Single Amino Acid Substitution ( 58Pro → Ser) in HTLV-I Tax Results in Loss of Ras Cooperative Focus Formation in Rat Embryo Fibroblasts

Abstract

Two tax genes cloned from a healthy HTLV-I carrier in whom the viral genome is clonally integrated into peripheral CD4 +CD8 + cells showed a considerable difference in ras cooperative focus forming ability in rat embryo fibroblasts (REF). Sequence analysis revealed differences in two codons of the two genes, SH-1tax and SH-2tax. Studies using recombinants between these two tax genes showed that the deficiency in ability of SH-1tax to cooperate with ras in focus formation in REF was caused by a 58 Pro → Ser substitution. This amino acid substitution did not affect other tax functions such as colony formation in soft agar, focus formation in Rat-1 cells, immortalization of REF, and transcriptional activation through the CREB/ATF and NFkB/ rel pathways. These results suggest that the domain of tax required for cooperative focus formation with ras in primary rat fibroblasts may be different from those required for other tax functions.