SYNCYTIUM INDUCTION IN PRIMARY CD4(-CELL LINES FROM NORMAL DONORS BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES WITH NON-SYNCYTIUM-INDUCING GENOTYPE AND PHENOTYPE IN MT-2 CELLS() T)

Human immunodeficiency virus type 1 (HIV-1) isolates classified as syn cytium-inducing (SI) or non-SI (NSI) in the MT-2 T-cell line exhibit c haracteristic sequence differences in the V1-V2 and V3 regions of the env gene, Seven HIV-1 isolates were phenotyped as NSI or SI in the MT- 2 cell line, Unexpectedly, all four NSI viruses induced large syncytia 4 to 8 days postinoculation in a panel of five primary CD4(+) T-cell lines (including two clones) generated from the peripheral blood of no rmal donors by exposure to infectious HIV-1, inactivated HIV-1, or Eps tein-Barr virus, The primary T-cell lines yielded neither HIV-1 provir us nor infectious HIV by PCR analysis or exhaustive coculture with phy tohemagglutinin-treated blast cells, Three isolates (TC354, PK1, and P K2) were biologically cloned and retained their SI or NSI phenotypes i n MT-2 and primary T-cell lines, The biologically cloned provirus DNA was also used to clone and sequence the relevant V2 and V3 regions of the env genes, The amino acid sequences of the V2 and V3 regions were characteristic of patterns already reported for the NSI, switch NSI, a nd SI phenotypes, respectively, This evidence precludes the possibilit y that these results were due to contamination of the NSI isolates wit h SI virus. The results unequivocally indicate that HIV-1 isolates wit h the NSI genotype acid phenotype in MT-2 cells may actively induce sy ncytia in cloned CD4(+) T cells in vitro and support the view that dir ect cytopathic effects may contribute to the steady decline in CD4(+) T cells in asymptomatic HIV-1-seropositive patients without detectable SI virus.