Suppression of Rous sarcoma virus-induced tumor formation by preinfection with viruses encoding src protein with novel N termini.
Two recovered avian sarcoma viruses (rASVs), rASV157 and rASV1702, encode src products which contain novel, nonmyristoylated N-terminal amino acids. These viruses transform chicken embryo fibroblasts and cause tumors in chicks. However, the tumors rASVs induce are small and regress within 2 weeks. To determine whether this regression results from weak tumorigenicity or from the active immunity of the host, we injected 1-week-old chicks with rASV and several days later injected the chicks with challenge virus of a different subgroup. Of the rASV1702-preinfected chicks challenged 5 days later with Rous sarcoma virus (RSV), 40% showed no subsequent tumor formation and 60% formed tumors which regressed within 1 week. The potency of this protective effect depended on the dosage of preinfection virus used and increased as the interval between preinfection and challenge infection was lengthened (when the interval was 9 days, none of the challenged chicks formed tumors). rASV157-preinfected chicks challenged with RSV after 9 days showed only partial protection: 42% formed tumors which regressed, whereas 58% formed tumors which continued to grow. Challenging rASV-preinfected chicks with Fujinami sarcoma virus or a RSV vector encoding the v-fps oncogene or polyomavirus middle T resulted in no suppression of tumor formation. Preinfection with src mutants or a RSV vector encoding polyomavirus middle T antigen, both of which induce slow-growing tumors, failed to elicit the protective effect. Finally, a novel N-terminal domain encoded by rASV1702 src was shown to be involved in but not sufficient for full protection. These data indicate that determinants on or induced by rASV157 and rASV1702 can elicit a potent protection against the tumorigenic potential of RSV-encoded p60v-src.
Gelman
I H
IH
Rockefeller University, New York, New York 10021-6399.
Hanafusa
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H
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D001358:Avian Sarcoma Viruses / Q000235:genetics* / Q000276:immunology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D005347:Fibroblasts; D015688:Oncogene Protein pp60(v-src); D012191:Retroviridae Proteins / Q000235:genetics* / Q000276:immunology; D001357:Sarcoma, Avian / Q000276:immunology*
D012191:Retroviridae Proteins; D015688:Oncogene Protein pp60(v-src)