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

1951 ◽  
Vol 94 (4) ◽  
pp. 291-304 ◽  
Author(s):  
Oscar C. Liu ◽  
Werner Henle
Keyword(s):  
Chick Embryo ◽  
Influenza A ◽  
Allantoic Fluid ◽  
Growth Cycle ◽  
Influenza B Virus ◽  
Influenza B ◽  
In Series ◽  
The Difference ◽  
The Individual ◽  
Time Required

The combined passage of influenza A and B viruses in series, as reported by Sugg and Magill, has been confirmed. When the mixed passage materials were not too highly diluted both agents could be traced through 10 transfers. Growth curve experiments revealed that both agents developed independently, as measured by hemagglutination-inhibition tests in the presence of specific immune sera against one or the other type. However, the hemagglutinin titers of the 2 viruses in the mixed series were always substantially lower than those recorded when the strains were used individually as seed in the same concentrations as were employed in the mixed series. Assay of the infectivity titers of the individual strains in the presence of appropriate immune sera led to the demonstration that the time required for the growth cycle of influenza B virus varied with the dose of seed virus. With undiluted infected allantoic fluid as seed only 4 to 5 hours elapsed before new generations of virus were liberated. With increasing 10-fold dilution of the seed the constant period became increasingly longer until it stabilized at 8 to 10 hours. This finding offers an explanation for the seeming discrepancy between the observations on interference between the 2 viruses and the difference reported previously in the extent of their growth periods, on the one hand, and the fact that the 2 agents could be carried simultaneously in series through numerous passages in the chick embryo.

scholarly journals QUALITATIVE DIFFERENCES IN THE ANTIGENIC COMPOSITION OF INFLUENZA A VIRUS STRAINS

1944 ◽  
Vol 79 (6) ◽  
pp. 633-647 ◽  
Author(s):  
William F. Friedewald
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Serum Antibody ◽  
Allantoic Fluid ◽  
Influenza B Virus ◽  
Influenza B ◽  
Red Cell ◽  
Homologous Virus ◽  
Cell Adsorption ◽  
Virus Strains

A study of the PR8, Christie, Talmey, W.S., and swine strains of influenza A virus by means of antibody absorption tests revealed the following findings: 1. Serum antibody could be specifically absorbed with allantoic fluid containing influenza virus or, more effectively, with concentrated suspensions of virus obtained from allantoic fluid by high-speed centrifugation or by the red cell adsorption and elution technique. Normal allantoic fluid, or the centrifugalized sediment therefrom, failed to absorb antibodies. Influenza B virus (Lee) caused no detectable absorption of antibody from antisera directed against influenza A virus strains, but it specifically absorbed antibody from Lee antisera. 2. The neutralizing, agglutination-inhibiting, and complement-fixing anti-bodies in ferret antisera were completely absorbed only by the homologous virus strain, even though 2 absorptions were carried out with large amounts of heterologous virus strains. 3. PR8 virus appeared to have the broadest range of specific antigenic components for it completely absorbed the heterologous antibodies in Christie and W.S. antisera and left only those antibodies which reacted with the respective homologous strains. The other virus strains (Christie, Talmey, W.S., swine) were more specific in the absorption of heterologous antibodies and completely removed only those antibodies which reacted with the absorbing virus. 4. The absorption tests revealed a higher degree of specificity and individuality of the virus strains than the various cross reactions previously reported. The strain specificity of PR8 virus was equally manifest in absorption tests with ferret sera and with human sera following vaccination. 5. The amount of homologous antibody remaining in a PR8 ferret serum after absorption with PR8 virus, obtained by the red cell adsorption and elution method, varied inversely as the concentration of virus used for absorption. A given concentration of virus, however, absorbed a greater percentage of neutralizing antibodies than either agglutination-inhibiting or complement-fixing antibodies.

scholarly journals Comparative Outcomes of Adults Hospitalized With Seasonal Influenza A or B Virus Infection: Application of the 7-Category Ordinal Scale

2019 ◽  
Vol 6 (3) ◽  
Author(s):  
Yeming Wang ◽  
Guohui Fan ◽  
Peter Horby ◽  
Fredrick Hayden ◽  
Qian Li ◽  
...  
Keyword(s):  
Virus Infection ◽  
Clinical Improvement ◽  
Influenza A ◽  
Cox Model ◽  
Normal Activity ◽  
Ordinal Scale ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
The Difference

