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P Whitaker-Dowling

Publications and source records attributed to P Whitaker-Dowling.

28 records · Page 2Linked to original sources
PubMed1987

Regulation of cardiac myosin synthesis: studies of RNA content in cultured heart cells.

Contraction regulates the myosin content and the rate of myosin synthesis in cultured neonatal rat heart cells. To further explore the mechanism for this regulation we examined various parameters of RNA content and RNA synthesis in contacting versus noncontracting myocytes. While contraction stimulated myosin heavy chain (MHC) synthesis by 72% compared to that of KCl-arrested cells, simultaneous analyses of polysome profiles were no different under the two culture conditions. Incorporation of [3H]uridine monophosphate into cellular RNA revealed no change in the rate of total RNA or ribosomal subunits synthesis. In vitro translation of cellular RNA yielded similar incorporation of [35S]methionine into trichloroacetic acid precipitable protein. Specific transcription of the MHC gene was examined by dot-blot analysis and was unaltered by contraction. Northern blot analysis of the MHC sequences detected by a cDNA probe revealed an mRNA sequence corresponding to a molecular weight of approximately 30 S. These data suggest that RNA synthesis and RNA content are unaltered by contraction in cultured heart cells and therefore the changes in myosin synthesis may be mediated at a post-transcriptional control level.

Animals↗
PubMed1987

Interferon pretreatment enhances the sensitivity of Vero cells to Clostridium perfringens type A enterotoxin.

Treatment of Vero (African green monkey kidney) cells with interferon (IFN) before the addition of Clostridium perfringens type A enterotoxin (CPE) significantly increased the sensitivity of these cells to CPE. IFN pretreatment caused a subsequent two- to four-fold increase in CPE-induced membrane permeability alterations and also decreased the time of CPE treatment required before the onset of permeability alterations and morphologic damage. Enhancement of CPE activity was dependent on the amount of IFN added during pretreatment and on the duration of IFN pretreatment incubations. Potentiation of CPE activity was observed following pretreatment of Vero cells with natural human IFN-alpha or IFN-gamma or Roferon recombinant human IFN-alpha. However, pretreatment with mouse IFN did not affect CPE activity. IFN pretreatment did not grossly enlarge the size of the functional hole produced in plasma membranes by CPE. IFN pretreatment of Vero cells slightly increased CPE specific binding, but this effect occurred kinetically after the enhancement of CPE toxicity. These results suggest that IFN pretreatment enhances the action of CPE on IFN pretreated Vero cells by increasing the sensitivity of these cells to the action of CPE rather than by increasing CPE specific binding or by directly activating the CPE molecule. Additional studies are required to further clarify the mechanism by which IFN sensitized Vero cells to CPE.

Animals↗
PubMed1987

The mechanism of the antiviral effect of interferon differs in two strains of a rabbit kidney cell line.

Two variant strains of a rabbit kidney cell line, RK-13, differ markedly in their interferon (IFN)-mediated antiviral mechanism. Both strains are permissive for the growth of vesicular stomatitis (VSV) and vaccinia viruses. Following treatment with 100 U/ml of rabbit IFN, both cell strains restrict VSV yield about a 1000-fold; vaccinia is not inhibited by IFN in either cell strain. However, vaccinia is able to rescue VSV from the inhibitory effects of IFN in one strain (RK-13), but not in the other strain of cells (RK-13-37). Investigation of the mechanism of this phenomenon reveals that VSV growth is blocked at different levels in the two cell strains. In the strain in which vaccinia can rescue VSV from the effects of IFN (RK-13), the major IFN-mediated restriction of VSV growth is at the level of protein synthesis; in the other strain in which vaccinia is unable to rescue VSV (RK-13-37), IFN restricts VSV at earlier steps, including penetration and primary transcription. The two cell strains provide useful models for studying the multifaceted nature of IFN-mediated antiviral effects.

Animals↗
PubMed1986

Vaccinia-mediated rescue of encephalomyocarditis virus from the inhibitory effects of interferon.

