Nucleotide sequences of herpes simplex virus type 1 (HSV-1) affecting virus entry, cell fusion, and production of glycoprotein gb (VP7).
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Biomedical subjects
Publications and source records attributed to N DeLuca.
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Herpes simplex virus type 1 is photosensitized by treatment with fluorescein isothiocyante (FITC). The inactivation of FITC-treated virions upon subsequent exposure to light is inhibited by the presence of sodium azide, suggesting the involvement of singlet oxygen in the process. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that treatment with FITC plus light induces crosslinks in viral envelope glycoproteins. Treatment of virions with high concentrations of FITC (50 micrograms/ml) plus light causes a reduction in the adsorption of the virus to monolayers of human embryonic lung cells. For lower concentrations of FITC (10 micrograms/ml) plus light, treated virions adsorb to the host cells, but remain sensitive to light until entry occurs. The loss of light sensitivity coincides with the development of resistance to antibodies. These results are most consistent with a mechanism of entry for herpes simplex virus involving fusion of the viral membrane with the plasma membrane of the host cell.
A spin-labeled virucidal agent was synthesized, purified, and tested for its activity against the enveloped bacterial virus phi6 and herpes simplex virus. This compound, designated BPN, inactivated greater than 99% of phi6 and herpes simplex virus in vitro at concentrations as low as 0.1 mM. Detailed studies were carried out on the mechanism of inactivation of phi6 by BPN. These studies revealed that treatment of phi6 by BPN specifically removes a single envelope protein that is considered to be responsible for adsorption of the virus to the host cell. Related experiments with the phi6 host, Pseudomonas phaseolicola strain HB10Y, showed that this organism is insensitive to the effects of BPN. The basis for the differential sensitivity of phi6 to BPN, in comparison to the host cell, was investigated by electron spin resonance techniques. It was found that, for phi6, HB10Y, and their extracted phospholipids, BPN is localized in the hydrocarbon zones of the membrane bilayer. However, in the case of phi6, the rotational mobility of BPN is much reduced in comparison to that in HB10Y and the phospholipid preparations. Furthermore, an Arrhenius plot of rotational correlation time (tau(c)) showed a marked discontinuity in slope at 31 degrees C in the case of phi6, but not for the other samples studied. This suggests a strong interaction between the phi6 envelope proteins and the lipid domains in which BPN is localized. Calculations based on the known lipid and protein composition of phi6 indicate that there is an absence of "free-lipid" pools in the viral envelope. It is suggested that BPN localizes in free-lipid pools of cell membranes, where its presence is of little or no consequence, but that in phi6 the BPN perturbs the hydrophobic interactions between phospholipids and proteins in the envelope.
Bacteriophage Psp231a infects Pseudomonas phaseolicola, strain HB10Y, which is the host cell for the enveloped bacteriophage phi 6. This paper describes the biophysical characteristics of Psp231a and the physical properties of its nucleic acid. In electron micrographs the virion appears as an icosahedral structure, approximately 55 nm in diameter, with a short tail. The virion density is 1.48 g/cm3 in CsCl, and the sedimentation coefficient is approximately 407S. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of 12 polypeptides ranging in molecular weight from 5,000 to 117,000. The nucleic acid of Psp231a is linear, double-stranded DNA of molecular weight 28 X 10(6). Its density in CsCl is 1.716 g/cm3, and its sedimentation coefficient in 3 M CsCl is 20.0S, corresponding to an S020,W of 34S.
The antihypertensive efficacy and tolerability of a calcium antagonist drug, diltiazem (60 mg q.i.d. per os), was compared with that of metoprolol (100 mg b.i.d. pr os) in a crossover, double-blind randomized trial in 20 patients with mild or moderate essential hypertension. Blood pressure and heart rate were assessed at rest and during bicycle exercise before and after four-week periods of treatment. Both metoprolol and diltiazem reduced significantly systolic and diastolic blood pressure, while heart rate decreased only after metoprolol therapy. The reduction in blood pressure and the percentage of patients who responded favorably were similar with the two drugs. Furthermore, the overall levels of blood pressure during exercise were significantly reduced by both treatments, while only metoprolol was able to reduce the maximum increase in systolic blood pressure and heart rate induced by exercise. These results suggest that the use of diltiazem may be appropriate to the treatment of patients with mild or moderate essential hypertension.