DIFFERENCES IN REPLICATION AND CYTOPATHOGENICITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) ARE NOT DETERMINED BY LONG TERMINAL REPEATS (LTR)

The growth properties of molecular clones of a highly cytopathic Zairian HIV1-NDK and prototype viruses were compared to correlate genetic variations with biological changes. The cloned HIVi-NDK retained the highly replicating cytopathic phenotype and formed larger syncytia than the prototype. One of the major differences in the alignment of the nucleotide sequence of the HIVi-NDK and HIV1-BRU prototypes was localized in the negative regulatory element (NRE) of the long terminal repeat (LTR). In a chloramphenicol acetyl transferase (CAT) assay, we failed to detect a significant difference between LTR promoter activity of the prototype and HIVl-NDK, suggesting that the LTR of both phenotypes had a similar function. The complete recombinant provinus DNA molecules bearing HIVi LTR derived from one phenotype and the rest of the genomes from the other phenotype were constructed and transfected. The high cytopathogenicity of both the original and the chimeric viruses was correlated with the high speed of virus replication. Cytopathogenicity, morphology of syncytia, and replication kinetics of the recombinant viruses were determined by the functions coded within an internal part of HIVi genome, covering the gag to env region, which were, however, not within LTR. © 1990.