Levels of complement during interferon induction.

Further data were obtained in support of the finding that the levels of interferon and complement show a negative correlation after induction of interferon in vivo. Experiments with selective chelating agents showed that the activation of complement occurs by the by-pass mechanism. Preliminary results indicate that interferon itself can reduce the level of complement in vivo. Experiments are underway to verify in rats the results obtained in mice.

Consumption of complement in chelated and nonchelated guinea pig serum after challenge with some viral and nonviral interferon inducers.

The consumption of complement observed during the induction of interferon by various inducers may proceed via the alternate pathway. The alternate pathway requires the presence of Mg ions in the medium while Ca ions may be absent.

Interferon-hyporesponsiveness in mice in connection with dose interval and site of administration of Newcastle disease virus. Reflexion in serum complement levels.

Intraperitoneal administration of Newcastle disease virus (NDV) resulted in enhanced serum levels of complement not accompanied by an increase of interferon levels, when measured at 24 hours' intervals. On the other hand, intravenous injection of NDV caused a drop of complement levels of short duration with an accompanying increase of interferon levels. Hyporeactivity to induction of serum interferon could not be achieved by intraperitoneal administration of NDV, but an incomplete hyporeactivity could be achieved by intravenous administration of NDV. It might be assumed that production of interferon in mice occurs in different separated compartments depending on the route of inoculation of the inducer.

Experimental infection of weanling pigs with A-swine influenza virus. 2. The shedding of virus by infected animals.

As part of a study described in a previous paper observations were made to determine whether and for how long experimentally infected young pigs would transmit their infection to new groups of weanlings maintained in contact with them. When groups of 4 or 5 susceptible weanlings 2-3 months old were placed in contact for a month with infected pigs 42 days or 3, 6, 9 or 12 months after experimental infection, no antibody rises were observed in the contact pigs. However, a strain of virus identical with the infecting strain was isolated from lung suspensions from 2 of the 5 contact pigs exposed to pigs infected 3 months previously. Possible sources of technical error such as laboratory contamination could be almost certainly excluded. It is considered that a shedder state of virus had occurred some time during the fourth month following experimental infection. There was suggestive serological evidence that the shed virus acted as a booster dose to previously infected pigs.

Experimental infection of weanling pigs with A-swine influenza virus. I. Epidemiology and serological response.

Naturally occurring swine influenza is caused by a strain of virus closely related to influenza strains isolated from man in 1918 and later. Information is lacking on certain aspects of the epidemiology of swine influenza that, if obtained, might shed some light on the epidemiology of human influenza, particularly with respect to inter-epidemic reservoirs and shedders of the virus. In a first series of experiments undertaken by the authors pigs were experimentally infected intranasally with swine influenza virus and the course of clinical infection, spread by contact, and the serological response of infected animals were studied. Observations were also made on persons in contact with the infected swine to determine whether cross-transmission occurred. Respiratory and feverish clinical signs of the disease were observed in infected animals. Contact infection of several animals in the same piggery occurred, as revealed by serological tests, although the contact-infected pigs showed no clinical signs. There was some but not highly significant serological evidence of human infection in laboratory workers and animal handlers exposed to swine influenza virus. Some pigs infected as weanlings developed specific antibodies that lasted for 1(1/2) years of observation. Antibody titres decreased markedly towards the end of 1 year in animals of a lower age at the time of infection (42 days old), as compared with older animals (52-77 days) in which there were lesser decreases in titre.

Experimental infection of weanling pigs with A-swine influenza virus. 3. Immunity in piglets farrowed by antibody-bearing dams experimentally infected a year earlier.

Pigs experimentally infected as weanlings with swine influenza virus, as described in previous papers, were bred from when mature. Attempts to isolate virus at parturition from the placenta and from different organs of some of the piglets immediately after birth gave negative results. Antibody levels were determined in the sows and remaining piglets at different times after birth, and the clinical course, immunity and antibody formation were studied in some of the piglets challenged with swine influenza virus 10 days after birth. The levels were found to be generally higher in the sows than those in their offspring. Specific antibodies were detected in piglets that had presumably not ingested colostrum, but the possibility of unobserved ingestion of colostrum could not be excluded. Colostrum-fed piglets had specific antibody in their sera; an increase in antibody titre occurred by the 10th day after birth, remained until the 20th day and decreased steadily to the 30th day. Colostrum-fed piglets receiving antibodies from immune dams were resistant to a challenge of virulent swine influenza virus, and did not respond with an antibody rise during a 30-day observation period after challenge.