Induc t ion of a Defective Virus Be JONATHAN P . STOYE * AND CHRISTOPH MORONI

Hybridization data indicate that germ line DNA from all mouse strains contains numerous endogenous retroviruses (1). In vivo expression of viral proteins and complete infectious viruses is variable and both mouse strain and tissue specific (2). Studies of the control of endogenous virus expression might be expected to provide insight into both the role of endogenous viruses in leukemogenesis and gene regulation in eukaryotic cells, A number of in vitro systems for induction of endogenous viruses have been described (reviewed in reference 3). The best studied of these systems is the addition of the halogenated pyrimidine derivatives bromodeoxyuridine (BrdU) 1 and iododeoxyuridine (IdU) to mouse fibroblasts (4), treatments that have been shown to induce both ecotropic and xenotropic viruses. Induction is apparently dependent on BrdU or IdU incorporation into cellular DNA (5). It has been shown that ecotropic virus inducibility maps to different chromosomes in different strains of mice (6-8). In contrast, xenotropic virus induction is controlled by an allelic locus on chromosome 1 in several strains of mice (9, 10). We are interested in the control of retroviral expression in lymphocytes, the cells normally transformed by C-type viruses. It has been shown that lymphoid cells activated in a graft versus host reaction produce endogenous virus probably solely of xenotropic host range (1 I). Similarly, it has been found that the activation of fresh, resting splenocytes in vitro with some B cell mitogens results in xenotropic virus induction (12, 13). Only B cell mitogens, such as lipopolysaccharide (LPS) and lipoprotein (LP), which are capable of stimulating B cells to differentiate into immunoglobulin-secreting plasma cells, induced virus; mitogens that stimulate only T cells did not (14, 15). If BrdU was added to cultures treated with inducing mitogens, a 5 to 15-fold increase in virus production as measured by reverse transcriptase was observed (14, 15). In contrast, BrdU addition to cells stimulated with noninducing mitogens did not result in virus release (14) even though BrdU becomes incorporated (16). Ecotropic virus production by mitogen-stimulated lymphocytes was not observed