GENETIC-ANALYSIS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASEPROTEIN

Single-amino-acid changes in a highly conserved central region of the human immunodeficiency virus type 1 (HIV-1) integrase protein were ana lyzed for their effects on viral protein synthesis, virion morphogenes is, and viral replication. Alteration of two amino acids that are inva riant among retroviral integrases, D116 and E152 of HIV-1, as well as a mutation of the highly conserved amino acid S147 blocked viral repli cation in two CD4(+) human T-cell lines. Mutations of four other highl y conserved amino acids in the region had no detectable effect on vira l replication, whereas mutations at two positions, N117 and Y143, resu lted in viruses with a delayed-replication phenotype. Defects in virio n precursor polypeptide processing, virion morphology, or viral DNA sy nthesis were observed for all of the replication-defective mutants, in dicating that changes in integrase can have pleiotropic effects on vir al replication.