Replication of enhancer-deficient amphotropic murine leukemia virus in human cells

Amphotropic murine leukemia virus (MLV) replicates in cells from various ma mmalian species, including humans, and is a potential contaminant in MLV ve ctor preparations for human gene transfer studies. The generation of replic ation-competent virus is considered less likely with vectors that delete th e viral transcription elements. This conclusion is based on data obtained i n rodents, where MLV replication depends on the expression of viral genes u nder the control of 75-bp enhancer elements in the long terminal repeat. We demonstrate here that in some human cells replication of amphotropic MLV i s possible in the absence of these enhancer elements. Replication of the en hancer-deficient virus MLV(MOA)DeltaE is observed in selected human sarcoma and B lymphoma lines and proceeds at a lower rate than that of the intact virus. No insertion of a foreign promoter or enhancer into the long termina l repeat was detected. Our data suggest the presence of a secondary enhance r element within the MLV provirus that can in selected human cells mediate virus transcription and replication in the absence of the 75-bp U3 enhancer s.