Coinfection of mouse L cells with vaccinia virus rescues encephalomyocarditis virus (EMC) from the inhibitory effect of interferon (IFN). The vaccinia-mediated rescue of EMC growth increases the yield of EMC as much as 1000-fold and is optimum when vaccinia is used at a multiplicity of infection of 1. This rescue correlates with a vaccinia-dependent stimulation of EMC gene expression. Evidence is presented to indicate that the rescue by vaccinia does not involve a block of the 2'-5'A synthetase pathway. However, the vaccinia rescue function is correlated with a vaccinia-mediated inhibition of the IFN-induced protein kinase.

2',5'-Oligoadenylate Synthetase↗
PubMed1986

Dominance of temperature-sensitive phenotypes. I. Studies of the mechanism of inhibition of the growth of wild-type vesicular stomatitis virus.

It has been reported previously that temperature-sensitive (ts) mutants of vesicular stomatitis virus (VSV) with an RNA- phenotype interfere with the growth of wild-type (wt)-VSV at both the permissive (34 degrees) and nonpermissive (39.5 degrees) temperatures (J. S. Youngner and D. O. Quagliana (1976) J. Virol. 19, 102-107). Investigation of the mechanism of this interference has revealed the following information. In double infection with RNA- ts mutants and wt-VSV, the cumulative synthesis of viral RNA is inhibited. By varying the relative multiplicities of the two viruses, it was observed that the level of RNA synthesis reflects the level of interference with wt-VSV growth. Although viral RNA synthesis was severely compromised in double infections, this inhibition was not at the level of primary transcription or the translation of primary transcripts. Rather, secondary transcription and genome RNA replication were drastically reduced. Sequential infection with wt-VSV and the ts mutants revealed that there is an early point in the replication cycle of wt-VSV (1 to 2 hr) after which the ts mutants can no longer interfere with the growth of wt-VSV. Ultraviolet irradiation of ts G 41, a mutant belonging to complementation group IV, was used to determine the target size of the interference function. The calculated value for the target size was very close to the target size of the N gene. Additional experiments showed that RNA+ ts mutants representing complementation groups III and V also were able to interfere with the growth of wt-VSV.

Genes, Dominant↗
PubMed1984

Characterization of a specific kinase inhibitory factor produced by vaccinia virus which inhibits the interferon-induced protein kinase.

When mouse L cells are infected by vaccinia virus, a specific kinase inhibitory factor is produced which inhibits the interferon-induced, double-stranded RNA-dependent protein kinase (P. Whitaker-Dowling and J. S. Youngner (1983) Virology 131, 128-136). This inhibitory factor appears early in vaccinia infection (90 min) and its production requires protein synthesis. It inhibits the phosphorylation of the alpha subunit of protein synthesis initiation factor eIF-2 and it is active in mixed extracts of IFN-treated cells and vaccinia-infected cells. The vaccinia-mediated inhibition of the IFN-induced protein kinase is not due to a specific phosphatase or a specific protease and can be reversed by the addition of excess double-stranded RNA. Evidence is presented which suggests that the specific kinase inhibitory factor interacts in a stoichiometric manner with the double-stranded RNA which is required for the activation of the interferon-induced protein kinase.

Animals↗
PubMed1983

Vaccinia rescue of VSV from interferon-induced resistance: reversal of translation block and inhibition of protein kinase activity.

Coinfection with vaccinia virus rescues vesicular stomatitis virus (VSV) from the inhibitory effects of interferon (IFN) in mouse L cells. While vaccinia infection does not significantly affect VSV RNA synthesis, coinfection with vaccinia dramatically increases VSV protein synthesis in IFN-treated cells. Evidence is provided that vaccinia inhibits the activity of the IFN-induced dsRNA-dependent protein kinase.

Animals↗
PubMed1983

Superinfection exclusion by vesicular stomatitis virus.

The infection of baby hamster kidney (BHK21) cells by the Indiana strain of vesicular stomatitis virus (VSV) causes a rapid loss of the ability of the cells to be superinfected by VSV virions or defective-interfering particles. This exclusion phenomenon is at the level of virus penetration and requires viral gene expression and a functional VSV transmembrane glycoprotein G. Infection with the New Jersey serotype of VSV also inhibits the uptake of the Indiana serotype. However, infection of BHK21 cells with either encephalomyocarditis, Newcastle disease, or influenza A viruses does not inhibit superinfection by VSV.

Animals↗