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Biomedical subjects

I TAMM

Publications and source records attributed to I TAMM.

At least 37 records · Page 2Linked to original sources
PubMed1961

Biochemical basis for alterations in structure and function of HeLa cells infected with Newcastle disease virus.

The ability of NDV-infected HeLa cells to synthesize DNA, protein, and RNA was investigated by measuring the incorporation of tritiated precursors into these substances at intervals after infection of cells with a virus/cell multiplicity of 500:1. A significant decrease in incorporation of precursors into DNA and protein was first observed at 3(1/4) hours after infection. By 4(1/2) hours, an 80 to 90 per cent decrease had occurred, and by 5(1/4) hours, incorporation of precursors into DNA and protein was almost completely inhibited. Incorporation of precursor into RNA decreased gradually following infection; by the 10th hour, a 40 per cent decrease had occurred. These results, integrated with earlier observations on biological aspects of infection, suggest the following causal relationships among events in NDV-infected cells: (a) The cessation of virus production is probably caused by inhibition of protein or RNA synthesis, and is not due to inhibition of DNA synthesis or to interferon. (b) The production of infective virus does not per se interfere with the ability of an infected cell to divide, nor is inhibition of mitosis caused by either inhibition of DNA synthesis or development of marked degenerative changes in infected cells. Inhibition of mitosis may be the result of inhibition of protein or RNA synthesis, (c) Marked cell damage could have been caused by inhibition of protein, DNA, or RNA synthesis, (d) Interference by NDV with the multiplication of influenza virus was probably due to the inhibitory effects of NDV on cellular biosynthetic activities.

Animals↗
PubMed1961

Relationship between structure of benzimidazole derivatives and selective virus inhibitory activity. Inhibition of poliovirus multiplication and cytopathic effects by 2-(alpha-hydroxybenzyl)-benzimidazole, and its 5-chloroderivative.

The virus inhibitory activity and selectivity of certain benzimidazole, benzotriazole, and naphthimidazole derivatives were determined with influenza B and polio type 2 viruses. Among the sixty-five compounds examined, several were highly active inhibitors of influenza B virus multiplication in the chorioallantoic membrane in vitro. The following compounds, listed in order of increasing inhibitory activity, were more than 100 times as active as benzimidazole: 5-(4'-toluenesulfonamido)-benzimidazole, 5-hydroxybenzotriazole-4-carboxy-alpha-naphthylamide, 4,5,6-trichlorobenzotriazole, 5-(3',4'-dichlorobenzenesulfonamido)-benzimidazole, 5-(3',4'-dichlorobenzenesulfonamido) - 1 - (3'',4'' - dichlorobenzenesulfonyl)-benzimidazole, 4-(p-chlorophenylazo)-5-hydroxybenzotriazole, and 4,5,6,7-tetrachlorobenzotriazole. However, none showed high selectivity. Of the sixty-five compounds studied with influenza virus, twenty-five were also examined with poliovirus type 2 in monkey kidney cells in vitro. Included in this group were five of the seven most active inhibitors of influenza virus, listed above. All five were more than 100 times as active in inhibiting poliovirus multiplication as the reference compound. In addition to these, two other compounds were highly active: 2-(alpha-hydroxybenzyl)-benzimidazole (HBB), and 2-(alpha-hydroxybenzyl)-5-chlorobenzimidazole, with relative inhibitory activities of 78 and 130, respectively. These two compounds, and the much less active 5,6-dichloro derivative of HBB, were the only ones which showed no, or only slight, toxic effects on cells at concentrations sufficient to cause considerable inhibition of poliovirus multiplication. Furthermore, HBB and the 5-chloro derivative were the only compounds which caused significant inhibition of the cytopathic effects of poliovirus. HBB, and its 5-chloro and 5,6-dichloro derivatives had no effect on the multiplication of influenza B virus in the chorioallantoic membrane. In addition, HBB failed to inhibit influenza B virus multiplication and cytopathic effects in monkey kidney cells. Inhibition of poliovirus-induced cell damage by HBB was characterized by the following features: the curves relating reduction in virus yield or cytopathic effects to concentration of the compound followed an approximately parallel course; somewhat higher concentrations were required to inhibit virus-induced cell damage than to reduce virus yield. HBB suppressed viral cytopathic effects for a period of time which varied directly with the concentration of compound, and inversely with the size of virus inoculum. The development of virus-induced cell damage in treated cultures on prolonged incubation was not due to inactivation of HBB. The inhibitory effect of HBB on virus-induced cell damage was reversible by removal of the compound. HBB inhibited viral cytopathic effects when given during the exponential increase phase in virus multiplication. Inhibition of virus-induced cell damage by HBB was demonstrated by photomicrographs. HBB did not inactivate the infectivity of poliovirus type 2.

