INTRAHOST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EVOLUTION IS RELATED TO LENGTH OF THE IMMUNOCOMPETENT PERIOD

被引:140
作者
LUKASHOV, VV [1 ]
KUIKEN, CL [1 ]
GOUDSMIT, J [1 ]
机构
[1] UNIV AMSTERDAM, ACAD MED CTR, HUMAN RETROVIRUS LAB, 1105 AZ AMSTERDAM, NETHERLANDS
关键词
D O I
10.1128/JVI.69.11.6911-6916.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 distance to nonsynonymous 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 (r(2) = 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.
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页码:6911 / 6916
页数:6
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