Lymphocyte-virus interactions. Identification of a restriction fragment permitting virus replication in lymphocytes.

We are interested in understanding the effects of virus infection on lymphocyte function. To approach this question, we used a unique system of two genetically related leporipoxviruses to generate recombinants. One of these viruses, malignant fibroma virus (MV), replicates in many different cell types, including lymphocytes. The other, Shope fibroma virus (SFV), replicates principally in fibroblasts, but cannot replicate in lymphocytes. Fibroblasts infected with SFV received restriction fragments from MV by transfection. Recombinant viruses were selected in vitro for their ability to replicate in lymphocytes. By these means we have identified one restriction fragment, the 10.8-kb BamHI "C" fragment, capable of transferring from MV to SFV the ability to replicate in lymphocytes. A family of recombinants bearing different sized inserts of this restriction fragment has been isolated and is being characterized. Lymphocytotropic recombinants bearing portions of this restriction fragment produce colony morphology in vitro intermediate between MV's plaques and SFV's foci. On the basis of their ability to grow in and suppress mitogen responsiveness of lymphocytes, these recombinants may be classified into four different groups. Group 1 viruses are the most immunosuppressive, whereas those of group 4 are least. These traits correlate with ability to replicate in lymphocytes. Genetic analysis of recombinants indicates that the most immunosuppressive recombinants do not necessarily contain the most fragment C DNA. Therefore, we have identified a restriction fragment, one or more of the genes of which are sufficient to allow an otherwise nonlymphocytotropic virus to replicate in lymphocytes. Additional genetic and immunologic analysis should permit us to determine the structure and function of the protein responsible for this effect.