Abstract Background The objective of this study was to investigate the difference in disease severity between influenza A and B among hospitalized adults using a novel ordinal scale and existing clinical outcome end points. Methods A prospective, observational study was conducted over the 2016–2018 influenza seasons in a central hospital. The primary outcome was the rate of clinical improvement, defined as a decline of 2 categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death), or hospital discharge up to day 28. Results In total, 574 eligible patients were enrolled, including 369 (64.3%) influenza A cases and 205 (35.7%) influenza B cases. The proportion of patients with a worse ordinal scale at admission was higher in influenza A than influenza B (P = .0005). Clinical improvement up to 28 days occurred in 82.4% of patients with influenza A and 90.7% of patients with influenza B (P = .0067). The Cox model indicated that influenza B patients had a higher clinical improvement probability than influenza A cases (adjusted hazard ratio [HR], 1.266; 95% confidence interval [CI], 1.019–1.573; P = .0335). A similar pattern was observed in weaning oxygen supplement (adjusted HR, 1.285; 95% CI, 1.030–1.603; P = .0261). In-hospital mortality for influenza A was marginally higher than influenza B (11.4% vs 6.8%; P = .0782). Conclusions Our findings indicated that hospitalized patients with influenza A were more ill and had delayed clinical improvement compared with those with influenza B virus infection.

scholarly journals EFFECT OF SODIUM MONOFLUOROACETATE ON THE MULTIPLICATION OF INFLUENZA VIRUSES, MUMPS VIRUS, AND PNEUMONIA VIRUS OF MICE (PVM)

1952 ◽  
Vol 96 (6) ◽  
pp. 531-548 ◽  
Author(s):  
William J. Mogabgab ◽  
Frank L. Horsfall
Keyword(s):  
Chick Embryo ◽  
Influenza A ◽  
Virus Titer ◽  
Mumps Virus ◽  
Influenza Viruses ◽  
Mouse Lung ◽  
Influenza B Virus ◽  
Influenza B ◽  
Chick Embryos ◽  
And Control

Sodium fluoroacetate, given after virus inoculation in doses of 3 to 4 mg. per kg. in mice or 2 mg. in chick embryos, caused only a slight delay in the multiplication of the PR8 strain of influenza A virus in the mouse lung and of PR8 or the Lee strain of influenza B virus in the allantoic sac. The quantities of the compound used were sufficient to cause approximately 10 to 20 per cent mortality in mice and 100 per cent in chick embryos. The use of small virus inocula did not markedly increase the effect of sodium fluoroacetate on the multiplication of PR8 or Lee in the chick embryo and maximal titers were obtained in all cases. In contrast to the findings in the chick embryo, sodium fluoroacetate caused a definite delay in the multiplication of Lee virus in the mouse lung but did not affect the final virus titer. Sodium fluoroacetate in like amounts caused only a minimal delay in the multiplication of pneumonia virus of mice (PVM) in the mouse lung or of mumps virus in the chick embryo. With both PVM and mumps virus, maximal titers were obtained almost simultaneously in fluoroacetate and control animals. When three daily injections of the compound were given to mice infected previously with PVM, a definite diminution in the virus titer was demonstrable. However, pretreatment with three daily injections of the compound caused no alteration in the capacity of mice to support the multiplication of PVM. From the results of these experiments, it appears that the cellular metabolic processes blocked by sodium fluoroacetate are not essential for the multiplication of influenza viruses, mumps virus, or pneumonia virus of mice (PVM).

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

1949 ◽  
Vol 90 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Werner Henle
Keyword(s):  
Chick Embryo ◽  
Influenza A ◽  
Allantoic Fluid ◽  
Active Virus ◽  
B Virus ◽  
The Difference ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Allantoic Cavity ◽  
Partial Success

Upon injection of active influenza A or B virus into the allantoic cavity of the developing chick embryo, an average of only 70 per cent of the agent was adsorbed onto the tissue, as measured by the difference between the quantity of virus injected and that found free in the allantoic fluid of the injected eggs during the constant period. The degree of adsorption was similar, regardless of whether 109 or 102 ID50 of active virus was injected. Attempts to demonstrate the adsorbed virus in suspensions of the infected tissue met with partial success only in that not more than 1 to 5 per cent of the amount calculated to be adsorbed was actually found. All efforts to increase the yield of virus have failed. These results led to the suggestion that the seed virus, which participates in the propagation, becomes altered in such a way that it no longer may be demonstrated by infectivity titrations, whereas the active virus found represents superficially adsorbed virus, which does not multiply.

scholarly journals COMPARISONS OF INFLUENZA VIRUS STRAINS FROM THREE EPIDEMICS

1947 ◽  
Vol 86 (5) ◽  
pp. 367-381 ◽  
Author(s):  
George K. Hirst
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Strain Differences ◽  
Significant Degree ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
The Difference ◽  
Virus Strains ◽  
Better Than

