       Document 0534
 DOCN  M9630534
 TI    Naturally occurring accessory gene mutations lead to persistent human
       immunodeficiency virus type 1 infection of CD4-positive T cells.
 DT    9603
 AU    Kishi M; Zheng YH; Bahmani MK; Tokunaga K; Takahashi H; Kakinuma M; Lai
       PK; Nonoyama M; Luftig RB; Ikuta K; Section of Serology, Hokkaido
       University, Sapporo, Japan.
 SO    J Virol. 1995 Dec;69(12):7507-18. Unique Identifier : AIDSLINE
       MED/96078994
 AB    Proviral DNA from cells surviving severe but transient cytopathic
       effects, mediated by infection with recombinant human immunodeficiency
       virus type 1 (HIV-1) carrying a single gene mutation at vif, vpr, or
       vpu, was characterized by use of HIV-1-specific primer pairs in a
       two-step PCR. Deletion mutations were detected in a region that spanned
       the vif and vpr open reading frames. Cloning and sequencing of the
       amplified DNA from this region revealed frequent large deletions in a
       limited number of nucleotide positions. Analyses of the deletions
       suggested that (i) genetic recombination, (ii) template-primer slippage,
       and (iii) misalignment of the growing point during reverse transcription
       of the HIV-1 genome might be the mechanisms that generated the
       mutations. Apart from the large deletions, smaller deletions that gave
       frameshift mutations in vif and/or vpr prevailed. In addition, cells
       infected with a triple mutant defective in vif, vpr, and vpu did not
       show any cytopathic effect. Thus, mutations generating multiple
       accessory gene defects during HIV-1 replication correlate with viral
       persistence and loss of cytopathogenicity.
 DE    Base Sequence  Cell Line, Transformed  Comparative Study  CD4-Positive
       T-Lymphocytes/*VIROLOGY  Defective Viruses/*GENETICS/IMMUNOLOGY  DNA
       Primers  DNA, Viral/GENETICS  Frameshift Mutation  *Genes, vif  *Genes,
       vpr  *Genes, vpu  Genome, Viral  Human
       HIV-1/*GENETICS/PHYSIOLOGY/PATHOGENICITY  Kinetics  Molecular Sequence
       Data  *Mutation  Oligonucleotide Probes  Proviruses/GENETICS/IMMUNOLOGY
       Sequence Deletion  Support, Non-U.S. Gov't  T-Lymphocytes  Time Factors
       Virus Replication/*GENETICS  JOURNAL ARTICLE

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

