RABBIT-CELLS EXPRESSING HUMAN CD4 AND HUMAN CCR5 ARE HIGHLY PERMISSIVE FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

To evaluate the feasibility of using transgenic rabbits expressing CCR 5 and CD4 as a small-animal model of human immunodeficiency virus type 1 (HIV) disease, we examined whether the expression of the human chem okine receptor (CCR5) and human CD4 would render a rabbit cell line (S IRC) permissive to HIV replication. Histologically, SIRC cells express ing CD4 and CCR5 formed multinucleated cells (syncytia) upon exposure to Bat, a macrophagetropic strain of HIV that uses CCR5 for cell entry . Intracellular viral capsid p24 staining showed abundant viral gene e xpression in Bat-infected SIRC cells expressing CD4 and CCR5. In contr ast, neither SIRC cells expressing CD4 alone nor murine 3T3 cells expr essing CCR5 and CD4 exhibited significant expression of p24. These sta bly transfected rabbit cells were also highly permissive for the produ ction of virions upon infection by two other CCR5-dependent strains (J R-CSF and YU-2) but not by a CXCR4-dependent strain (NL4-3). The funct ional integrity of these virions,vas demonstrated by the successful in fection of human peripheral blood mononuclear cells (PBMC) with viral stocks prepared from these transfected rabbit cells. Furthermore, prim ary rabbit PBMC were found to be permissive for production of infectio us virions after circumventing the cellular entry step. These results suggest that a transgenic rabbit model for the study of HN disease may be feasible.