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Variability and immunogenicity of human immunodeficiency virus type 1 p24 gene quasispecies

J Iroegbu1, M Birk, U Lazdina

  • 1Divisions of Clinical Virology, F68, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden.

Clinical and Diagnostic Laboratory Immunology
|May 9, 2000
PubMed

Insights

Human immunodeficiency virus type 1 (HIV-1) p24 gene evolution shows host-specific changes, but limited genetic variability (<1%) minimally impacts immune responses. This suggests host genetics, not minor viral variations, primarily shape immunity to HIV-1.

Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • Human immunodeficiency virus type 1 (HIV-1) gag gene is conserved, yet diverse p24 gene quasispecies exist within infected patients.
  • Understanding HIV-1 p24 gene evolution and its impact on host immune response is crucial for vaccine development.

Purpose of the Study:

  • To investigate the genetic variability of the HIV-1 p24 gene within and between patients.
  • To assess the influence of host genetics, specifically major histocompatibility complex (MHC), on immune responses to HIV-1 p24.
  • To determine the impact of minor genetic variations in p24 on immunogenicity.

Main Methods:

  • Cloning and sequencing of 31 p24 genes from four HIV-1-infected patients.
  • Analysis of intrapatient and interpatient homology.
  • Design of DNA-based immunogens from distinct p24 quasispecies for plasmid immunization in mice with different MHC haplotypes (H-2b, H-2d, H-2k).

Main Results:

  • High intrapatient homology (97.1-99.1%) and lower interpatient homology (91.5-93.8%) suggest host-specific HIV-1 evolution.
  • Synonymous and nonsynonymous nucleotide changes were evenly distributed, with minimal influence from host cytotoxic T-cell response sites.
  • Host MHC haplotype significantly influenced immune responses to p24 DNA immunogens, while limited genetic variability (<1%) did not affect immunogenicity.

Conclusions:

  • HIV-1 p24 evolution is influenced by host-specific factors, but minor genetic variations (<1%) have minimal impact on immune responses.
  • Host major histocompatibility complex plays a significant role in shaping the immune response to HIV-1 p24.
  • These findings have implications for understanding HIV-1 persistence and designing effective immunotherapies or vaccines.

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