GENETIC INTERACTIONS BETWEEN ANIMAL VIRUSES 283 



character, such as SW, strains in which neuropathogenicity was combined 

 with the other serological type. 



Owing to the striking and unusual character of neuropathogenicity in an 

 influenza virus, a large proportion of subsequent work in our own and other 

 laboratories has made use of a neuropathogenic WS strain as one "parent" in 

 recombination experiments. 



In Melbourne we found NWS not particularly suitable for work in chick 

 embryos and changed in 1951 to the embryo-pathogenic strain WSE. With 

 MEL/WSE mixtures a high yield of recombinants could be obtained either in 

 intact embryos or in de-embryonated eggs. Extension of the work in various 

 laboratories soon uncovered a variety of phenomena in addition to the 

 transfer of neuropathogenicity from one serological type of virus to another. 

 These include: 



(1) The variable expression of neuropathogenicity in recombinants obtained 

 from a neurotropic and a non-neurotropic strain (Burnet and Edney, 1951). 

 In many such strains overt neuropathogenicity is shown only in mice less 

 than a week old (Lind and Burnet, 1957b). 



(2) The association of other changes with the transfer of neuropathogenicity 

 (Burnet and Lind, 1951a) leading to development of the concept of two 

 linkage groups in the MEL/WSE system (Burnet and Lind, 1952). 



(3) The production of "doubly neutralized" hemagglutinin in the primary 

 harvest of infections by mixtures of two serological types (Fraser, 1953; 

 Hirst and Gotlieb, 1953). 



(4) The demonstration of heterozygosity in virus showing double neutraliza- 

 tion (Gotlieb and Hirst, 1954; Lind and Burnet, 1957a). 



(5) The production of recombinants from mixtures of one active virus and 

 another inactivated by heat or ultraviolet irradiation (Burnet and Lind, 

 1954a; Baron and Jensen, 1955). 



(6) The observation of a variant in which the expression of several characters 

 was prevented apparently by a suppressor or modifier gene (Lind and Burnet, 

 1958). To this should be added the finding that in the myxovirus group ENA 

 is the only nucleic acid present in the infective particles (Ada and Perry, 1954; 

 Zillig et al., 1955). This makes the genetic behavior of influenza virus of great 

 general interest, inasmuch as it is the only genetic system yet available for 

 detailed study which camiot be based on a genetic code carried by DNA. 



B. Available Markers in the Influenza Viruses 



Genetic markers can be provided by any clearly demonstrable difference 

 between two strains which are capable of genetic interaction. Those chosen 

 will be determined essentially by the experience of the worker and the 

 availability of techniques in the laboratory undertaking the investigation. 

 Hirst and Gotlieb (1953) have virtually confined their attention to the two 



