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 HIV1-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 HIV1-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 HIV1-NDK, suggesting that the LTR of both phenotypes had a similar function. The complete recombinant provirus DNA molecules bearing HIV1 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 HIV1 genome, covering the gag to env region, which were, however, not within LTR.
Hirsch
I
I
Unité de Recherches Inserm sur les Rétrovirus et Maladies Associées, U 322, Campus Universitaire de Luminy, Marseille, France.
Spire
B
B
Tsunetsugu-Yokota
Y
Y
Neuveut
C
C
Sire
J
J
Chermann
J C
JC
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D014644:Genetic Variation; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014162:Transfection; D014774:Virulence; D014779:Virus Replication
D015500:Chloramphenicol O-Acetyltransferase