The collagen repeat sequence is a determinant of the degree of herpesvirussaimiri STP transforming activity

Herpesvirus saimiri (WS) is divided into three subgroups, A, B, and C, base d on sequence divergence at the left end of genomic DNA in which the saimir i transforming protein (STP) resides. Subgroup A and C strains transform pr imary common marmoset lymphocytes to interleukin-2-independent growth, wher eas subgroup B strains do not. To investigate the nononcogenic phenotype of the subgroup B viruses, STP genes from seven subgroup B virus isolates wer e cloned and sequenced. Consistent with the lack of oncogenic activity of H VS subgroup B viruses, STP-B was deficient for transforming activity in rod ent fibroblast cells. Sequence comparison reveals that STP-B tacks the sign al-transducing modules found in STP proteins of the other subgroups, collag en repeats and an authentic SH2 binding motif. Substitution mutations demon strated that the lack of collagen repeats but not an SH2 binding motif cont ributed to the nontransforming phenotype of STP-B. Introduction of the coll agen repeat sequence induced oligomerization of STP-B, resulting in activat ion of NF-kappa B activity and deregulation of cell growth control. These r esults demonstrate that the collagen repeat sequence is a determinant of th e degree of HVS STP transforming activity.