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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding

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Ionic interaction of the HIV-1 V3 domain with CCR5 and deregulation of T lymphocyte function

Stavroula Baritaki1, Alexis Zafiropoulos, Maria Sioumpara

  • 1Department of Applied Biochemistry and Immunology, Institute of Molecular Biology and Biotechnology, Vassilika Vouton, Heraklion, Crete, Greece.

Biochemical and Biophysical Research Communications
|November 1, 2002
PubMed

Insights

The V3 region of HIV-1 gp120 triggers CD4+ T cell apoptosis, a process influenced by basic amino acids. This interaction with CCR5 involves specific molecular dynamics, offering insights into HIV-1 pathogenesis.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • The V3 region of HIV-1 gp120 is crucial for viral entry and interacts with host cell receptors.
  • Previous studies indicated that the V3 domain can induce apoptosis in CD4+ T lymphocytes, a key target of HIV-1 infection.
  • The mechanism by which this hypervariable region elicits a selective immune response remained unclear.

Purpose of the Study:

  • To investigate the molecular basis for the V3 region's ability to induce antigen-specific activation-induced cell death (AICD) in CD4+ T lymphocytes.
  • To determine the role of basic amino acids within the V3 peptide in mediating this interaction.
  • To elucidate the interaction between the V3 peptide and the CCR5 co-receptor.

Main Methods:

  • Synthesis and utilization of V3 peptides with varying numbers and positions of basic amino acids.
  • Assessment of T lymphocyte activation and apoptosis.
  • Surface plasmon resonance (SPR) biosensor analysis to study V3-CCR5 interactions.
  • Investigation of the role of tyrosine sulfation on CCR5.

Main Results:

  • The magnitude of T cell activation during V3-induced apoptosis was directly dependent on the number of basic amino acids in the V3 peptide.
  • Substitution of basic amino acids confirmed their critical role, while their position within the peptide was less important.
  • SPR analysis demonstrated that basic amino acids in V3 directly influence binding to the amino-terminal domain of CCR5.
  • Tyrosine sulfation of CCR5 was essential for this interaction.

Conclusions:

  • Simple molecular ionic interactions, specifically involving basic amino acids in the V3 peptide and CCR5, are capable of affecting key cellular events like T cell apoptosis.
  • These findings provide direct evidence for the role of specific amino acid properties in V3-mediated immune modulation.
  • The results support gp120 modeling predictions and highlight the need for further exploration of the broader biological implications of these molecular interactions in HIV-1 pathogenesis.

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