SIMIAN IMMUNODEFICIENCY VIRUS SIVSMMPBJ-1.9 INDUCES MULTINUCLEATED GIANT-CELL FORMATION IN HUMAN PERIPHERAL-BLOOD MONOCYTES

SIVsmmPBJ 1.9 is an extremely virulent clone of the simian immunodefic iency virus SIVsmmPBj 14 that causes an acute lethal disease in pigtai l macaques, with death occurring 6 to 8 days after infection. The dise ase is characterized by bloody mucoid diarrhea, lymphoid hyperplasia, and giant cell pneumonia. We have developed an in vitro model for the production of multinucleated giant cells (MGCs) in which peripheral bl ood monocytes rapidly fuse to form MGCs when cultured in lymphocyte-co nditioned medium and antibody against class II MHC. We have tested the effect of SIVsmmPBj on monocytes in our MGC model system. Peripheral blood mononuclear cells (PBMCs) from normal healthy human subjects, wh en cultured in the presence of anti-class II MHC monoclonal antibody a nd SIVsmmPBj 1.9, but not either alone, resulted in the formation of M GCs within 4 days. Experiments using Transwell chambers indicated that such MGCs are formed by fusion of monocytes, not by virus-induced fus ion of lymphocytes. SIVsmmPBj 1.9 is unique in inducing MGC formation in that other SIV and HIV isolates do not induce MGCs. Whereas SIVsmmP Bj 1.9 grown in PBMCs was a potent inducer of MGCs in the presence of anti-class II MHC antibody, SIVsmmPBj 1.9 grown in CEMx174 failed to d o so. Antibodies against IFN-gamma and TNF-alpha significantly inhibit ed SIVsmmPBj/anti-class II-induced formation of MGCs. These results in dicate that cytokines released in response to SIVsmmPBj 1.9, in conjun ction with antibodies to class II MHC, caused fusion of monocytes.