Genetic analysis of the human immunodeficiency virus type 1 integrase protein.
Single-amino-acid changes in a highly conserved central region of the human immunodeficiency virus type 1 (HIV-1) integrase protein were analyzed for their effects on viral protein synthesis, virion morphogenesis, and viral replication. Alteration of two amino acids that are invariant among retroviral integrases, D116 and E152 of HIV-1, as well as a mutation of the highly conserved amino acid S147 blocked viral replication in two CD4+ human T-cell lines. Mutations of four other highly conserved amino acids in the region had no detectable effect on viral replication, whereas mutations at two positions, N117 and Y143, resulted in viruses with a delayed-replication phenotype. Defects in virion precursor polypeptide processing, virion morphology, or viral DNA synthesis were observed for all of the replication-defective mutants, indicating that changes in integrase can have pleiotropic effects on viral replication.
Shin
C G
CG
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Taddeo
B
B
Haseltine
W A
WA
Farnet
C M
CM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004279:DNA, Viral / Q000032:analysis; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D019426:Integrases; D008969:Molecular Sequence Data; D009024:Morphogenesis; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D012191:Retroviridae Proteins / Q000096:biosynthesis; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014771:Virion / Q000254:growth & development; D016662:Virus Integration; D014779:Virus Replication
D004279:DNA, Viral; C096362:L protein, hepatitis B virus; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D004254:DNA Nucleotidyltransferases; D019426:Integrases