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Selective pressures of human immunodeficiency virus type 1 (HIV-1) during pediatric infection

Elcio Leal1, Mario Janini, Ricardo S Diaz

  • 1Federal University of São Paulo, São Paulo, Brazil. e.leal@unifesp.br

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|August 28, 2007
PubMed

Insights

Pediatric HIV-1 infection shows similar viral selection pressures as in adults, despite differences in immune response. Key viral gene regions in env were identified for within-host and population-level adaptation.

Area of Science:

  • Virology
  • Immunology
  • Population Genetics

Background:

  • Pediatric HIV-1 infection exhibits distinct immune responses compared to adults, including slower viral load decline and delayed, narrower T-cell responses.
  • Previous research focused on cellular immune responses, with limited understanding of population-level consequences of these pediatric-specific immune dynamics.
  • Investigating viral evolution in pediatric HIV-1 is crucial for understanding disease progression and transmission.

Purpose of the Study:

  • To analyze the selective pressures on HIV-1 genes (gag, pol, env) in pediatric infection.
  • To compare the intensity and distribution of selection in pediatric versus adult HIV-1 infections.
  • To identify specific viral gene regions with adaptive functions in pediatric HIV-1.

Main Methods:

  • Estimation of nonsynonymous (dN) and synonymous (dS) substitutions per codon using maximum likelihood and modified counting methods.
  • Analysis of selection intensity (dN/dS ratio) and identification of positively selected sites across HIV-1 genes.
  • Phylogenetic analysis to pinpoint adaptive regions within the HIV-1 env gene.

Main Results:

  • Both dN/dS ratio and the distribution/location of positively selected sites were similar between pediatric and adult HIV-1 infections, indicating comparable selection intensity and breadth.
  • Phylogenetic analysis revealed two distinct adaptive regions in the HIV-1 env gene.
  • One env region near the V3 loop may enhance within-host fitness during immune attack, while another (amino acids 334-368 of Gp160) may improve population-level transmission.

Conclusions:

  • The selective regimen driving HIV-1 evolution in children is as broad and intense as in adults, despite differing immune responses.
  • Specific regions in the HIV-1 env gene play critical roles in viral adaptation, influencing both within-host survival and inter-host transmission.
  • These findings offer insights into the evolutionary dynamics of pediatric HIV-1 and potential targets for therapeutic strategies.

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