Effect of pseudotype on Abelson virus and Kirsten sarcoma virus-induced leukemia

Abstract

Nonproducer cells transformed by Kirsten sarcoma virus (KiSV) or Abelson murine leukemia virus (A-MuLV) were infected with N- or NB-tropic helper viruses to rescue the defective transforming virus. The titer of the transforming viruses was determined on NIH/3T3 fibroblast-like cells and cell-free filtrates of virus stock were inoculated into newborn Fv-1nn mice. Friend, Moloney, and Rauscher group of MuLV (FMR) pseudotypes of KiSV induced an erythroid leukemia efficiently, while an endogenous helper (N35-MuLV) pseudotype of KiSV did not. FMR pseudotypes of A-MuLV induced the Abelson lymphoid leukemia, while the N35-MuLV or a Kirsten leukemia virus (Ki-MuLV) pseudotype did not. Pseudotypes of A-MuLV were used to infect bone marrow cells of Fv-1nn mice in vitro. The FMR pseudotypes transformed bone marrow cells at 40-100-fold higher frequency than the N35-MuLV or Ki-MuLV pseudotypes. Mixing experiments demonstrated that the addition of an effective helper, such as M-MuLV did not enhance lymphoid transformation by ineffective A-MuLV (N35-MuLV). The A-MuLV genome is responsible for hematopoietic cell transformation because a nonproducer clone of lymphoid cells, free of helper virus, was isolated. The data indicates that the pseudotype of A-MuLV determines its ability to transform hematopoietic cells.