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Correlation between HIV sequence evolution, specific immune response and clinical outcome in vertically infected
E Halapi1, T Leitner, M Jansson
1Microbiology and Tumorbiology Centre, Karolinska Institute, Stockholm, Sweden.
AIDS (London, England)
|December 5, 1997
Summary
Sequence evolution in infants with HIV-1 differs based on disease progression. Faster progression shows shorter genetic distances and more synonymous substitutions, while slower progression reveals greater diversity due to immune pressure.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) infection in infants presents varied disease progression rates.
- Understanding the viral sequence evolution is crucial for predicting clinical outcomes.
Purpose of the Study:
- To investigate the relationship between HIV-1 sequence evolution and the rate of disease progression in infected infants.
- To analyze variability in the gp120 V3 region of HIV-1 in relation to clinical course.
Main Methods:
- Analysis of gp120 V3 region variability in HIV-1 infected children with slow vs. progressive disease.
- Cloning and sequencing of viral DNA from peripheral blood mononuclear cells at multiple timepoints from birth up to five years.
- Estimation of sequence variability using genetic distance and synonymous/non-synonymous nucleotide substitution ratios.
Main Results:
- Children with rapid disease progression exhibited shorter genetic distances and a predominance of synonymous substitutions.
- Children with slow disease progression showed a preferential accumulation of non-synonymous substitutions.
- A decreased synonymous/non-synonymous substitution ratio correlated with enhanced serum reactivity to autologous viral peptides.
Conclusions:
- HIV-1 sequence evolution patterns differ significantly between infants with varying disease progression rates.
- Slower disease progression is associated with the emergence of a more antigenically diverse viral population, likely driven by stronger immune pressure.