (i) The number of large oligonucleotides per poly(A)-tagged ffagment increased with increasing size of the fragment. This implies that the genetic map is linear and that a given RNase T1-resistant oligonucleotides has, relative to the poly(A) end, the same location on all 30 to 40S RNA subunits of a given 60 to 70S viral RNA complex, (ii) Three sarcoma-specific oligonucleotides were identified in the RNAs of Pr-B, PR-C and B77 by comparison with the RNAs of the corresponding td viruses...

Avian Sarcoma Viruses↗
PubMed1983

Herpes simplex virus defective genomes: structure of HSV-1 ANG defective DNA of class II and encoded polypeptides.

Sequence organization and origin of HSV-1 strain Angelotti (ANG) class II defective DNA (HSV-1 ANG dDNA1) were examined in detail by establishing physical maps and by molecular cloning. dDNA1 consists of concatemers of tandem repeat units in which sequences from the UL region spanning map coordinates 0.37 to 0.415 of standard HSV ANG DNA are covalently linked to TRS/IRS sequences. The size of the repeat unit was determined to be about 8.9 kilobase pairs (kb), comprising sequences of 7.3 kb from UL and 1.6 kb from TRS/IRS regions. UL sequences were delineated by restriction enzyme sites KpnI N-P and EcoRI F-M, and were colinear with the corresponding sequences of the standard (wild-type) virus genome. Expression of dDNA1 was studied in African green monkey kidney cells and in Xenopus laevis oocytes. A major polypeptide of approx. mol. wt. 135 000 (135K) was overproduced, suggesting that this protein was encoded by dDNA1. By several parameters, e.g. size, immune cross-reactivity, and affinity for native and denatured DNA, the 135K polypeptide was identified as the major HSV DNA-binding protein. It was further shown that the repeat unit contains part of the DNA polymerase gene as demonstrated by its ability to rescue some mutations in this gene.

Base Sequence↗
PubMed1997

Immunologic havoc induced by the 60 kD Gag protein of the MAIDS defective virus.

The mechanisms responsible for development of profound immunodeficiency and extensive lymphoproliferation that characterize infection of different species with retroviruses are only partially understood. In mice, it has been shown the activities of an unusual Gag protein are necessary and sufficient to induce these abnormalities in a syndrome designated mouse AIDS (MAIDS). Current studies suggest that complex, antigen-driven interactions between T cells and B cells result in polyclonal activation of both types of lymphocytes, aberrant cytokine production and late lymphomas.

Animals↗
PubMed2000

Infectivity of Moloney murine leukemia virus defective in late assembly events is restored by late assembly domains of other retroviruses.

The p12 region of the Moloney murine leukemia virus (M-MuLV) Gag protein contains a PPPY motif important for efficient virion assembly and release. To probe the function of the PPPY motif, a series of insertions of homologous and heterologous motifs from other retroviruses were introduced at various positions in a mutant gag gene lacking the PPPY motif. The assembly defects of the PPPY deletion mutant could be rescued by insertion of a wild-type PPPY motif and flanking sequences at several ectopic positions in the Gag protein. The late assembly domain (L-domain) of Rous sarcoma virus (RSV) or human immunodeficiency virus type 1 (HIV-1) could also fully or partially restore M-MuLV assembly when introduced into matrix, p12, or nucleocapsid domains of the mutant M-MuLV Gag protein lacking the PPPY motif. Strikingly, mutant viruses carrying the RSV or the HIV-1 L-domain at the original location of the deleted PPPY motif were replication competent in rodent cells. These data suggest that the PPPY motif of M-MuLV acts in a partially position-independent manner and is functionally interchangeable with L-domains of other retroviruses. Electron microscopy studies revealed that deletion of the entire p12 region resulted in the formation of tube-like rather than spherical particles. Remarkably, the PPPY deletion mutant formed chain structures composed of multiple viral particles linked on the cell surface. Many of the mutants with heterologous L-domains released virions with wild-type morphology.

Amino Acid Motifs↗
PubMed2003

Replication of Carnation Italian ringspot virus defective interfering RNA in Saccharomyces cerevisiae.

Two plasmids from which the sequences coding for the 36- and 95-kDa proteins of Carnation Italian ringspot virus (CIRV) could be transcribed in vivo in the yeast Saccharomyces cerevisiae under the control of the ADH1 promoter and terminator were constructed. The two proteins, which constitute the viral replicase, were correctly translated and integrated into membranes of the yeast cells. An additional plasmid was introduced in yeasts expressing the CIRV replicase, from which a defective interfering (DI) RNA (DI-7 RNA) could be transcribed under the control of the GAL1 promoter and terminated by the Tobacco ringspot virus satellite ribozyme, which cleaved 19 nucleotides downstream of the 3' end of DI RNA. The DI-7 RNA transcripts were amplified by the viral replicase as demonstrated by the restoration of the authentic 3' end, the requirement of a specific cis-acting signal at this terminus, the preferential accumulation of molecules with the authentic 5' terminus (AGAAA), the synthesis of head-to-tail dimers, the presence of negative strands, and the incorporation of 5-bromo-UTP. Additionally, transformation with a dimeric construct of DI-7 RNA led to the synthesis of monomers, mimicking the activity of the viral replicase in plant cells.

