Document 0508
 DOCN  M9480508
 TI    Human immunodeficiency virus type 1 integrase: effect on viral
       replication of mutations at highly conserved residues.
 DT    9410
 AU    Cannon PM; Wilson W; Byles E; Kingsman SM; Kingsman AJ; Department of
       Biochemistry, University of Oxford, United Kingdom.
 SO    J Virol. 1994 Aug;68(8):4768-75. Unique Identifier : AIDSLINE
       MED/94309139
 AB    Sequence comparisons of the integrase (IN) proteins from different
       retroviruses have identified several highly conserved residues. We have
       introduced mutations at 16 of these sites into the integrase gene of
       human immunodeficiency virus type 1 and analyzed the phenotypes of the
       resulting viruses. The viruses were all normal for p24 content and
       reverse transcriptase activity. In addition, all of the mutants could
       infect T-cell lines and undergo reverse transcription, as assessed by
       PCR analysis. Most of the mutant viruses also had normal Western blot
       (immunoblot) profiles, although three of the mutations resulted in
       reduced signals for IN relative to the wild type on the immunoblots and
       mutation of residue W235 completely abolished recognition of the protein
       by pooled sera from human immunodeficiency virus type 1-positive
       patients. Mutations that have previously been shown to abolish activity
       in in vitro studies produced noninfectious viruses. The substitution of
       W235 was notable in producing a noninfectious virus, despite previous
       reports of this residue being nonessential for IN activity in vitro
       (A.D. Leavitt, L. Shiue, and H.E. Varmus, J. Biol. Chem. 268:2113-2119,
       1993). In addition, we have identified four highly conserved residues
       that can be mutated without any affect on viral replication in T-cell
       lines.
 DE    Amino Acid Sequence  Base Sequence  Conserved Sequence  DNA
       Nucleotidyltransferases/GENETICS/*METABOLISM  Human  HIV Long Terminal
       Repeat  HIV-1/*ENZYMOLOGY/GENETICS/PHYSIOLOGY  Immunodominant
       Epitopes/GENETICS/IMMUNOLOGY  Leucine Zippers/GENETICS  Molecular
       Sequence Data  Mutagenesis, Site-Directed  RNA, Viral  Support, Non-U.S.
       Gov't  T-Lymphocytes/MICROBIOLOGY  Viral Proteins/ANALYSIS  Virus
       Integration  *Virus Replication/GENETICS  Zinc Fingers/GENETICS  JOURNAL
       ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).