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Biomedical subjects

B Oberg

Publications and source records attributed to B Oberg.

15 recordsLinked to original sources
PubMed1979

The effect of pyrophosphate analogues on influenza virus RNA polymerase and influenza virus multiplication.

Analogues of pyrophosphate have been tested as inhibitors of influenza virus-RNA polymerase activity in cell-free assays. The most active compound, phosphonoformic acid (PFA), reduced the polymerase activity to 50 per cent at a concentration of 20 muM. The inhibition was dependent on the type of divalent cation present in the assay. PFA at a concentration of 400 muM also inhibited the influenza virus plaque formation by 90 per cent.

DNA-Directed RNA Polymerases↗
PubMed1979

Phosphonoformate inhibits reverse transcriptase.

The new antiviral substance phosphonoformate (PFA) has been tested in a cell-free system for its effect on reverse transcriptases from an avian retrovirus (avian myeloblastosis virus, AMV) and from mammalian retroviruses (Rauscher leukaemia virus, RMuLV; bovine leukaemia virus; baboon endogenous virus; simian sarcoma virus; visna virus). The observed inhibitory effect of PFA has been compared with that of a structurally related substance, phosphonoacetate (PAA). Phosphonoformate, at a concentration of 100 microM, reduced the activities of all the above mentioned polymerases by 90% when (rA)n.(dT)10 was used as a template/primer. The dose-response curves for AMV and RMuLV polymerases primed with (rA)n.(dT)10 showed PFA to be a 1000-fold more active than PAA; the RMuLV polymerase activity was reduced to 50% after incubation with 0.7 microM-PFA and 0.7 mM-PAA, respectively. There was no difference in PFA inhibition of virus-associated and purified reverse transcriptase activity. Results with various synthetic templates showed that both the RNA- and the DNA-dependent polymerase activities of reverse transcriptase were inhibited by PFA. The endogenous polymerase activity of AMV was inhibited to 50% at 100 microM-PFA, while PAA had no effect. The PFA inhibition was dependent on whether Mg2+ or Mn2+ was used as divalent cation in the assay. Phosphonoformate arrested DNA synthesis immediately after being added to the assay system. The mechanism of inhibition of the AMV polymerase was non-competitive with respect to substrate and template and the apparent inhibition constants were 16 microM and 9 microM, respectively.

Animals↗
PubMed1979

Trisodium phosphonoformate inhibits hepatitis B Dane particle DNA polymerase.

Evidence available indicates that the so-called Dane particles are the hepatitis virus. A DNA polymerase is associated with the core of these particles. The probability that this is the viral DNA polymerase offers the possibility of preventing hepatitis B multiplication by selective inhibition of this enzyme. This investigation reports that trisodium phosphonoformate (PFA) at low concentrations but not phosphonoacetate acid (PAA) inhitits Dane particle associated DNA polymerase.

Formates↗
PubMed1979

Characteristics of herpesvirus mutants resistant to phosphonoformate and phosphonoacetate.

Mutants of herpes simplex virus type 1, resistant to phosphonoformate (PFA) and phosphonoacetate (PAA), have been selected in cell culture. The PFA-resistant mutant (HSV-PFA(r)) and the PAA-resistant mutant (HSV-PAA(r)) were also resistant to PAA and PFA, respectively. This cross-resistance indicates that PFA and PAA interact at the same site. The HSV-PFA(r) had a decreased susceptibility to vidarabine, but no difference in sensitivity to idoxuridine (5-iodo-2'-deoxyuridine) was observed when compared to the wild type. The induced deoxyribonucleic acid polymerases isolated from cells infected with HSV-PFA(r) and HSV-PAA(r) were both cross-resistant to inhibition by PFA and PAA. No increased resistance to vidarabine triphosphate could be observed, but the susceptibility to inhibition by pyrophosphate was about two times lower. None of the mutants showed any increased temperature sensitivity

Antiviral Agents↗
PubMed1978

Trisodium phosphonoformate, a new antiviral compound.

