Document 3284
 DOCN  M94A3284
 TI    A computer simulator generating nucleotide sequence variation of the
       HIV-1 genome.
 DT    9412
 AU    Doi H; Fujitsu Labs. Ltd., Chiba, Japan.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):111 (abstract no. PA0063). Unique
       Identifier : AIDSLINE ICA10/94369291
 AB    OBJECTIVE: To know the range of nucleotide sequence variation of the
       HIV-1 genome, in particular, of the variable regions. It has been
       assumed that in most cases HIV-1 infection is initiated by a single
       infectious virion. However, no one knows the range of variation within a
       patient after infection. I therefore made a computer simulator to
       generate the sequence variation. SIMULATOR: The HIV-1 reverse
       transcriptase (RT) might interact with 6 to 7 bp long stretch of RNA-DNA
       hybrid or double stranded DNA at the polymerase site during DNA
       synthesis (Jacobo-Molina, A. et al., Proc. Natl. Acad. Sci. USA, 1993,
       90, 6320; Arnold, E. et al., Nature, 1992, 357, 85; Kohlstaedt, L.A. et
       al., Science, 1992, 256, 1783). 6-mers of purine-pyrmidine content have
       been shown to be important for evolution of HIV-1 (Doi, H., Proc. Natl.
       Acad. Sci. USA, 1991, 88, 9282). Therefore, the error spectra of 6-mers,
       in which the transition probability to other nucleotides at a site of
       the 6-mer is a value between 0.1 to 1.0, were obtained from the
       nucleotide sequences of the strains entire sequences of which are known.
       They might reflect the error-proneness of the HIV-1 RT, because of the
       strategic codon frame in env, gag and pol. In the simulator, they were
       composed along the nucleotide sequence tested, and nucleotide
       substitution for another one at each site of the tested sequence was
       stochastically determined according to the composed transition
       probability; and then various sequences were stochastically generated.
       RESULTS, DISCUSSION AND CONCLUSIONS: The computer simulator showed
       ranges of nucleotide sequence variation of V1-5 and other regions. A
       variable region was found in vpu by simulation, but the region was
       conservative in isolated viruses. This suggest that the simulator can
       search a region where is highly variable during reverse transcription
       but on which a strong selection pressure might act.
 DE    *Computer Simulation  DNA, Viral/GENETICS/METABOLISM  Genes, env  Genes,
       gag  Genes, pol  Genes, vpu  *Genome, Viral  Human  HIV
       Infections/MICROBIOLOGY  HIV-1/ENZYMOLOGY/*GENETICS  *Models, Genetic
       Reverse Transcriptase/METABOLISM  *Variation (Genetics)  MEETING
       ABSTRACT

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