scholarly journals GROWTH CHARACTERISTICS OF INFLUENZA VIRUS CONCERNING THE BINDING OF VIRUS BY HOST CELLS

1955 ◽  
Vol 102 (5) ◽  
pp. 545-554 ◽  
Author(s):  
W. Wilbur Ackermann ◽  
Nakao Ishida ◽  
H. F. Maassab
Keyword(s):  
Influenza Virus ◽  
Infectious Virus ◽  
Chorioallantoic Membrane ◽  
Receptor Site ◽  
Blocking Effect ◽  
Growth Characteristics ◽  
Host Cells ◽  
Prolonged Incubation ◽  
Active Virus ◽  
Infectious Property

Under certain conditions, influenza virus may bind to chorioallantoic membrane and the infectious property is retained upon prolonged incubation of the complex. Apparently the bound active virus is not functioning in the initiation of viral increase. The bound infectious virus may be partially removed by extensive washing. The characteristics of the washing are suggestive of a reversible equilibrium type of binding. Binding will also occur when the tissue has been pretreated with RDE or in the presence of AMPS. However, under these conditions the binding is of a lesser degree. When the tissue has been treated with RDE and AMPS is present, no stable binding occurs. In the presence of AMPS, the initiating activity is bound but cannot function in promoting viral increase. It is proposed that active virus is held by two types of binding at the same site; one type of binding is sensitive to the action of RDE; the second type is sensitive to the blocking effect of AMPS. Virus can be held to the receptor site by either type of binding or both. It is further suggested that the bound infectious virus is a result of an abortive attempt at initiating infection. The nature of the binding of infectious virus is of significance for understanding the binding of initiating activity.

scholarly journals GROWTH CHARACTERISTICS OF INFLUENZA VIRUS

1955 ◽  
Vol 102 (4) ◽  
pp. 393-402 ◽  
Author(s):  
W. Wilbur Ackermann ◽  
Hunein F. Maassab
Keyword(s):  
Influenza Virus ◽  
Latent Period ◽  
Growth Curve ◽  
Chorioallantoic Membrane ◽  
Growth Characteristics ◽  
Stages Of Development ◽  
Viral Inhibitor ◽  
Site Of Action ◽  
Two Stages

A further analysis of the growth curve obtained in vitro for influenza virus in chorioallantoic membrane has been made using the viral inhibitor p-fluorophenylalanine. It has been found that p-fluorophenylalanine is phase-specific, does not interfere with the initiation of infection but rather acts during the productive period of the infectious sequence. The site of action of this fluoroderivative has been described relative to the site of action of methoxinine. By the use of this inhibitor in combination with methoxinine, it has been possible to recognize two stages of development which were not discernible from the usual growth curve. In a multicellular culture these two reactions, A and B, occur for the most part simultaneously, during the latent and productive periods. Reaction A is inhibited by methoxinine, but not by fluorophenylalanine. It begins early in the latent period and can proceed independent of reaction B. Reaction B is inhibited by fluorophenylalanine, but not by methoxinine, and it cannot proceed unless reaction A is proceeding or has operated for some prior interval.

scholarly journals STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM

1949 ◽  
Vol 90 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Werner Henle
Keyword(s):  
Influenza Virus ◽  
Chick Embryo ◽  
Active Agent ◽  
Allantoic Fluid ◽  
Inhibitory Effect ◽  
Influenza Viruses ◽  
Host Cells ◽  
Active Virus ◽  
Homologous Virus ◽  
Host Virus Interactions

Experiments have been reported on the propagation of influenza viruses in the allantoic membrane of the developing chick embryo during the first infectious cycle. After adsorption of the seed virus onto the host cells, only a small percentage of it remains demonstrable by infectivity titrations. This amount remains constant for 4 hours in the case of infection with PR8 virus, and for 6 hours in that of infection with Lee virus. Thereafter, a sharp rise in infectivity occurs 2 to 3 hours before liberation of the new generations of active virus into the allantoic fluid can be detected. Injection of homologous virus, inactivated by ultraviolet irradiation, following infection prevents or delays the production of virus in the tissues, depending to some extent upon the number of ID50 of active virus used as inoculum. The smaller the dose, the more pronounced the inhibitory effect. With increasing delay in the injection of the inhibitor, progressively more virus is produced and liberated 6 and 9 hours after infection with PR8 and Lee virus, respectively. Thus, production of virus may be interrupted by the homologous inhibitor when given up to 3 hours after infection with PR8, and up to4½ hours after infection with Lee virus. Since no increase in infectivity can bedetected during these 3 and 4½ hour periods in the tissues, it is suggested that influenza virus propagates in at least two major stages: first, non-infectious, immature virus material is produced which, subsequently, is converted into the fully active agent. Presumably the first step can be interrupted by the homologous inhibitor, while the second cannot. Heterologous irradiated virus, injected after infection of the tissue, exerts only a slight inhibitory effect on the production of virus.