Benzimidazoles↗
PubMed1961

Spectrum and characteristics of the virus inhibitory action of 2-(alpha-hydroxybenzyl)-benzimidazole.

2-(alpha-Hydroxybenzyl)-benzimidazole (HBB) inhibited the cytopathic effects of the following enteroviruses: polio 1 to 3; Coxsackie A9; Coxsackie B 1 to 6; and ECHO virus types 1 to 9, 11 to 21, and 24 to 27. The following enteroviruses were not inhibited: Coxsackie A types 7, 11, 13, 16, and 18; and ECHO types 22, 23, and 28. Other HBB-insusceptible viruses were: arbor B and C, reo 1 to 3; adeno 2 to 4; influenza B; para-influenza 2 and 3; mumps; herpes simplex, and vaccinia. HBB had no inactivating effect on viral infectivity, but rather inhibited some intracellular step in the reproductive cycle of susceptible viruses. With all viruses examined, inhibition of viral cytopathic effects appeared to be due to inhibition of virus multiplication. Virus inhibition by HBB was demonstrable in monkey kidney, HeLa, and ERK cells. HBB-susceptible viruses varied quantitatively in their susceptibility to the compound, and different strains of the same virus also exhibited varying susceptibility. No relationship was found between attenuation of polioviruses and their susceptibility to the compound. After passage of HBB-susceptible enteroviruses in the presence of the compound, virus populations with lowered susceptibility to HBB were obtained. At virus inhibitory concentrations, HBB did not affect the morphology of cells, nor the following cellular metabolic activities: oxygen uptake; glucose utilization; lactic acid production; and incorporation of adenosine into RNA, and of alanine into proteins. The rates of multiplication of HeLa and ERK. cells were not significantly altered by HBB at virus inhibitory concentrations.

Adenosine↗
PubMed1961

Enumeration of cell-infecting particles of Newcastle disease virus by the fluorescent antibody technique.

A procedure has been developed for the determination of the concentration of infective Newcastle disease virus (NDV) based on the enumeration of singly infected and distributed HeLa cells which are visualized by staining with fluorescent antibody. Infective virus assayed by the fluorescent cell-counting procedure is expressed in terms of cell-infecting units (CIU). Adsorption of NDV to HeLa cell monolayers reached a plateau 1 to 1.5 hours after inoculation of coverslip cultures, and 12 per cent of the infective particles inoculated failed to adsorb. The half-life of NDV in protein-free Eagle's medium at 37 degrees C. was 2.1 hours. There was a linear relationship between virus concentration and the number of infected cells. The coefficient of variation of the mean of replicate determinations of infective NDV was 8.2 per cent. The distribution of single infected HeLa cells in the monolayer corresponded to the Poisson distribution. With NDV the cell-infecting unit (CIU) determined in HeLa cells is equivalent to the plaque-forming unit in chick embryo cells and the egg infective dose. In experiments on the mechanism of dissemination of NDV in monolayer cultures of HeLa cells, NDV was found to spread from cell to cell through the extracellular milieu.

Animals↗
PubMed1961

Effect of multiplicity of infection on Newcastle disease virus-HeLa cell interaction.

