Species restriction of Herpesvirus saimiri and Herpesvirus ateles: Human lymphocyte transformation correlates with distinct signaling properties of viral oncoproteins

The potential of Herpesvirus saimiri (HVS) subgroups A, B and C and Herpesvirus ateles (HVA) to transform primary T cells to permanent growth in vitro is restricted by the primate host species and by viral variability represented by distinct viral oncoproteins. We now addressed the relation between the transforming potential of the different viruses and the signaling pathways activated by transiently expressed oncoproteins. Marmoset lymphocytes were transformed by all HVS subgroups as well as HVA, while transformation of human cells was restricted to HVS-C and, unexpectedly, HVA. NF-κB and Src-family kinase (SFK) activity was required for survival of all transformed lymphocytes. Accordingly, NF-κB was induced by oncoproteins of all viruses. In contrast, SFK-related signaling was detectable only for oncoproteins of HVS-C and HVA. Thus, the restricted transformation of human lymphocytes likely correlates with the specific SFK targeting by these oncoproteins. These results will enable further studies into novel SFK effector mechanisms relevant for T-cell proliferation.

Highlights► Marmoset lymphocytes are transformed by HVS-A, HVS-B, HVS-C and HVA. ► Human lymphocytes are only transformed by HVS-C and HVA. ► Survival of transformed cells requires NF-κB and Src-family kinase (SFK) activities. ► Oncoproteins of all virus strains activate NF-κB in transfected Jurkat T cells. ► Only HVS-C and HVA oncoproteins induce SFK-related signaling in transfected cells.