scholarly journals THE INACTIVATION OF THE VIRUS OF EPIDEMIC INFLUENZA BY SOAPS

1940 ◽  
Vol 71 (5) ◽  
pp. 661-681 ◽  
Author(s):  
C. Chester Stock ◽  
Thomas Francis
Keyword(s):  
Fatty Acids ◽  
Influenza Virus ◽  
Oleic Acid ◽  
Chloride Solution ◽  
Calcium Chloride Solution ◽  
Hydrogen Ion ◽  
Ion Concentrations ◽  
Active Virus ◽  
The Stability ◽  
Infectious Property

The capacity of certain fatty acids at pH 7.5 to inactivate the virus of epidemic influenza has been demonstrated. Most effective of these are oleic, linolic, and linolenic acids. Studies were made of such variables as pH, rate of inactivation, and ratios of reactant concentrations, using oleic acid as a prototype of the effective acids. Attempts to recover active virus from inactive mixtures by decrease in pH, dialysis, dilution, or addition of calcium chloride solution to inactivated virus have been unsuccessful. The stability of virus at different hydrogen ion concentrations has been determined. Quantitative comparisons have been made of the immunizing capacity of fully active virus and virus rendered non-infectious by treatment with oleic acid. It was found that while the infectious property of the virus is removed the immunogenic capacity is essentially unaltered. The possible mechanism by which the soaps act upon influenza virus has been discussed.

scholarly journals ON THE ROLE OF RIBONUCLEIC ACID IN ANIMAL VIRUS SYNTHESIS

1960 ◽  
Vol 111 (3) ◽  
pp. 339-349 ◽  
Author(s):  
Igor Tamm ◽  
Marjorie M. Nemes ◽  
Suydam Osterhout
Keyword(s):  
Influenza Virus ◽  
Chorioallantoic Membrane ◽  
Inhibitory Effect ◽  
Virus Multiplication ◽  
Point Of View ◽  
Host Cells ◽  
Animal Virus ◽  
Host Cell Proteins

Adenosine, but not guanosine, was capable of blocking the inhibitory effect of 5,6-dichloro-1-ß-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-C14 into RNA of uninfected host cells, but it had little effect on uptake of C14-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.

scholarly journals GROWTH CHARACTERISTICS OF INFLUENZA VIRUS. PROPERTIES OF THE INITIAL CELL-VIRUS COMPLEX

1956 ◽  
Vol 104 (4) ◽  
pp. 501-515 ◽  
Author(s):  
Nakao Ishida ◽  
W. Wilbur Ackermann
Keyword(s):  
Influenza Virus ◽  
Chorioallantoic Membrane ◽  
Inhibitory Effect ◽  
Immune Serum ◽  
Growth Characteristics ◽  
Stable Complex ◽  
Initial Reaction ◽  
Cholera Vibrio ◽  
Virus Complex

The rate has been determined at which the initial stable complex is formed between cells of the chorioallantoic membrane and the PR8 strain of type A influenza virus. Characterization of the complex revealed the following properties: (a) stability to dilution and to simple washing with buffered saline, (b) insensitivity to the action of receptor-destroying enzyme (obtained from cholera vibrio), (c) sensitivity to the inhibitory effect of anti-viral immune serum, (d) formation of the complex at low temperatures, 3°C., (e) accompanied by a loss of detectable viral infectivity from the reaction mixture, (f) stability at 3°C. but transformation at 37°C. to a state which is resistant to the inhibitory action of a specific anti-viral serum. The rate of this latter transformation has been determined. The infectious process in more than 50 per cent of the cells can be influenced by immune serum 2 hours after the completion of the initial reaction with virus.

scholarly journals THE ANTIGENIC POTENCY OF EPIDEMIC INFLUENZA VIRUS FOLLOWING INACTIVATION BY ULTRAVIOLET RADIATION

1940 ◽  
Vol 72 (6) ◽  
pp. 729-745 ◽  
Author(s):  
Jonas E. Salk ◽  
G. I. Lavin ◽  
Thomas Francis
Keyword(s):  
Tissue Culture ◽  
Influenza Virus ◽  
Ultraviolet Radiation ◽  
Culture Medium ◽  
Tissue Culture Medium ◽  
Intraperitoneal Route ◽  
Active Virus ◽  
High Concentrations

