       Document 0395
 DOCN  M9620395
 TI    Intrahost human immunodeficiency virus type 1 evolution is related to
       length of the immunocompetent period.
 DT    9602
 AU    Lukashov VV; Kuiken CL; Goudsmit J; Human Retrovirus Laboratory,
       University of Amsterdam, The; Netherlands.
 SO    J Virol. 1995 Nov;69(11):6911-6. Unique Identifier : AIDSLINE
       MED/96013791
 AB    The antigenic diversity threshold theory predicts that antigenic sites
       of human immunodeficiency virus type 1, such as the V3 region of the
       external glycoprotein gp120, evolve more rapidly during the symptom-free
       period in individuals progressing to AIDS than in those who remain
       asymptomatic for a long time. To test this hypothesis, genomic RNA
       sequences were obtained from the sera of 44 individuals at
       seroconversion and 5 years later. The mean number of nonsynonymous
       nucleotide substitutions in the V3 region of the viruses circulating in
       31 nonprogressors (1.1 x 10(-2) +/- 0.1 x 10(-2) per site per year) was
       higher than the corresponding value for 13 progressors (0.66 x 10(-2)
       +/- 0.1 x 10(-2) per site per year) (P < 0.01), while no difference
       between the mean numbers of synonymous substitutions in the two groups
       was seen (0.37 x 10(-2) +/- 0.1 x 10(-2) and 0.51 x 10(-2) +/- 0.2 x
       10(-2) per site per year for nonprogressors and progressors,
       respectively; P > 0.1). The mean ratios of synonymous nucleotide p
       distance to nonsynonymous p distance were 0.35 for nonprogressors and
       0.62 for progressors. The number of nonsynonymous substitutions was not
       associated with virus load or virus phenotype, which are established
       predictors of disease progression, but correlated strongly with the
       duration of the immunocompetent period (r2 = 0.41; P = 0.001). This
       indicates that there is no causative relationship between intrahost
       evolution and CD4+ cell decline. Our data suggest that intrahost
       evolution in human immunodeficiency virus type 1 infection is driven by
       selective forces, the strength of which is related to the duration of
       the immunocompetent period.
 DE    Acquired Immunodeficiency Syndrome/*IMMUNOLOGY  *Antigenic Variation
       Cohort Studies  Disease Progression  *Evolution  Homosexuality, Male
       Human  HIV Envelope Protein gp120/*GENETICS  HIV
       Seropositivity/*IMMUNOLOGY  HIV-1/*GENETICS/IMMUNOLOGY
       *Immunocompetence  Male  Phenotype  Phylogeny  Prospective Studies
       Support, Non-U.S. Gov't  Time Factors  JOURNAL ARTICLE

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

