Replication-defective Friend murine leukemia virus particles containing uncleaved gag polyproteins and decreased levels of envelope glycoprotein

Abstract

An erythroleukemia cell clone, 7C, which failed to produce reverse transcriptase-containing virions or infectious virus, was found to produce noninfectious virus particles by gradient banding of [3H]leucineand [3H]uridine-labeled virions. The RNA from the 7C virus was shown to consist of the normal 70S size component, which converted to 35S upon heat denaturation. In contrast, the 7C virion proteins showed multiple defects. Analysis of the virion proteins by gel electrophoresis demonstrated that the pr65 gag precursor was incorporated into the 7C virus and that the processing of this precursor was severely diminished. Polymerase proteins pr18O9a9-)" and prl2OPI' were also detected in virions, and a third possible polymerase protein, p70, was reduced in size compared to its normal counterpart, p80. Incorporation of the viral gp7O glycoprotein into particles was also reduced 10-fold, despite synthesis and incorporation of gp7O into the 7C cell membrane in normal amounts. Pulse-chase analysis of the synthesis of the viral gag and env proteins in 7C cells showed greatly reduced amounts of prl80g ,,OI,

Variation in p30-related proteins in gross virus-induced tumor cell lines derived from H-2 congenic mice

“…It is notable that other Friend virus-induced tumor cell lines which have been reported to have stopped producing infectious virus express the same two H-2 haplotypes, albeit on different genetic backgrounds (1, 4, 15), but too few cell lines have been studied to determine whether H-2-linked genes actually mediate this change. The data presented in this report show that the lesions in the nonproducer cell lines derived from GVinduced tumors involve gag protein processing and in that respect are similar to lesions found in nonproducer Friend virus-induced cell lines (1,5,15). Thus, these findings suggest that in these cell lines the mechanisms of conversion to the nonproducer phenotype may be related, which is consistent with the hypothesis that virus production may be regulated by the host cell.…”

“…The particles produced were not oncogenic in vivo, indicating that the alterations in viral proteins changed the biological behavior of the virions but not their ability to replicate. Cultured tumor cells of Friend virus origin which are negative in the XC assay and have gag protein defects have also been shown to produce viral particles (5). In other nonproducer Friend virus-induced cell lines, the absence of detectable Friend MuLV gag-gene products (1) accompanying decreased Friend MuLV-specific RNA expression (2) has been interpreted to mean that the 5'-end of the MuLV genome is deficient (1).…”

“…Too few cell lines have been studied to determine whether an H-2-linked gene(s) actually mediates the change to noninfectious status in vitro or to ascertain the molecular processes involved in the cessation of infectious virus production in these cell lines. However, the nonproducer Friend virus-induced cultured tumor cell lines which have been studied contain multiple changes in virus protein processing (1,5,15). Because both GV-and Friend virusinduced cell lines which have become nonproducers of infectious virus may nonetheless continue to express murine leukemia virus (MuLV)-encoded proteins (8,19), it is important to determine whether the molecular lesions related to virus production in the GV-induced nonproducer cell lines are similar to those observed in Friend virus-induced cell lines.…”