Defective Viruses↗
PubMed1982

Host range mutants of vesicular stomatitis virus defective in in vitro RNA methylation.

The viral RNA polymerase of detergent-treated vesicular stomatitis virus normally synthesizes viral mRNAs in vitro that are both guanylylated and methylated to give 5'-terminal 7mGpppAm caps. We have characterized a virus host range mutant, hr 1, that is totally defective in vitro in the methylation of mRNA, although full-length polyadenylylated mRNAs with 5' termini of the form GpppA are synthesized in normal yields. A second mutant, hr 8, is partially defective in methylation and synthesizes mRNAs in vitro with primarily GpppA and some GpppAm 5' termini. When used for in vitro translation, the unmethylated hr 1 mutant mRNA shows, as expected, reduced synthesis of viral proteins. These data provide direct evidence that the vesicular stomatitis virus-associated methyltransferase activities are virus encoded.

Cell-Free System↗
PubMed1980

Oligonucleotide sequence analyses indicate that vesicular stomatitis virus large defective interfering virus particle RNA is made by internal deletion: evidence for similar transcription polyadenylation signals for the synthesis of all vesicular stomatitis virus mRNA species.

RNase T(1) oligonucleotide fingerprint analyses of three vesicular stomatitis virus Indiana serotype small defective interfering (DI) particle RNA species indicate that they only have oligonucleotides derived from the 5' region of the viral genome. These studies also indicate that these three DI RNAs have partial L gene sequences as well as two 5' viral oligonucleotides (59 and 70) that are not transcribed into L (or other) mRNA species (J. P. Clewley and D. H. L. Bishop, J. Virol. 30:116-123, 1979). Analyses of the large DI RNA (LT DI) reveal a different origin. The LT DI RNA has oligonucleotides derived from both the 3' end of the genome (including all the large oligonucleotides identified for N, NS, M, and G genes), in addition to at least one of the 5'-proximal L gene oligonucleotides (47), as well as all seven oligonucleotides (3, 38, 42, 43, 44B, 59, and 70) that are not protected from nuclease digestion after the formation of mRNA-viral RNA duplexes (Clewley and Bishop). It appears therefore that the genesis of LT RNA involves a deletion of internal L gene sequences from the viral RNA. Oligonucleotide sequence analyses have been undertaken on several of the vesicular stomatitis viral RNA oligonucleotides, including all seven (3, 38, 42, 43, 44B, 59, and 70) that are not transcribed into mRNA. The analyses confirm that oligonucleotides 59 [3'...GAACACCAAAAAUAAAAAAUA(G)...5'] and 70 [3'...GACCAAAACACCA(G)...5'] are at the 5'-end region of the viral genome. Oligonucleotide 38 [3'...GAAAUUCAUACUUUUUU(U)(G)...5'] may represent the termination signal for L mRNA synthesis (R. A. Lazzarini, personal communication). Oligonucleotide 43 [3'...GUAUACUUUUUUU(G)...5'] corresponds to the sequence shown to be the N gene mRNA polyadenylation signal (D. J. McGeoch, Cell 17:673-681, 1979). The other three oligonucleotides share a common feature with oligonucleotides 43 and 38, viz., a stretch of 6 or 7 U residues preceded by an AUAC sequence. Thus the sequence of oligonucleotide 3 is 3'...GAAUUAAUAUAAAAUUAAAAAUUAAAAAUACUUUUUU(U)(G)...5', whereas that of oligonucleotide 42 is 3'...GAUACUUUUUUUCAU(U)(G)...5', and that of oligonucleotide 44B is 3'...G(U)AUACUUUUUU(G)...5'. These sequence analyses suggest a common polyadenylation signal for the synthesis of all vesicular stomatitis virus mRNA species, i.e., the sequence (3')...AUACUUUUUU(U)...(5').

Animals↗
PubMed1984

Characterization of the infections of permissive and nonpermissive cells by host range mutants of vesicular stomatitis virus defective in RNA methylation.

