scholarly journals NEUTRALIZATION TESTS WITH SERA OF CONVALESCENT OR IMMUNIZED ANIMALS AND THE VIRUSES OF SWINE AND HUMAN INFLUENZA

1936 ◽  
Vol 63 (5) ◽  
pp. 645-653 ◽  
Author(s):  
Thomas Francis ◽  
Richard E. Shope

Human and swine influenza viruses were regularly neutralized by their homologous immune sera. However, the sera of animals convalescent from infection with either the swine or human influenza virus possessed little, if any, neutralizing capacity for the heterologous virus. Hyperimmunization of animals against swine influenza virus tended to increase the neutralizing capacity of their sera for human influenza virus, but in an inconstant fashion, whereas repeated inoculations with human influenza virus frequently resulted in sera with strong neutralizing activities against swine influenza virus. These observations serve to emphasize both the immunological distinctiveness and the interrelationships of swine and human influenza viruses.

1937 ◽  
Vol 66 (2) ◽  
pp. 151-168 ◽  
Author(s):  
Richard E. Shope

Swine recovered from infection with either swine influenza or swine influenza virus alone are usually not only immune but refractory to human influenza infection. Swine recovered from infection with a mixture of human influenza virus and H. influenzae suis are usually immune to swine influenza while those recovered from infection with human influenza virus alone are usually not immune to swine influenza. The possible mechanisms involved in the cross-immunity between the influenza viruses are discussed.


2015 ◽  
Vol 89 (22) ◽  
pp. 11275-11283 ◽  
Author(s):  
Heather M. Machkovech ◽  
Trevor Bedford ◽  
Marc A. Suchard ◽  
Jesse D. Bloom

ABSTRACTNumerous experimental studies have demonstrated that CD8+T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+T cells. Here we use a novel computational approach to test for selection in CD8+T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint.IMPORTANCEThere is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8+T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal models and are associated with decreased symptoms in humans, no studies have proven with statistical significance that influenza virus evolves under positive selection to escape T cells. Here we use comparisons of human and swine influenza viruses to rigorously demonstrate that human influenza virus evolves under pressure to fix mutations in the nucleoprotein that promote escape from T cells. We further show that viruses with these mutations have a selective advantage since they are preferentially located on the “trunk” of the phylogenetic tree. Overall, our results show that CD8+T cells targeting nucleoprotein play an important role in shaping influenza virus evolution.


1935 ◽  
Vol 62 (4) ◽  
pp. 561-572 ◽  
Author(s):  
Richard E. Shope

The experiments confirm the earlier observation of Andrewes, Laidlaw and Smith that the swine influenza virus is pathogenic for white mice when administered intranasally. Two field strains of the swine influenza virus were found to differ in their initial pathogenicity for mice. One strain was apparently fully pathogenic even in its 1st mouse passage while the other required 2 or 3 mouse passages to acquire full virulence for this species. Both strains, however, were initially infectious for mice, without the necessity of intervening ferret passages. There is no evidence that bacteria play any significant rôle in the mouse disease though essential in that of swine, and fatal pneumonias can be produced in mice by pure virus infections. Mice surviving the virus disease are immune to reinfection for at least a month. In mice the disease is not contagious though it is notably so in swine. The virus, while regularly producing fatal pneumonias when administered intranasally to mice, appears to be completely innocuous when given subcutaneously or intraperitoneally. Prolonged serial passage of the virus in mice does not influence its infectivity or virulence for swine or ferrets. It is a stable virus so far as its infectivity is concerned, and can be transferred at will from any one of its three known susceptible hosts to any other. In discussing these facts the stability of the swine influenza virus has been contrasted with the apparent instability of freshly isolated strains of the human influenza virus. Though the mouse is an un-natural host for the virus it is, nevertheless, useful for the study of those aspects of swine influenza which have to do with the virus only.


1936 ◽  
Vol 63 (5) ◽  
pp. 655-668 ◽  
Author(s):  
Thomas Francis ◽  
T. P. Magill

The results of mouse protection tests with 136 human sera and a strain of human influenza virus are described. After the 1st year of life, the sera of approximately half the individuals tested contained sufficient antibody to furnish complete protection to mice. A much higher percentage of the sera obtained from individuals recently convalescent from influenza exerted a completely protective effect. On the other hand, certain sera protected only partially under the conditions of the tests. The results have been compared with those obtained by Shope in tests done with the same sera against swine influenza virus. The possible epidemiological significance of the results is discussed.


2010 ◽  
Vol 41 (5) ◽  
pp. 74 ◽  
Author(s):  
Núria Busquets ◽  
Joaquim Segalés ◽  
Lorena Córdoba ◽  
Tufaria Mussá ◽  
Elisa Crisci ◽  
...  

1936 ◽  
Vol 64 (5) ◽  
pp. 791-801 ◽  
Author(s):  
Richard E. Shope ◽  
Thomas Francis

Swine inoculated intranasally with human influenza virus alone develop an ill defined, mild, and usually afebrile illness of short duration. At postmortem the anterior lobes of the lungs of such animals contain scant, scattered areas of lobular atelectasis. Transmission of the virus for 5 serial passages through two groups of swine failed noticeably to enhance its pathogenicity for this species. The disease produced in swine by infection with human influenza virus alone is indistinguishable clinically and pathologically from that caused by infection with swine influenza virus alone. Transmission of human influenza virus from swine to swine by contact succeeded in only one of four attempts. Swine inoculated intranasally with a mixture of human influenza virus and H. influenzae suis usually develop a febrile, depressing illness similar to mild swine influenza. The pneumonia encountered in such animals at autopsy is similar to but less extensive than that seen in swine influenza. In some animals H. influenzae suis fails to become established and the disease then seen is identical with that caused by human influenza virus alone. The human influenza virus recovered after 5 serial transfers in swine was immunologically the same as that with which the experiments were begun.


