THE INCIDENCE OF NEUTRALIZING ANTIBODIES FOR HUMAN INFLUENZA VIRUS IN THE SERUM OF HUMAN INDIVIDUALS OF DIFFERENT AGES

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.

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THE INCIDENCE OF NEUTRALIZING ANTIBODIES FOR SWINE INFLUENZA VIRUS IN THE SERA OF HUMAN BEINGS OF DIFFERENT AGES

Journal of Experimental Medicine ◽

10.1084/jem.63.5.669 ◽

1936 ◽

Vol 63 (5) ◽

pp. 669-684 ◽

Cited By ~ 90

Author(s):

Richard E. Shope

Keyword(s):

Influenza Virus ◽

Neutralizing Antibodies ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Human Beings ◽

Human Influenza ◽

Human Sera ◽

History Of ◽

Human Adults ◽

Very High

Sera from a very high proportion of the human adults and new-born infants studied neutralized swine influenza virus; sera from children below the age of 12 years seldom exerted such an effect. The results of neutralization experiments with human sera and the virus of swine influenza have been compared with the outcome of similar tests with the virus of human influenza, and it seems evident that the presence of antibodies neutralizing swine influenza virus cannot be deemed the result of repeated exposures to the current human type of virus. From the known history of swine influenza and the similarity of its etiologic virus to that obtained from man it seems likely that the virus of swine influenza is the surviving prototype of the agent primarily responsible for the great human pandemic of 1918, as Laidlaw has already suggested. The presence in human sera of antibodies neutralizing swine influenza virus is believed to indicate a previous immunizing exposure to, or infection with, an influenza virus of the 1918 type.

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THE INFECTION OF MICE WITH SWINE INFLUENZA VIRUS

Journal of Experimental Medicine ◽

10.1084/jem.62.4.561 ◽

1935 ◽

Vol 62 (4) ◽

pp. 561-572 ◽

Cited By ~ 23

Author(s):

Richard E. Shope

Keyword(s):

Influenza Virus ◽

Virus Disease ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Serial Passage ◽

Virus Infections ◽

Human Influenza ◽

Human Influenza Virus ◽

The Stability ◽

At Will

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.

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Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus

Veterinary Research ◽

10.1051/vetres/2010046 ◽

2010 ◽

Vol 41 (5) ◽

pp. 74 ◽

Cited By ~ 55

Author(s):

Núria Busquets ◽

Joaquim Segalés ◽

Lorena Córdoba ◽

Tufaria Mussá ◽

Elisa Crisci ◽

...

Keyword(s):

Influenza Virus ◽

Experimental Infection ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Pandemic H1n1 ◽

Human Influenza ◽

Human Influenza Virus

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THE SUSCEPTIBILITY OF SWINE TO THE VIRUS OF HUMAN INFLUENZA

Journal of Experimental Medicine ◽

10.1084/jem.64.5.791 ◽

1936 ◽

Vol 64 (5) ◽

pp. 791-801 ◽

Cited By ~ 25

Author(s):

Richard E. Shope ◽

Thomas Francis

Keyword(s):

Influenza Virus ◽

Short Duration ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Human Influenza ◽

Human Influenza Virus

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.

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SYNERGISTIC ACTION OF HEMOPHILUS INFLUENZAE SUIS AND THE SWINE INFLUENZA VIRUS ON THE CHICK EMBRYO

Journal of Experimental Medicine ◽

10.1084/jem.77.1.7 ◽

1943 ◽

Vol 77 (1) ◽

pp. 7-20 ◽

Cited By ~ 7

Author(s):

Frederik B. Bang

Keyword(s):

Influenza Virus ◽

Chick Embryo ◽

Synergistic Effect ◽

Swine Influenza Virus ◽

Chorioallantoic Membrane ◽

Swine Influenza ◽

Human Influenza ◽

Human Influenza Virus ◽

Hemophilus Influenzae ◽

The Individual

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.

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IMMUNOLOGICAL RELATIONSHIP BETWEEN THE SWINE AND HUMAN INFLUENZA VIRUSES IN SWINE

Journal of Experimental Medicine ◽

10.1084/jem.66.2.151 ◽

1937 ◽

Vol 66 (2) ◽

pp. 151-168 ◽

Cited By ~ 11

Author(s):

Richard E. Shope

Keyword(s):

Influenza Virus ◽

Influenza Infection ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Influenza Viruses ◽

Human Influenza ◽

Human Influenza Virus ◽

Immunological Relationship ◽

Cross Immunity ◽

The Cross

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.

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

Journal of Experimental Medicine ◽

10.1084/jem.63.5.645 ◽

1936 ◽

Vol 63 (5) ◽

pp. 645-653 ◽

Cited By ~ 25

Author(s):

Thomas Francis ◽

Richard E. Shope

Keyword(s):

Influenza Virus ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Influenza Viruses ◽

Human Influenza ◽

Human Influenza Virus ◽

Neutralizing Capacity ◽

Heterologous Virus

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.

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STUDIES WITH HUMAN INFLUENZA VIRUS CULTIVATED IN ARTIFICIAL MEDIUM

Journal of Experimental Medicine ◽

10.1084/jem.63.6.803 ◽

1936 ◽

Vol 63 (6) ◽

pp. 803-811 ◽

Cited By ~ 26

Author(s):

T. P. Magill ◽

Thomas Francis

Keyword(s):

Influenza Virus ◽

Neutralizing Antibodies ◽

The Other ◽

In Vitro Cultivation ◽

Human Influenza ◽

Artificial Medium ◽

Human Influenza Virus ◽

Simplified Procedure ◽

Culture Virus

The in vitro cultivation of strains of human influenza virus has been successfully conducted through a prolonged series of successive transfers. The cultivated virus has retained the antigenic and immunological properties which characterized the animal passage virus from which it was derived. The culture virus is still virulent for mice and ferrets; it is capable of inducing an active state of immunity in animals vaccinated subcutaneously or intraperitoneally; it elicits specific neutralizing antibodies in the serum of infected or vaccinated animals. The virus has been successfully cultivated to date only in the presence of oxygen; when conditions of reduced oxygenation are imposed by the use of vaseline seal, with or without the addition of cystein, multiplication of the virus is not supported. On the other hand, it has been possible to cultivate the virus in the medium of Li and Rivers in ordinary test tubes. This affords a greatly simplified procedure, since the interval between transfers may be prolonged. The results of neutralization tests with various sera and the culture virus are presented and discussed.

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Positive Selection in CD8+T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

Journal of Virology ◽

10.1128/jvi.01571-15 ◽

2015 ◽

Vol 89 (22) ◽

pp. 11275-11283 ◽

Cited By ~ 27

Author(s):

Heather M. Machkovech ◽

Trevor Bedford ◽

Marc A. Suchard ◽

Jesse D. Bloom

Keyword(s):

T Cells ◽

Influenza Virus ◽

T Cell ◽

Positive Selection ◽

Swine Influenza ◽

Selective Advantage ◽

Influenza Viruses ◽

T Cell Epitopes ◽

Human Influenza ◽

Human Influenza Virus

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.

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