Two host range mutants of VSV, hr 1 and hr 8, which, unlike the wild-type virus, have a mRNA methylation defect and direct the in vitro synthesis of full-length capped but unmethylated viral mRNAs have been described previously (S.M. Horikami and S.A. Moyer, 1982, Proc. Natl, Acad. Sci. USA 79, 7694-7698). It is shown that the in vivo nonpermissive infection of HEp-2 cells by either of these two mutants is characterized by the reduced synthesis of full-length mRNAs at levels characteristic of primary transcription and the total lack of synthesis of genome-length RNA. The VSV mRNAs synthesized by either mutant in HEp-2 cells are not translated either in vivo or in vitro in mRNA-dependent rabbit reticulocyte lysates. Subsequent isolation and analysis of the mRNAs from infected HEp-2 cells has shown that the 5' termini of the messages contain a cap structure which is guanylylated, but unmethylated (GpppA), a finding that might account for the lack of translatability. Hence these mutants are unable to properly methylate mRNAs whether they are synthesized in vitro or in vivo within nonpermissively infected cells. It is also shown that unlike hr 1, the undermethylation of mRNA synthesized by hr 8 is partially reversible by the addition of high levels of AdoMet in vitro. It is interesting to note, therefore, that permissive baby hamster kidney (BHK) cells have a 10-fold higher level of endogenous AdoMet than the nonpermissive HEp-2 cells. Unlike singly infected cells, the coinfection of HEp-2 cells with either hr mutant and a poxvirus yields a permissive infection for these two host range mutants. Analysis of the VSV mRNAs produced in vivo under the conditions of rescue reveals the presence of fully methylated caps (7mGppp(m)Am), suggesting that poxvirus may rescue the mutants by converting the VSV mRNAs to a translationally active form due to methylation by the cytoplasmic poxvirus mRNA methyltransferase enzymes. Both mutants are, however, able to grow normally in permissive BHK cells. An analysis of the translationally active mRNAs from infected permissive cells shows the presence primarily of a 5'-monomethylated cap, 7mGpppA. Finally, we have examined the nonpermissive infections of two other host range mutants of VSV (hr 5 and hr 7). Unlike mutants hr 1 and hr 8 described above, these two mutants synthesize mRNA in HEp-2 cells which is translated both in vivo and in vitro.

Animals↗
PubMed1979

Selective isolation of mutants of vesicular stomatitis virus defective in production of the viral glycoprotein.

We describe a procedure that enriches for temperature-sensitive (ts) mutants of vesicular stomatitis virus (VSV), Indiana serotype, which are conditionally defective in the biosynthesis of the viral glycoprotein. The selection procedure depends on the rescue of pseudotypes of known ts VSV mutants in complementation group V (corresponding to the viral G protein) by growth at 39.5 degrees C in cells preinfected with the avian retrovirus Rous-associated virus 1 (RAV-1). Seventeen nonleaky ts mutants were isolated from mutagenized stocks of VSV. Eight induced no synthesis of VSV proteins at the nonpermissive temperature and hence were not studied further. Four mutants belonged to complementation group V and resembled other ts (V) mutations in their thermolability, production at 39.5 degrees C of noninfectious particles specifically deficient in VSV G protein, synthesis at 39.5 degrees C of normal levels of viral RNA and protein, and ability to be rescued at 39.5 degrees C by preinfection of cells by avian retroviruses. Five new ts mutants were, unexpectedly, in complementation group IV, the putative structural gene for the viral nucleocapsid (N) protein. At 39.5 degrees C these mutants also induced formation of noninfectious particles relatively deficient in G protein, and production of infectious virus at 39.5 degrees C was also enhanced by preinfection with RAV-1, although not to the same extent as in the case of the group V mutants. We believe that the primary effect of the ts mutation is a reduced synthesis of the nucleocapsid and thus an inhibition of synthesis of all viral proteins; apparently, the accumulation of G protein at the surface is not sufficient to envelope all the viral nucleocapsids, or the mutation in the nucleocapsid prevents proper assembly of G into virions. The selection procedure, based on pseudotype formation with glycoproteins encoded by an unrelated virus, has potential use for the isolation of new glycoprotein mutants of diverse groups of enveloped viruses.

Animals↗
PubMed1995

Analysis of ALV-based packaging cell lines for production of contaminant defective viruses.

We have previously described avian leukosis virus-based packaging cell lines that express gag, pol, and env proteins from two transcomplementing genomes and produce helper-free stocks of retroviral vectors with different host ranges. In this report, we demonstrated that (i) despite the deletion of the psi packaging sequence, the packaging-defective transcomplementing retroviral transcripts were packaged into virions at a level that could reach 2.3% of a wild-type virus packaging level and (ii) despite deletion of the 3' LTR, these genomes were transferred along with the vector to target cells. As these genomes were also bearing a selectable gene, titers of the resulting contaminant particles could be estimated, depending on the cell line to be between 0 and 6 infectious particles/ml of supernatant.

Animals↗