Document 0539
 DOCN  M9460539
 TI    Fidelity of HIV-1 reverse transcriptase copying a hypervariable region
       of the HIV-1 env gene.
 DT    9404
 AU    Ji J; Loeb LA; Joseph Gottstein Memorial Cancer Research Laboratory,
       Department; of Pathology, University of Washington, Seattle 98195.
 SO    Virology. 1994 Mar;199(2):323-30. Unique Identifier : AIDSLINE
       MED/94167866
 AB    The unusually high mutation frequency exhibited by the human
       immunodeficiency virus (HIV) is a major impediment to developing
       effective vaccines against the virus and to designing analogs that
       inhibit viral replication. To investigate the molecular basis of HIV
       hypermutability, we established cell-free assays to measure the fidelity
       of HIV-1 reverse transcriptase (RT) in copying either DNA or both RNA
       and DNA templates that contain the hypervariable region 1 of the HIV-1
       env gene (V-1). The fidelity of DNA synthesis was measured by
       repetitively copying the envelope gene (V-1) DNA by HIV-1 RT, followed
       by cloning and sequencing these newly synthesized DNA products. We found
       that the error rate of HIV RT copying either RNA or DNA of the env V-1
       region is about one misincorporation per 5 kb polymerized. This rate is
       similar to that found with the M13mp2 forward mutation assay using the
       lacZ alpha gene as a template. This similarity suggests that the HIV env
       hypervariable sequence is not inherently hypermutable. The high error
       rate of HIV RT suggests that misincorporation by this enzyme is a major
       source of mutations throughout the viral genome and a determinant for
       rapid viral evolution. The spectrum of mutations produced by HIV RT in
       vitro partially correlates with the spectrum of HIV mutations observed
       in AIDS patients. The differences between these spectra highlight the
       contribution of phenotypic selection during HIV-1 infection. The overall
       uniformity of misincorporation of HIV-1 RT further suggests an
       alternative anti-HIV strategy based on increasing viral mutagenesis by
       nucleotide analogs.
 DE    Base Sequence  DNA, Viral/GENETICS  Genes, env/*GENETICS
       HIV-1/*GENETICS  Molecular Sequence Data  Mutation/*GENETICS  Reverse
       Transcriptase/GENETICS/*PHYSIOLOGY  RNA, Viral/GENETICS  Support, U.S.
       Gov't, P.H.S.  Templates  JOURNAL ARTICLE

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