Recovery of Glycosylated gag Virusfrom Mice Infected with aGlycosylated gag-Negative Mutantof Moloney Murine Leukemia Virus

Two independent pathways for gag gene expression exist in Moloney murine leukemia virus (M-MuLV). One begins with Pr65^gag that is processed and cleaved into the internal structural proteins of the virion. The other pathway begins with the glycosylated gag polyprotein, gPr80^gag gPr80^gag consists of Pr65^gag plus additional N-terminal residues and it is glycosylated. A glycosylated- gag-negative mutant of M-MuLV (Ab-X-MLV) was previously constructed and shown to replicate in tissue culture. To test for the importance of glycosylated gag in vivo, the Ab-X-MLV mutant was inoculated intraperitoneally into newborn NIH Swiss mice. Mutant-infected mice developed typical lymphoblastic lymphomas at rates comparable to wild-type M-MuLV at either high (2 x 10^4 XC pfu/animal) or low (2 x 10^2 XC pfu/animal) doses. However, when viral protein expression was examined in the resultant tumors, six out of six mice showed evidence of virus that had recovered gPr80^gag expression. These results suggest that glycosylated gag is important for M-MuLV propagation or leukemogenesis in vivo.