A role for natural simian immunodeficiency virus and human immunodeficiency virus type 1 Nef alleles in lymphocyte activation

A T-lymphoid cell line termed 221 was derived from a rhesus monkey infected with herpesvirus saimiri, Growth of 221 cells was dependent on the addition of interleukin-2 (IL-2) to the culture medium, In the absence of IL-2, 221 cells arrested in G(0)-G(1) but did not die, Simian immunodeficiency virus (SIV) replicated efficiently in IL-2 stimulated 221 cells whether or not the nef gene was present. In the absence of IL-2, nef-containing SIV replicated 8 to 100 times more efficiently in 221 cells than did the same virus lacking nef, nef-containing virus preferentially stimulated the production of IL-2 from 221 cells, HIV-1 nef and v-ras genes, but not the c-ras gene, were shown to substitute functionally for SIV nef when tested as recombinant viruses in this assay system, These results demonstrate a role for natural nef in causing lymphoid cell activation, and they provide a system for delineating the biochemical mechanisms responsible for this activation.