A study of the antigenic potency of influenza virus inactivated by ultraviolet radiation has been made. Virus so inactivated is still capable of functioning as an immunizing agent when given to mice by the intraperitoneal route. In high concentrations inactivated virus appears to be nearly as effective as active virus but when quantitative comparisons of the immunity induced by different dilutions are made, it is seen that a hundredfold loss in immunizing capacity occurs during inactivation. Virus in suspensions prepared from the lungs of infected mice is inactivated more rapidly than virus in tissue culture medium. A standard for the comparison of vaccines of epidemic influenza virus is proposed.

scholarly journals SOME ENERGY RELATIONS IN A HOST-VIRUS SYSTEM

1953 ◽  
Vol 97 (3) ◽  
pp. 315-322 ◽  
Author(s):  
W. Wilbur Ackermann ◽  
R. Bernal Johnson ◽  
Keyword(s):  
Influenza Virus ◽  
Chorioallantoic Membrane ◽  
Host Tissue ◽  
Endogenous Respiration ◽  
Excellent Correlation ◽  
Viral Propagation ◽  
Twofold Increase ◽  
Energy Relations ◽  
Virus System ◽  
Stimulation Of

It was found that DNP (2,4-dinitrophenol) will inhibit completely the propagation of influenza virus in chorioallantoic membrane. This reagent did not permanently alter those metabolic processes required for the synthesis of virus and at the concentrations employed demonstrated no virucidal effects. In minced preparations of chorioallantoic membrane DNP was shown to have a pronounced stimulatory effect upon ATPase (adenosinetriphosphatase). When DNP was used with intact tissues, an excellent correlation was found between the inhibition of viral propagation and the stimulation of respiration and release of phosphate. Concentrations of DNP which permitted a twofold increase in the endogenous respiration of intact membranes allowed little or no viral synthesis. It is concluded that the energy required for viral synthesis derives from the oxidative phosphorylative activity of the host tissue.

scholarly journals ON THE ROLE OF RIBONUCLEIC ACID IN ANIMAL VIRUS SYNTHESIS

1960 ◽  
Vol 111 (3) ◽  
pp. 351-368 ◽  
Author(s):  
Igor Tamm ◽  
Rostom Bablanian
Keyword(s):  
Herpes Simplex ◽  
Vaccinia Virus ◽  
Ribonucleic Acid ◽  
Chorioallantoic Membrane ◽  
Host Cells ◽  
Active Inhibitor ◽  
Herpes Simplex Viruses ◽  
Virus Particles ◽  
Highly Active

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 µg. 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.

scholarly journals Epitope specificity plays a critical role in regulating antibody-dependent cell-mediated cytotoxicity against influenza A virus

2016 ◽  
Vol 113 (42) ◽  
pp. 11931-11936 ◽  
Author(s):  
Wenqian He ◽  
Gene S. Tan ◽  
Caitlin E. Mullarkey ◽  
Amanda J. Lee ◽  
Mannie Man Wai Lam ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Critical Role ◽  
Host Cells ◽  
Viral Glycoprotein ◽  
Effector Functions ◽  
Dependent Cell

The generation of strain-specific neutralizing antibodies against influenza A virus is known to confer potent protection against homologous infections. The majority of these antibodies bind to the hemagglutinin (HA) head domain and function by blocking the receptor binding site, preventing infection of host cells. Recently, elicitation of broadly neutralizing antibodies which target the conserved HA stalk domain has become a promising “universal” influenza virus vaccine strategy. The ability of these antibodies to elicit Fc-dependent effector functions has emerged as an important mechanism through which protection is achieved in vivo. However, the way in which Fc-dependent effector functions are regulated by polyclonal influenza virus-binding antibody mixtures in vivo has never been defined. Here, we demonstrate that interactions among viral glycoprotein-binding antibodies of varying specificities regulate the magnitude of antibody-dependent cell-mediated cytotoxicity induction. We show that the mechanism responsible for this phenotype relies upon competition for binding to HA on the surface of infected cells and virus particles. Nonneutralizing antibodies were poor inducers and did not inhibit antibody-dependent cell-mediated cytotoxicity. Interestingly, anti-neuraminidase antibodies weakly induced antibody-dependent cell-mediated cytotoxicity and enhanced induction in the presence of HA stalk-binding antibodies in an additive manner. Our data demonstrate that antibody specificity plays an important role in the regulation of ADCC, and that cross-talk among antibodies of varying specificities determines the magnitude of Fc receptor-mediated effector functions.

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