Some of the peculiarities of strains of influenza A and B virus from two epidemics have been described. The influenza B virus of 1945–46, when compared with influenza A virus, proved to be much more difficult to isolate from human sources by any known means. Its adaptation to the chick embryo (by any route) or to mice was much slower than that of A virus. It did not keep nearly as well on storage at –72°C. either in throat garglings or as passage material. Its adaptation to amniotic growth was usually much better than to allantoic growth even after repeated allantoic passages. It failed to show primary evidence of occurring in the O form, although many of the secondary O characteristics were present and persisted. Its titer in throat washings was not demonstrably high as compared with certain strains of A virus, which were demonstrated in garglings at dilutions of 10–5 and 10–6. The antigenic patterns of influenza A strains from two epidemics were compared. No antigenic differences of significant degree were found among the strains of either epidemic and the difference between the strains of the two epidemics was very slight. A similar study was made of the influenza B strains of the epidemic of 1945–46. This also showed complete lack of significant strain differences. The implications of these findings for influenza prophylaxis are discussed.

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

1953 ◽  
Vol 97 (6) ◽  
pp. 889-902 ◽  
Author(s):  
Oscar C. Liu ◽  
Werner Henle
Keyword(s):  
Influenza A ◽  
High Titer ◽  
Influenza B Virus ◽  
Influenza B ◽  
Safe Procedure ◽  
Equal Distribution ◽  
End Point ◽  
The Individual ◽  
Host Virus Interactions ◽  
Virus Interactions

Equal mixtures of influenza A (PR8) and B (Lee) viruses, based on predetermined ID50 values of the individual preparations, were titrated in closely spaced steps near the 50 per cent infectivity end-point. Typing of the hemagglutinins found in the allantoic fluids after incubation of the eggs for 72 hours showed an approximately equal distribution between types A and B, when less than 2 ID50 of the mixed seed had been injected. With larger inocula influenza A became dominant because it reproduces at a faster rate than the influenza B virus. While this result agreed with expectations, it was found that passage of the allantoic fluids revealing influenza A agglutinins in mixture with anti-A serum, and of B agglutinins with anti-B, yielded the heterologous virus in many instances, even when only one-half of an ID50 of mixed seed had been administered in the original titration. "Negative" fluids obtained from embryos injected with as little as one-eighth of an ID50 upon passage yielded on occasion virus of one or the other type. Similar closely spaced titrations near the 50 per cent end-point of single strains (PR8) indicated that if hemagglutinins were found after incubation of 72 hours they were of high titer, as a rule. However, in some embryos hemagglutinins became detectable only between the 3rd and 4th days of incubation. In addition, negative allantoic fluids removed from embryos 72 hours after injection yielded on occasion virus on passage, yet no hemagglutinins were found in some of these eggs after an additional incubation period of 24 hours, or a total of 96 hours. None of the possible explanations for these various observations, which have been discussed in detail, is completely satisfactory. However, the data indicate that in infectivity titrations the ID50 end-point obtained at 72 hours, or even after 96 hours, does not reflect the total amount of virus present in the material titrated. The data also denote that separation of variants, or mutants or "genetic recombinants" by the limiting dilution technic, although possible, does not represent an absolutely safe procedure.

scholarly journals Influenza B Virus BM2 Protein Is a Crucial Component for Incorporation of Viral Ribonucleoprotein Complex into Virions during Virus Assembly

2004 ◽  
Vol 78 (20) ◽  
pp. 11007-11015 ◽  
Author(s):  
Masaki Imai ◽  
Shinji Watanabe ◽  
Ai Ninomiya ◽  
Masatsugu Obuchi ◽  
Takato Odagiri
Keyword(s):  
Influenza A ◽  
Reverse Genetics ◽  
Virus Assembly ◽  
Growth Cycle ◽  
Host Cells ◽  
Influenza B Virus ◽  
Influenza B ◽  
Ribonucleoprotein Complex ◽  
B Virus ◽  
Knockout Virus

ABSTRACT Influenza B virus contains four integral membrane proteins in its envelope. Of these, BM2 has recently been found to have ion channel activity and is considered to be a functional counterpart to influenza A virus M2, but the role of BM2 in the life cycle of influenza B virus remains unclear. In an effort to explore its function, a number of BM2 mutant viruses were generated by using a reverse genetics technique. The BM2ΔATG mutant virus synthesized BM2 at markedly lower levels but exhibited similar growth to wild-type (wt) virus. In contrast, the BM2 knockout virus, which did not produce BM2, did not grow substantially but was able to grow normally when BM2 was supplemented in trans by host cells expressing BM2. These results indicate that BM2 is a required component for the production of infectious viruses. In the one-step growth cycle, the BM2 knockout virus produced progeny viruses lacking viral ribonucleoprotein complex (vRNP). The inhibited incorporation of vRNP was regained by trans-supplementation of BM2. An immunofluorescence study of virus-infected cells revealed that distribution of hemagglutinin, nucleoprotein, and matrix (M1) protein of the BM2 knockout virus at the apical membrane did not differ from that of wt virus, whereas the sucrose gradient flotation assay revealed that the membrane association of M1 was greatly affected in the absence of BM2, resulting in a decrease of vRNP in membrane fractions. These results strongly suggest that BM2 functions to capture the M1-vRNP complex at the virion budding site during virus assembly.

