scholarly journals AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM

1953 ◽  
Vol 97 (5) ◽  
pp. 601-625 ◽  
Author(s):  
Richard E. Shope

A culture of P. funiculosum isolated on Guam proved capable of elaborating a substance which exerted a favorable therapeutic effect against swine influenza virus infections in white mice. The culture was extremely variable and irregular in its production of the antiviral substance, and during maintenance in the laboratory for several years gradually lost this property. Efforts to restore it were unsuccessful. Subsequently it was found that the mold elaborated a substance, now designated helenine, which is therapeutically effective against Columbia SK encephalomyelitis virus infections in mice. Helenine appears to differ from the substance earlier procured from the mold, which was active against swine influenza virus infections in mice. It is frequently present in greater or lesser amount in the fluid portions of stationary cultures of P. funiculosum but is more regularly obtained and in larger amount, from the cellular components of the pellicles. When liberated from these latter by mechanical bruising and fracturing, it goes into solution in the culture fluids. It is precipitable from aqueous solution by 50 per cent acetone. Infected mice injected with helenine in amounts less than the amount which produces a maximal therapeutic effect exhibit a dosage response. Increasing the dose above the optimum fails to increase the therapeutic effect. Helenine exerts its maximum effect when given within the first 10 hours after viral infection but its influence is apparent even when treatment is delayed for up to 24 hours. It is not effective against massive amounts of virus and gives the best therapeutic results when used in the treatment of animals infected with from 10 to 1000 fatal doses of virus. Treatment of infected mice with helenine delays the entrance of virus into their brains for from 24 to 48 hours. The mechanism by which helenine exerts its therapeutic effect against SK virus is not known but the findings presented suggest either that it causes an inhibition or interruption of multiplication of the virus, slowing down the whole process of infection and spread to the central nervous system, or that in some way it interferes temporarily with the neuroinvasiveness of the virus.

1984 ◽  
Vol 20 (4) ◽  
pp. 833-835 ◽  
Author(s):  
C C Dacso ◽  
R B Couch ◽  
H R Six ◽  
J F Young ◽  
J M Quarles ◽  
...  

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.


1955 ◽  
Vol 102 (5) ◽  
pp. 567-572 ◽  
Author(s):  
Richard E. Shope

Twenty-five swine, infested with lungworms infected with masked swine influenza virus, were exposed to adverse weather conditions on one or more occasions. Of these, 4 came down with apparent swine influenza, while 6 others developed serological evidence of infection with swine influenza virus. The remaining 15 prepared swine, as well as 8 lungworm-free control swine, failed to show evidence of swine influenza virus infection, despite repeated exposures to adverse weather. The data presented indicate that, in the 10 swine in which swine influenza virus infections were elicited, some feature of the weather to which the animals were exposed was responsible for provoking masked influenza virus to infectivity. The exact constituent of the meteorological complex comprising "weather", responsible for the provocation, cannot be determined from the data obtained.


2014 ◽  
Vol 64 (1) ◽  
pp. 10-23
Author(s):  
Aleksandar Mašić ◽  
Niziti Woldeab ◽  
Carissa Embury-Hyatt ◽  
Yan Zhou ◽  
Shawn Babiuk

Abstract The 2009 outbreak of H1N1 influenza A viruses in humans underscored the importance of pigs in influenza A virus evolution and the emergence of novel viruses with pandemic potential. In addition, influenza A virus infections continued to cause production losses in the agricultural industry resulting in a significant drop of profit. The primary method to control influenza A virus infections in pigs is through vaccination. Previously we demonstrated that two doses of an elastase-dependent live attenuated swine influenza virus administered by either the intratracheal or intranasal route can provide a high degree of protection in pigs against challenge with both homologous and different heterologous swine influenza viruses. Here we report the protection efficacy of a single dose elastase-dependent live attenuated swine influenza virus administered by the intranasal route against challenge with homologous subtypic H1N1 2009 pandemic swine-like influenza virus. Protection was observed in the absence of neutralizing antibodies specific for H1N1 2009 in sera.


