Inhibition of Rous Sarcoma Virus-induced Transformation by Preinfection with Rhabdoviruses

Abstract

SUMMARYIn vivo preinfection of chicks with rabies virus (RV) or vesicular stomatitis virus (VSV) ts 1026 inhibits tumour formation after superinfection with Rous sarcoma virus (RSV). The degree of inhibition depends on the titre of the infecting viruses and the interval between rhabdovirus and RSV infection. In vitro, cells preinfected with VSV ts 1026 under non-permissive conditions and superinfected with RSV, are not transformed as judged by cell morphology, serum requirement for growth or the capacity to form colonies in soft agar, all these being the same as in uninfected cells. Doubly infected cells take up less deoxyglucose than cells infected with RSV only and more than cells infected with VSV only. RSV multiplication is inhibited in doubly infected cells: the supernatant fluid of these cells contains fewer focus-forming units and less reverse transcriptase activity than that of cells infected with RSV only. Doubly infected cells contain both VSV and RSV internal antigens 15 days after infection. The supernatant fluid of cells infected with VSV and maintained under non-permissive conditions inhibits transformation by RSV and multiplication of RSV, but not of VSV. Under non-permissive conditions, the rhabdoviruses undergo at least part of the infectious cycle, but no infectious virus is produced. RV antigen can be detected in the brain of parenterally infected chicks and VSV antigen in cells infected 15 days previously. We conclude that the inhibition of RSV multiplication and expression is probably due to one or more processes linked to the persistence of rhabdovirus components and that it cannot be attributed exclusively to interferon.

Viral products in cells infected with Vesicular Stomatitis virus and superinfected with Rous Sarcoma virus

“…RSV gag and env mRNAs are translated into precursor proteins which are cleaved through different smaller precursors into the mature structural proteins p 19, p 10, p27, p 12, and p 15 from the gag precursors, gp85 and gp 37 from the env precursor proteins [t 1, 9]. As expected from immunofluorescence experiments [20] cells infected with RSV and doubly infected cells contain RSVspecific antigens. The gag precursor pr 76, the env related proteins gp 85 and gp37, the gag related proteins p27, p 19, p 15, p 12, and p 10 are detected in RSV infected cells, as well as unidentified proteins migrating between gp 85 and pg 37; the latter could be abnormal cleavage products (Fig.…”

“…Recent reports describe the inhibition of pp 60 v-src and structural viral protein synthesis as well as inhibition of different transformation characteristics in RSV transformed cells treated with interferon (20-400 units per ml) [14,25], but this inhibition appears to be due mainly to a decrease in cell growth. Since infection of CEC does not induce interferon and does not inhibit cell growth [20], it is unlikely that the same mechanisms of inhibition are involved when cells are treated with interferon and when they are preinfected with VSV ts 1026; we are at present investigating this aspect of the inhibition of RSV induced transformation and RSV multiplication by preinfection with VSV.…”

“…VSV ts 1026 infection can induce interferon in rat and to a lesser degree in hamster embryo cells [8], but not in CEC [20]. Recent reports describe the inhibition of pp 60 v-src and structural viral protein synthesis as well as inhibition of different transformation characteristics in RSV transformed cells treated with interferon (20-400 units per ml) [14,25], but this inhibition appears to be due mainly to a decrease in cell growth.…”

“…Both VSV and RSV antigens were found in the doubly infected cells up to 15 ds after infection. The supernatant of VSV infected cells also inhibited RSV induced transformation and RSV multiplication but did not block VSV wt multiplication; therefore, the inhibition of transformation and multiplication could not be attributed exclusively to interferon [20].Since the appearance of the transformed phenotype in RSV infected cells is the consequence of molecular events--the integration, transcription and translation of the v-src gene--we tried to determine which, if any, of these processes were inhibited in cells infected with both VSV ts 1026 and RSV. In this report we describe the viral products in cells infected with RSV, VSV ts 1026 and with both viruses.…”

“…The supernatant of VSV infected cells also inhibited RSV induced transformation and RSV multiplication but did not block VSV wt multiplication; therefore, the inhibition of transformation and multiplication could not be attributed exclusively to interferon [20].…”