Infection by mink cell focus-forming viruses confers interleukin 2 (IL-2) independence to an IL-2-dependent rat T-cell lymphoma line.
The development of T-cell lymphomas in rodents infected with type C retroviruses has been linked to the generation of a class of envelope (env) recombinant viruses called mink cell focus-forming viruses (MCF viruses) in the preleukemic thymus. To determine whether infection by MCF viruses altered the growth phenotype of retrovirus-induced T-cell lymphomas, a Moloney murine leukemia virus-induced interleukin-2 (IL-2)-dependent rat T-cell lymphoma line (4437A) was infected with MCF-247, modified MCF-V33 (mMCF-V33), or NZB-xenotropic (NZB-X) virus. The effects of virus infection on the IL-2 dependence of these cells was examined by cultivating them in the absence of IL-2. After IL-2 withdrawal, the uninfected and NZB-X-infected cells went through a crisis period characterized by massive death. All the independently maintained cultures of MCF- and mMCF-V33-infected cells, on the other hand, became IL-2 independent without a crisis. All the polytropic virus-infected IL-2-independent cultures contained a population of cells that was polyclonal with regard to polytropic provirus integration. Over this polyclonal background each culture produced multiple clones of cells that were selected rapidly after IL-2 withdrawal. Furthermore, the resulting MCF- or mMCF-V33-infected IL-2-independent cells retained the expression of IL-2 receptor. These data show that MCF and mMCF-V33 viruses may alter the growth phenotype of a T-cell lymphoma line and suggest that their effect on cell growth may be due to the direct interaction of the MCF envelope glycoprotein with cellular components, perhaps the IL-2 receptor.
Tsichlis
P N
PN
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Bear
S E
SE
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D005434:Flow Cytometry; D005814:Genes, Viral; D007376:Interleukin-2 / Q000494:pharmacology*; D016399:Lymphoma, T-Cell / Q000276:immunology; D008908:Mink Cell Focus-Inducing Viruses / Q000235:genetics*; D008979:Moloney murine leukemia virus / Q000235:genetics; D010641:Phenotype; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology; D015183:Restriction Mapping
D007376:Interleukin-2; D015375:Receptors, Interleukin-2