Recovery of Glycosylated gag Virus from Mice Infected with a Glycosylated gag-Negative Mutant of 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.