       Document 1036
 DOCN  M9621036
 TI    Single basic amino acid substitutions at position 302 or 320 in the V3
       domain of HIV type 1 are not sufficient to alter the antiviral activity
       of dextran sulfate and heparin.
 DT    9602
 AU    Okada T; Gurney ME; Department of Cell, Molecular, and Structural
       Biology,; Northwestern University Medical School, Chicago, Illinois
       60611,; USA.
 SO    AIDS Res Hum Retroviruses. 1995 May;11(5):571-5. Unique Identifier :
       AIDSLINE MED/96093892
 AB    The third variable domain (V3 domain) of the human immunodeficiency
       virus type 1 (HIV-1) envelope glycoprotein gp120 contains a substantial
       number of positively charged amino acid residues. We previously
       demonstrated that mutation of basic amino acid residues at position 303,
       306, 309, 313, and 325 in the V3 domain of HIV-1 strain NL4-3 resulted
       in a dramatic elimination of both virus infectivity and
       syncytium-inducing ability. Mutations of arginine at position 302 to
       serine (R302S) or lysine at position 320 to glutamine (K320Q) had
       variable effects on infectivity for a panel of T cell lines tested.
       These mutations are located on opposite sides of the Gly-Pro-Gly-Arg-Ala
       sequence in the center of the V3 domain. The R302S and K320Q mutations
       allowed us to determine if these basic residues are important for virus
       neutralization by polyanionic compounds. Dextran sulfate and heparin
       inhibited the cytopathogenicities of both mutants for MT-4 cells,
       although their 50% antiviral effective doses were slightly higher than
       those required to achieve complete protection against wild-type
       HIV-1NL4-3 replication. This result emphasizes that the basic amino
       acids of Arg302 and Lys320 are not essential for the inhibitory effect
       of dextran sulfate and heparin on HIV-1 infection.
 DE    Amino Acid Sequence  Antiviral Agents/*PHARMACOLOGY  Arginine/GENETICS
       Base Sequence  Cell Line  Dextran Sulfate/*PHARMACOLOGY  DNA Primers
       Electrochemistry  Glutamine/GENETICS  Heparin/*PHARMACOLOGY  Human  HIV
       Envelope Protein gp120/CHEMISTRY/*DRUG EFFECTS/GENETICS  HIV-1/*DRUG
       EFFECTS/GENETICS  Lysine/GENETICS  Molecular Sequence Data  Mutagenesis,
       Site-Directed  Peptide Fragments/CHEMISTRY/*DRUG EFFECTS/GENETICS
       Serine/GENETICS  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       JOURNAL ARTICLE

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