Trisodium phosphonoformate selectively inhibits cell-free DNA polymerase activity induced by herpesvirus. The new inhibitor has an antiviral effect on herpes simplex virus types 1 and 2, pseudorables virus, and infectious bovine rhinotracheitis virus in cell culture. It has a good therapeutic activity against cutaneous herpes simplex virus infection in guinea pigs.

Animals↗
PubMed1978

Comparison of the therapeutic effects of five antiviral agents on cutaneous herpesvirus infection in guinea pigs.

Cutaneous herpesvirus infection of guinea pigs has been evaluated as a model for testing antiviral compounds. Six infected sites on each animal can be used independently for local treatment. The severity of the infection has been graded in a score system. The cumulative scores during infection and the time to healing can be used to determine antiviral effects. The effects of adenine arabinoside, cytosine arabinoside, iododeoxyuridine, ribavirin and phosphonoacetic acid on the cutaneous infection was compared. Phosphonoacetic acid was the only compound with a good therapeutic activity against herpesvirus infection, causing a reduction of both the cumulative score and the time to healing. Phosphonoacetic acid was skin irritating at 2 per cent, but at 1 per cent, which still had a good therapeutic activity, skin irritation was seen only occasionally.

Animals↗
PubMed1978

Reversible inhibition of cellular metabolism by ribavirin.

The broad spectrum antiviral drug ribavirin (Virazole, 1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) inhibits cellular macromolecular synthesis as well as cell division in eucaryotic cells. The concentration and time dependence have been studied. One-hour treatment with 25 muM ribavirin or 18 h with 2 muM inhibited the deoxyribonucleic acid synthesis to 50%. Higher concentrations of ribavirin were required to obtain a similar inhibition of ribonucleic acid and protein synthesis. This effect on cell metabolism and cell division can be reversed by removing the drug from the cells.

Cell Division↗
PubMed1978

Therapeutic effect of trisodium phosphonoformate on cutaneous herpesvirus infection in guinea pigs.

When applied topically, trisodium phosphonoformate (PFA) displayed activity against established cutaneous herpesvirus infections in guinea pigs similar to that exhibited by the closely related phosphonoacetic acid (PAA); however, unlike PAA, PFA was not locally skin irritating. The therapeutic benefits of topical application of PFA were clearly evident when application was delayed for 48 h after virus inoculation, at which time lesions were well developed. The therapeutic effect was dependent on the concentration of PFA and the duration of treatment. PFA exhibited significant activity against established infections when administered intraperitoneally, although it was less effective via this systemic route than when applied topically.

Animals↗
PubMed1978

Purification and characterization of an early protein (E14K) from adenovirus type 2-infected cells.

One adenovirus type 2 (Ad2) early protein, with an apparent molecular weight of 14,000 in sodium dodecyl sulfate-polyacrylamide gels (E14K), was purified to homogeneity. Purification involved fractionation of cytoplasmic extracts, precipitation at low pH, and DEAE-cellulose, phosphocellulose, and hydroxylapatite chromatography. The yield was around 12 microgram of purified protein per 10(9) HeLa cells. The two Ad2 DNA binding proteins with molecular weights of 75,000 and 45,000 (E75K and E45K) were purified by the same procedure. Tryptic peptide analyses indicated that the E14K protein is unrelated to the DNA binding proteins. The purified E14K protein has a high content of basic amino acids and a sedimentation coefficient of 5.5S in the native state, corresponding to a molecular weight of around 95,000. Pulse-chase experiments suggest that the E14K polypeptide is a primary translation product. Immunoprecipitation with a monospecific antiserum against the E14K protein revealed that it is exclusively localized in the cytoplasm of infected cells. E14K started to be synthesized at 2 hpostinfection, with a maximal rate of synthesis at 4 to 6 h postinfection. Immunoprecipitation of cell extracts from four different Ad2-transformed hamster embryo cell lines revealed that only one (Ad2HE4) of them expresses this protein. The adenovirus-simian virus 40 hybrid virus (Ad2ND1) does not express this protein, suggesting that the gene for the E14K protein is located in the part of the Ad2 genome which is deleted in this hybrid virus.