1943 ◽  
Vol 77 (1) ◽  
pp. 7-20 ◽  
Author(s):  
Frederik B. Bang

The synergistic effect of Hemophilus influenzae suis and swine influenza virus in the pig can be reproduced by the inoculation of these agents on the chorioallantoic membrane of 9 to 10 day old chick embryos. Two strains of human influenza virus that were studied failed to substitute for the swine virus in the synergistic reaction. No loss of synergistic effect was noted when the swine influenza virus was put through 11 chick embryo passages. Recently isolated and old stock strains of Hemophilus were equally able to enhance the effect of the virus. Heat-killed cultures of H. influenzae suis can be substituted for the bacterial component of the reaction. Infection of the embryo with swine influenza virus predisposes to infection with H. influenzae suis. The combination of H. influenzae suis and swine influenza virus causes a selective destruction of the embryo lungs, not produced by the individual components. This pneumonia exhibits the essential features of the natural disease.


1939 ◽  
Vol 69 (6) ◽  
pp. 847-856 ◽  
Author(s):  
Richard E. Shope

1. Cross-neutralization tests with sera from swine recovered from infection with swine influenza indicated the serological identity of 7 strains of swine influenza virus obtained from different sources. 2. Cross-neutralization tests with sera from rabbits, immunized to swine influenza virus, exposed serological differences among the same 7 swine influenza virus strains. Two strains appeared to be serologically similar and were characterized by the ability to produce effective homologous virus-neutralizing sera which were, however, poor or ineffective against the heterologous virus strains. Two other strains were also serologically similar but produced antibodies effective not only against themselves, but against all heterologous strains as well. The remaining 3 strains were intermediate in their ability to produce heterologous virus-neutralizing antibodies. 3. The human influenza viruses included, especially strains WS and Oakham, were most effectively differentiated serologically from the swine influenza viruses by rabbit antisera. 4. The suggestion is advanced that swine antisera express the antigenic composition of the swine influenza viruses, while rabbit antisera reflect either their antigenic arrangement or the arrangement of the components responsible for their mouse pathogenicity. On this interpretation the 7 strains of swine influenza virus studied would be considered to have similar antigenic compositions but differing antigenic structures. 5. The serological differences among strains of the swine influenza virus, detectible by rabbit antisera, are probably of no practical significance so far as the natural disease, swine influenza, is concerned.


2013 ◽  
Vol 9 (2) ◽  
pp. e1003176 ◽  
Author(s):  
Ben M. Hause ◽  
Mariette Ducatez ◽  
Emily A. Collin ◽  
Zhiguang Ran ◽  
Runxia Liu ◽  
...  

2019 ◽  
Vol 85 (10) ◽  
Author(s):  
Joanna A. Pulit-Penaloza ◽  
Jessica A. Belser ◽  
Terrence M. Tumpey ◽  
Taronna R. Maines

ABSTRACT The relative importance of influenza virus transmission via aerosols is not fully understood, but experimental data suggest that aerosol transmission may represent a critical mode of influenza virus spread among humans. Decades ago, prototypical laboratory strains of influenza were shown to persist in aerosols; however, there is a paucity of data available covering currently circulating influenza viruses, which differ significantly from their predecessors. In this study, we evaluated the longevity of influenza viruses in aerosols generated in the laboratory. We selected a panel of H1 viruses that exhibit diverse transmission profiles in the ferret model, including four human isolates of swine origin (referred to as variant) and a seasonal strain. By measuring the ratio of viral RNA to infectious virus maintained in aerosols over time, we show that influenza viruses known to transmit efficiently through the air display enhanced stability in an aerosol state for prolonged periods compared to those viruses that do not transmit as efficiently. We then assessed whether H1 influenza virus was still capable of infecting and causing disease in ferrets after being aged in suspended aerosols. Ferrets exposed to very low levels of influenza virus (≤17 PFU) in aerosols aged for 15 or 30 min became infected, with five of six ferrets shedding virus in nasal washes at titers on par with ferrets who inhaled higher doses of unaged influenza virus. We describe here an underreported characteristic of influenza viruses, stability in aerosols, and make a direct connection to the role this characteristic plays in influenza transmission. IMPORTANCE Each time a swine influenza virus transmits to a human, it provides an opportunity for the virus to acquire adaptations needed for sustained human-to-human transmission. Here, we use aerobiology techniques to test the stability of swine-origin H1 subtype viruses in aerosols and evaluate their infectivity in ferrets. Our results show that highly transmissible influenza viruses display enhanced stability in an aerosol state compared to viruses that do not transmit as efficiently. Similar to human-adapted strains, swine-origin influenza viruses are infectious in ferrets at low doses even after prolonged suspension in the air. These data underscore the risk of airborne swine-origin influenza viruses and support the need for continued surveillance and refinement of innovative laboratory methods to investigate mammalian exposure to inhaled pathogens. Determination of the molecular markers that affect the longevity of airborne influenza viruses will improve our ability to quickly identify emerging strains that present the greatest threat to public health.


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