Document 0203 DOCN M9440203 TI Genetic analysis of the human immunodeficiency virus type 1 integrase protein. DT 9404 AU Shin CG; Taddeo B; Haseltine WA; Farnet CM; Division of Human Retrovirology, Dana-Farber Cancer Institute,; Boston, Massachusetts 02115. SO J Virol. 1994 Mar;68(3):1633-42. Unique Identifier : AIDSLINE MED/94149854 AB 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. DE Amino Acid Sequence Animal Base Sequence Cells, Cultured Conserved Sequence DNA Mutational Analysis DNA Nucleotidyltransferases/*GENETICS DNA, Viral/ANALYSIS HIV-1/*ENZYMOLOGY/GROWTH & DEVELOPMENT/GENETICS Molecular Sequence Data Morphogenesis Point Mutation Protein Processing, Post-Translational Retroviridae Proteins/BIOSYNTHESIS Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Viral Envelope Proteins/*GENETICS/SECRETION Virion/GROWTH & DEVELOPMENT *Virus Integration Virus Replication JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).