1941 ◽  
Vol 74 (1) ◽  
pp. 49-68 ◽  
Author(s):  
Richard E. Shope

1. The swine lungworm can serve as intermediate host in transmitting swine influenza virus to swine. The virus is present in a masked non-infective form in the lungworm, however, and, to induce infection, must be rendered active by the application of a provocative stimulus to the swine it infests. Multiple intramuscular injections of H. influenzae suis furnish a means of provoking infection. Swine influenza infections can be provoked in properly prepared swine during the autumn, winter, and spring, but not during the summer. The phenomenon, while not regularly reproducible, occurs in well over half the experiments conducted outside the refractory period of summer. No explanation for the failures is apparent. 2. The virus can persist in its lungworm intermediate host for at least 2 years. 3. Swine infected with swine influenza virus by way of the lungworm intermediate host exhibit a more pronounced pneumonia of the posterior lobes of the lung than do animals infected intranasally with virus. The situation of the worms providing the virus will account for this. 4. Occasional swine infested with lungworms carrying influenza virus fail to become clinically ill after provocation but instead become immune. In these it is believed that lungworms containing the virus are localized outside the respiratory tract at the time of provocation. 5. It is believed that the experiments described furnish an explanation for the findings recorded in the preceding paper, in which swine influenza virus infections were induced in apparently normal swine by multiple injections of H. influenzae suis. 6. In a single experiment swine lungworms failed to transmit hog cholera virus.


1943 ◽  
Vol 77 (2) ◽  
pp. 127-138 ◽  
Author(s):  
Richard E. Shope

1. The presence of masked swine influenza virus has been demonstrated in lungworm larvae from earthworms dug on Midwestern farms. 2. Swine influenza virus infections were provoked in 2 of 3 swine obtained from an Iowa farm during an interepizootic period. 3. The evidence presented has been interpreted as indicating that the swine lungworm is the reservoir and intermediate host for swine influenza virus in the field. 4. A concept of the epidemiology of swine influenza in which the causative virus is represented as being maintained and disseminated in a masked form by its lungworm intermediate host has been presented.


JAMA ◽  
1991 ◽  
Vol 265 (4) ◽  
pp. 478 ◽  
Author(s):  
Diana L. Wells

1943 ◽  
Vol 77 (2) ◽  
pp. 111-126 ◽  
Author(s):  
Richard E. Shope

1. During a 3 year study of the lungworm as intermediate host for the swine influenza virus 98 transmission experiments, using 216 swine, have been conducted. Of these, 50 gave negative results. In the remaining 48, transmission of swine influenza virus by way of the lungworm was demonstrated in one or more animals of each experiment. Irregularities in the results would appear to be due not so much to lack of transmission of masked virus by the lungworms as to failure to evoke its pathogenic capabilities. 2. The stimulus of choice that was most successful in the provocation of swine influenza consisted of multiple intramuscular injections of H. influenzae suis. In several experiments pigs developed swine influenza virus infections 9 to 17 days after infestation with infected lungworms in the absence of any known provocative stress. In these instances an immune response of the swine to the lungworms themselves is suspected of having furnished the provocation. 3. During May, June, July, and August, swine prepared by the ingestion of lungworms carrying virus were absolutely refractory to the provocation of influenza, and they were relatively refractory in September and October. The masked virus was activated most readily during the first 4 months of the year. 4. In a single experiment we succeeded in demonstrating by direct means the presence of swine influenza virus in the neighborhood of lungworms at the base of the lung at a time when the virus was not demonstrable anywhere else in the respiratory tract. 5. Masked swine influenza virus was found to be present in lungworm ova obtained either from the respiratory tracts or the feces of infected swine. 6. In a number of instances, masked swine influenza virus has been found to persist for over a year in lungworm larvae within the earthworm intermediate hosts, and in one case its presence was demonstrated after 32 months. 7. Two varieties of a single species of earthworm, namely, Allolobophora caliginosa f. typica (Savigny) and A. caliginosa f. trapezoides (Dugès), have been found separately capable of serving as intermediate hosts for virus-infected lungworms. 8. Lungworm ova, obtained from convalescent swine which are no longer carrying swine influenza virus in infectious form in their respiratory tracts, contain masked virus.


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