The effects of a hundred-fold difference in virus/cell multiplicity on the interaction of Newcastle disease virus (NDV) with HeLa cells were studied, and various phases of the virus reproductive cycle were related to cellular consequences of infection. At both multiplicities used all cells were infected. The following events occurred 1 to 2 hours earlier in cells which were inoculated with the higher multiplicity: (a) first appearance of newly made virus antigen, and the amount present at any time during the period of rapid increase; (b) onset and time course of production of infective virus; (c) development by infected cells of hemadsorbing ability; (d) onset and time course of inhibition of mitosis; and (e) onset and time course of marked cell damage. Double infection of HeLa cells with NDV and NWS was demonstrated by the fluorescent antibody technique, and was used to show that the establishment of interference against NWS was also dependent upon the multiplicity of NDV. In cells inoculated at each multiplicity, newly made virus antigen appeared at the same time as the first infective virus particles. Infective virus rapidly reached a peak, and then declined. Viral antigen continued to increase for several hours after the decline in infective virus had begun. Thus, only a small fraction of the virus antigen produced was incorporated into new infective particles. The maximal yield of such particles was only 6 to 11 per HeLa cell. Over 95 per cent of new virus was cell-associated, but could be neutralized by treatment with antiserum before disruption of cells. Mitosis occurred in cells which had produced and released infective NDV. Progressive inhibition of mitotic activity in infected cells was correlated with continued production of viral antigen. Marked cytopathic changes developed after mitotic activity had decreased to low levels. The mechanism by which NDV inhibits mitosis in HeLa cells is discussed.

Animals↗
PubMed1960

Studies of two kinds of virus particles which comprise influenza A2 virus strains. II. Reactivity with virus inhibitors in normal sera.

Inhibitors present in normal human and animal sera prevented hemagglutination by and neutralized infectivity of inhibitor-sensitive influenza A2 virus. Starch zone electrophoresis of sera indicated that the same serum components possess both hemagglutination-inhibiting and neutralizing activities. The greatest amount of inhibitory activity was found in normal horse serum, and the inhibitory activity increased with heating or treatment with concentrated solutions of urea. The inhibitory activities on human, ferret, and rabbit sera were markedly reduced but not completely eliminated by V. cholerae filtrate and purified neuraminidase. The inhibitory activity of horse serum was only moderately reduced by these agents. The nature of the horse serum inhibitor and the differences in the interactions of inhibitor-sensitive and insensitive influenza A2 virus particles and pre-1957 influenza viruses with receptors have been discussed.

Animals↗
PubMed1960

Studies of two kinds of virus particles which comprise influenza A2 virus strains. III. Morphological characteristics: independence to morphological and functional traits.

Seven strains of influenza A2 virus were serially passed in the chick embryo, and morphological characteristics of the passages were examined in the electron microscope. With serial passage there was a change from a prominently filamentous appearance in early passages to an almost entirely spherical appearance in later passages. The number of passages required for the conversion to spherical morphology varied with different strains. The filament-sphere variation was found to be independent of the properties which differentiate "+" and "-" influenza A2 virus particles, and both highly filamentous and spherical populations of "+" and of "-" virus particles were obtained. The usefulness of these pairs of independent markers for genetic studies is discussed.

Animals↗
PubMed1960

On the role of ribonucleic acid in animal virus synthesis. I. Studies with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

Adenosine, but not guanosine, was capable of blocking the inhibitory effect of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) on influenza virus multiplication in the chorioallantoic membrane in vitro. At virus inhibitory concentrations DRB caused marked inhibition in uptake of adenosine-8-C(14) into RNA of uninfected host cells, but it had little effect on uptake of C(14)-L-alanine into host cell proteins or on cellular oxygen consumption. The activity of DRB in inhibiting multiplication of the DNA-containing adenovirus was similar to its inhibitory activity on multiplication of the RNA-containing influenza virus. These and earlier results are discussed from the point of view of the important role of RNA in the reproduction of DNA-containing viruses.

Adenosine↗
PubMed1960

On the role of ribonucleic acid in animal virus synthesis. II. Studies with ribonuclease.

Ribonuclease is a highly active inhibitor of vaccinia virus multiplication in vitro in the chorioallantoic membrane removed from embryonated chicken eggs. It is also a highly active inhibitor of pock formation by vaccinia and herpes simplex viruses on the chorioallantoic membrane in vivo. Marked inhibitory effects were obtained with 12.5 microg. of RNase. However, complete inhibition was not obtained with several hundred micrograms of the enzyme. RNase caused no inactivation of the infectivity of vaccinia virus particles but it had a marked inhibitory effect on multiplication of this virus when administered many hours after infection of host cells had occurred. RNase also failed to inactivate the infectivity of herpes simplex virus particles. The results obtained indicate that ribonucleic acid is necessary for the multiplication of two DNA-containing viruses; i.e., vaccinia and herpes simplex.

Animals↗