scholarly journals THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION

1957 ◽  
Vol 106 (6) ◽  
pp. 851-862 ◽  
Author(s):  
Edwin D. Kilbourne ◽  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Allantoic Fluid ◽  
Influenza B Virus ◽  
Influenza B ◽  
Viral Particles ◽  
B Virus ◽  
Secondary Result ◽  
Final Yield ◽  
Experimental Viral Infection

The administration of cortisone to chicken embryos infected with influenza B virus results in (a) an initial inhibition of viral synthesis and (b) an eventual increase in the final yield of virus attained. Increased yields of virus are attained regardless of the number of viral particles in the infecting inoculum or the proportion of particles which are infective. Changes in the distribution ratios of allantoic fluid and intramembrane virus are effected by cortisone only as the secondary result of reduction in viral synthesis. The manifest effect of cortisone on influenza A virus increase is inhibitory unless inocula containing relatively high proportions of inactive viral particles are used.

scholarly journals The memberane Piece Technique for in Vitro Infectivity Titrations of Influenza Virus

1957 ◽  
Vol 55 (3) ◽  
pp. 434-456 ◽  
Author(s):  
N. B. Finter ◽  
P. Armitage
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Technical Assistance ◽  
Allantoic Fluid ◽  
Test Tube ◽  
Influenza B Virus ◽  
Influenza B ◽  
Experimental Conditions ◽  
Set Up

1. The membrane piece technique for in vitro titrations of the infectivity of influenza virus is described. Rectangles of shell, about 8 × 25 mm., with the chorio-allantoic membrane still attached (membrane pieces) are cut from thirteenth-day fertile eggs. One piece in a test-tube with glucose-buffered salt solution forms an individual assay unit. Five or more tubes are inoculated with each virus dilution. After incubation at 37° C. for 72 hr., with agitation for the first 24 hr. the fluid in each tube is tested for haemagglutinins. From the results at each dilution, an estimate of the 50% membrane piece (MP50) infectivity titre is obtained.2. Six hundred assay units, with pieces cut from twenty eggs, can be set up by two workers in 1 hr. and used for titration of between three and twenty-four individual virus preparations, depending on the reliability desired for the 50% end-point estimates.3. With the D.S.P. and PR 8 strains of influenza A virus, the MP50 titres parallel the EID50 titres from egg titrations, but are eight times and twenty times lower, respectively. The MP50: EID50 ratio is the same for various preparations of the same strain, including standard allantoic fluid and chorio-allantoic membrane virus, incomplete virus, and inactivated (heated) allantoic fluid virus. Preliminary experiments with Lee influenza B virus show that slightly different experimental conditions are required, and the MP50 titres are about fifty times less than the EID50 titres.4. Consistent results have been obtained on titration of samples of the same virus preparation on a number of occasions over a period of several months.5. A large number of membrane pieces can be used to test each virus dilution, and sampling variations in the MP50 estimates thus made quite small. Statistical data on the reliability of a 50 % titration result, and on the minimum significant differences between two end-points, are given for different values of n, the number of membrane pieces used to test each virus dilution, and of d, the log dilution step.We are grateful to Mr J. Collins for invaluable technical assistance, and also to Miss I. Allen for help with the computations.

scholarly journals INTERFERENCE BETWEEN THE INFLUENZA VIRUSES

1944 ◽  
Vol 79 (4) ◽  
pp. 379-400 ◽  
Author(s):  
James E. Ziegler ◽  
George I. Lavin ◽  
Frank L. Horsfall
Keyword(s):  
Chick Embryo ◽  
Ultraviolet Radiation ◽  
Influenza A ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Interference Phenomenon ◽  
B Virus ◽  
Virus System

Influenza A or influenza B virus rendered non-infective by ultraviolet radiation was found to be capable of producing interference with the multiplication of active influenza viruses in the chick embryo. Certain temporal and quantitative relationships affecting the interference phenomenon with this host-virus system were studied. An hypothesis of the mechanism of interference between the influenza viruses is proposed and discussed.

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