INTERFERENCE BETWEEN ANIMAL VIRUSES 183 



particle itself, whether active or inactivated, has thus far been found capable 

 of triggering the mechanisms resulting in interference. The chief evidence, 

 other than quantitative correlations (see below), is as follows (Henle and 

 Henle, 1945b): (a) neutralization of interfering capacity by homologous 

 antiviral immune sera; (b) sedimentation of the interfering component along 

 with viral particles; (c) adsorption on and elution from fowl red cells along 

 with viral particles. Similar lines of evidence have been supplied by others for 

 influenza (Ziegler et ah, 1944) or NDV (Baluda, 1957). Data on the effects of 

 inactivating agents have significant, if more indirect, bearing on the subject. 

 Henle and Henle (1947) first demonstrated that interfering capacity of 

 influenza virus was less sensitive to UV-irradiation than infectivity or toxicity, 

 but more so than HA or CF activities. The relative effect of heat is similar 

 (Isaacs and Edney, 1950a). Baluda (1957) found that UV-irradiated NDV was 

 equally effective as interfering agent regardless of whether it had received an 

 average of 10, 50, or 100 units per particle. Powell and Pollard (1956) cal- 

 culated from data on the effect of ionizing radiation that only a minute 

 fraction of the influenza particle was responsible for interference. The nature 

 of this fraction remains unidentified, and Paucker and Henle (1958) have been 

 unable to induce the phenomenon with viral HA or S antigen obtained by 

 disintegration of virus particles with ether. The suggestion that incomplete 

 and standard particles interfere equally well with active influenza viruses 

 is in line with comparable radiation sensitivity found for the two kinds of 

 virus (Powell and Pollard, 1956). 



The only hint that materials other than viral particles themselves may play 

 a role in interference comes from the work by Isaacs et ah (1957) and Linden- 

 mann et ah (1957) on "interferon," a macromolecular substance produced in 

 and liberated from allantoic cells exposed to heat- or UV-inactivated influenza 

 virus. 1 Although the rate of interferon production corresponds closely to that 

 at which new viral antigens appear after infection with active virus, this 

 material has no recognizable viral properties; it is not neutralized by antiviral 

 immune serum; it is heat-labile (60°C. for 1 hour); it is not inactivated by 

 RNAase, partially by trypsin. Isaacs (personal communication) believes it to 

 be protein in nature, with no evidence for nucleic acid; it is not sedimentable 

 by centrifugation at 100,000^ for 30 minutes, but is retained by gradocol 

 membranes APD 0.6/z. This suggests an asymmetrical, perhaps filamentous, 

 shape. Interferon, added to normal CAM fragments prior to challenge with 

 homologous or heterologous viruses (including vaccinia virus (Depoux and 

 Isaacs, 1954a,b)), inhibits multiplication of the latter. 



1 An earlier observation by Lennette and Koprowski (1946) should be mentioned: 

 The supernatant fluid or tissue extract prepared from 24-hour tissue cultures infected 

 with 17DD yellow fever virus contained non-viral material (passing ultrafilter 12 myn 

 APD), which inhibited multiplication of West Nile virus. Unfortunately, this 

 observation was not followed up. 



