       Document 0113
 DOCN  M9630113
 TI    Domains of the human immunodeficiency virus type 1 matrix and gp41
       cytoplasmic tail required for envelope incorporation into virions.
 DT    9603
 AU    Freed EO; Martin MA; Laboratory of Molecular Microbiology, National
       Institute of; Allergy and Infectious Diseases, Bethesda, Maryland
       20892-0460,; USA.
 SO    J Virol. 1996 Jan;70(1):341-51. Unique Identifier : AIDSLINE
       MED/96099449
 AB    We recently demonstrated that a single amino acid substitution in matrix
       residue 12 (12LE) or 30 (30LE) blocks the incorporation of human
       immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into
       virions and that this block can be reversed by pseudotyping with
       heterologous retroviral envelope glycoproteins with short cytoplasmic
       tails or by truncating the cytoplasmic tail of HIV-1 transmembrane
       glycoprotein gp41 by 104 or 144 amino acids. In this study, we mapped
       the domain of the gp41 cytoplasmic tail responsible for the block to
       incorporation into virions by introducing a series of eight truncation
       mutations that eliminated 23 to 93 amino acids from the C terminus of
       gp41. We found that incorporation into virions of a HIV-1 envelope
       glycoprotein with a deletion of 23, 30, 51, or 56 residues from the C
       terminus of gp41 is specifically blocked by the 12LE matrix mutation,
       whereas truncations of greater than 93 amino acids reverse this defect.
       To elucidate the role of matrix residue 12 in this process, we
       introduced a number of additional single amino acid substitutions at
       matrix positions 12 and 13. Charged substitutions at residue 12 blocked
       envelope incorporation and virus infectivity, whereas more subtle amino
       acid substitutions resulted in a spectrum of envelope incorporation
       defects. To characterize further the role of matrix in envelope
       incorporation into virions, we obtained and analyzed second-site
       revertants to two different matrix residue 12 mutations. A Val-->Ile
       substition at matrix amino acid 34 compensated for the effects of both
       amino acid 12 mutations, suggesting that matrix residues 12 and 34
       interact during the incorporation of HIV-1 envelope glycoproteins into
       nascent virions.
 DE    Amino Acid Sequence  Base Sequence  Binding Sites  Cell Line  DNA, Viral
       Gene Products, env/METABOLISM  Gene Products, gag/CHEMISTRY/*METABOLISM
       Hela Cells  Human  HIV Antigens/CHEMISTRY/*METABOLISM  HIV Envelope
       Protein gp41/CHEMISTRY/*METABOLISM  HIV-1/*METABOLISM  Molecular
       Sequence Data  Mutagenesis  Mutation  Protein Precursors/METABOLISM
       Viral Envelope Proteins/*METABOLISM  Virion/METABOLISM  JOURNAL ARTICLE

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

