Retroviral transduction of T-cell antigen receptor β-chain and myc genes

Abstract

Support for multistage models of oncogenesis has been provided by several highly leukaemogenic retrovirus isolates that have transduced more than one host cell gene^1–5. Where functional studies have been performed, these retroviral oncogenes show synergy for in vitro transformation and leukaemogenesis^6,7. In naturally occurring feline leukaemias associated with feline leukaemia virus (FeLV), retroviral transduction of myc is a frequent oncogenic mechanism^8–10. But evidence suggesting that the FeLV v-myc genes might be insufficient for leukaemogenesis was provided by the latency (12 weeks) and clonality of FeLV/v-myc-induced tumours and the absence of demonstrable in vitro transformation by these viruses¹¹. In the search for secondary leukaemogenic events in FeLV/v-myc tumours, we have identified a case of FeLV transduction of a T-cell antigen receptor β-chain gene. The proviruses carrying this gene (which we have named v-tcr) were a separate population from those carrying v-myc. In its normal role, the T-cell receptor β-chain forms part of a multimeric complex involved in antigen recognition^12–14 and T-cell activation^15,16. We suggest that v-tcr is a novel viral oncogene which assisted v-myc in the genesis of a naturally occurring case of thymic lymphosarcoma.