FUSION ACTIVITY DISSOCIATED FROM REPLICATION ABILITY IN FELINE IMMUNODEFICIENCY VIRUS (FIV) IN HUMAN-CELLS

Multinucleated-giant-cell formation followed by cell killing was obser ved after cocultivation of the feline immunodeficiency virus (FIV)-pro ducing feline T-cell line 3201/FIV with various human cells, including T-cell fines carrying human T-cell lymphotropic virus type I (HTLV-I) . The susceptibility to giant cell formation varied with the cell line s tested. Cocultivation of irradiated 3201/FIV cells with MT-2 cells r esulted in giant cell formation as early as 2 h in culture, with strik ing resemblance to that induced by human immunodeficiency virus (HIV). MT-4 cells (HTLV-I positive) and H9 cells (HTLV-I negative) were less susceptible than MT-2 to the induction of syncytia. MOLT-4 cells (HTL V-I negative) had intermediate sensitivity to syncytia formation. No s yncytia were observed in the monocytic cell line U-937 (HTLV-I negativ e). Syncytia formation between 3201/FIV and MT-2 cells was inhibited b y polyclonal cat anti-FIV antisera but not polyclonal cat anti-feline leukemia virus (FeLV) antisera, goat anti-FeLV, uninfected specific-pa thogen-free cat serum, human anti-HTLV-I antisera, or normal human and goat serum. Concentrated cell-free FIV supernatant from 3201/FIV also induced giant cells of MT-2 cells that were indistinguishable from th ose induced by cocultivation. Giant cells and extensive celt killing a ssociated with giant cell formation declined and disappeared within 10 days. Surviving cells appeared to be of normal size and grew continuo usly without expressing FIV antigen or releasing infective virus. Alth ough Southern blot analysis using probes specific for FIV could not de tect proviral DNA in any of the five human cell lines cocultured with irradiated 3201/FIV cells, the polymerase chain reaction (PCR) techniq ue detected FIV-specific DNA in MOLT-4 cells. DNA from the FIV-PCR pos itive MOLT4 cells was PCR negative for endogenous FeLV-specific sequen ces, indicating that the MOLT-4 cell DNA was not contaminated with DNA from feline cells (i.e., 3201 cells). The FIV-MOLT-4 cells remained P CR positive for FIV after 40 passages, suggesting stable integration i n the human cell line. These findings indicate that FIV is capable of forming proviral DNA in human T-lymphoid cells by cocultivation, altho ugh this FIV-carrying human cell line failed to produce replication-co mpetent viruses.