Adenoviruses, Human↗
PubMed1977

Inhibition of influenza virus ribonucleic acid polymerase by ribavirin triphosphate.

Ribavirin 5'-triphosphate (RTP), derived from the broad-spectrum antiviral compound ribavirin (Virazole), can selectively inhibit influenza virus ribonucleic acid polymerase in a cell-free assay. Ribavirin and its 5'-monophosphate have no effect on the polymerase. The inhibition is competitive with respect to adenosine 5'-triphosphate and guanosine 5'-triphosphate. RTP also inhibits ApG- and GpC-stimulated influenza virus ribonucleic acid polymerase. Since ribavirin is phosphorylated in the cell, the inhibition of influenza multiplication in the cell may also be caused by RTP.

DNA-Directed RNA Polymerases↗
PubMed1977

In vitro translation with adenovirus polyribosomes.

Polyribosomes isolated from adenovirus type 2 (Ad2)-infected HeLa cells late in productive infection can be used for translation in cell-free systems. At least eight viral polypeptides are synthesized, including the precursors to virion polypeptides VI and VII. Separation of polyribosomes by zonal rate centrifugation followed by translation in a cell-free system reveals a correlation between the sizes of the polyribosomes and the polypeptides synthesized. The cell-free extracts incorporate amino acid linearly for only 10 min and show little or no capacity to reinitiate protein synthesis. The elongation efficiency measured as the number of amino acids incorporated per ribosome in 20 min is low, ranging from 10 to 100. The maximum chain elongation rate is estimated to be 10 to 20 amino acids per min. The limited elongation has been used to assess the relative concentration of mRNA's engaged in translation.

Adenoviruses, Human↗
PubMed1976

Purification of adenovirus messenger ribonucleic acid by an aqueous polymer two-phase system.

An aqueous polymer phase system containing 6.3% (w/w) dextran and 3.5% (w/w) poly(ethylene glycol) in 10 mM phosphate buffer (pH 8.0) was developed to select RNA-DNA hybrids from unhybridized RNA. The top phase of this phase system, which contains DNA and the RNA-DNA hybrids, can be used to purify adenovirus messenger RNA both early and late in the infectious cycle. The hybrids can be melted by heat in the top phase and the messenger RNA selected by oligo(dT)cellulose chromatography whereupon the polymers and the DNA percolate and the polyadenylated messenger RNA absorb to the column. The isolated messenger RNA appears to be almost quantitatively recovered at a purity from 70 to 90% depending on the concentration of the specific messenger RNA in the starting material. Early and late viral messenger RNA were selected on the complementary strands of adenovirus DNA according to this procedure.

Adenoviruses, Human↗
PubMed1975

Identification of the in vitro translation products of adenovirus mRNA by immunoprecipitation.

Adenovirus type 2 mRNA was translated in S30 extracts from Ehrlich ascites and wheat embryo cells. The in vitro products were identified by sodium dodecyl sulfate-gel electrophoresis after immunoprecipitation with specific antisera in the presence of urea. Seven virion polypeptides could be identified by immunoprecipitation. Three of these appear to be precursors to polypeptides of the virion. mRNA isolated late in adenovirus infection was separated into three size classes by zonal sedimentation. Material sedimenting at 26S was translated into polypeptides corresponding to the largest virion polypeptides II to IV, a 22S fraction corresponding to polypeptide V, and smaller polypeptides and a 15S fraction corresponding to polypeptide IX. A significant amount of polypeptide IX was also synthesized by the 26S and 22S RNA.

Adenoviridae↗