       Document 0100
 DOCN  M9630100
 TI    Conserved sequences in the carboxyl terminus of integrase that are
       essential for human immunodeficiency virus type 1 replication.
 DT    9603
 AU    Cannon PM; Byles ED; Kingsman SM; Kingsman AJ; Department of
       Biochemistry, University of Oxford, United Kingdom.
 SO    J Virol. 1996 Jan;70(1):651-7. Unique Identifier : AIDSLINE
       GENBANK/J01998
 AB    We have previously identified a residue in the carboxyl terminus of
       human immunodeficiency virus type 1 integrase (HIV-1 IN), W-235, the
       requirement for which is only revealed in viral assays for integrase
       function (P. M. Cannon, W. Wilson, E. Byles, S. M. Kingsman, and A. J.
       Kingsman, J. Virol. 68:4768-4775, 1994). Our further analysis of this
       region of retroviral IN has now identified several sequence motifs which
       are conserved in all the retroviruses we examined, apart from human
       spumaretrovirus. We have made mutations within these motifs in HIV-1 IN
       and examined their phenotypes when reintroduced into an infectious
       proviral clone. The deleterious effects of several of these mutations
       demonstrate the importance of these regions for IN function in vivo. We
       observed a further discrepancy, at a motif that is only conserved in the
       lentiviruses, in the ability of mutants to function in in vitro and in
       vivo assays. Substitutions both in this region and at W-235 abolish
       HIV-1 infectivity but do not affect particle production, morphology,
       reverse transcription, or nuclear import in T-cell lines. Taken together
       with the in vitro data suggesting that neither of these residues is
       directly involved in the catalytic reactions of IN, it seems likely that
       we have identified regions of IN that are essential for interactions
       with other components of the integration machinery.
 DE    Amino Acid Sequence  Animal  Base Sequence  Cell Line  *Conserved
       Sequence  DNA Nucleotidyltransferases/GENETICS/*METABOLISM  *DNA, Viral
       Human  HIV-1/*ENZYMOLOGY/PHYSIOLOGY  Molecular Sequence Data
       Mutagenesis  Support, Non-U.S. Gov't  Viral Proteins/METABOLISM  *Virus
       Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

