Virus immunocapture provides evidence of CD8 lymphocyte-derived HIV-1 in vivo

Gareth J Hughes1, Samantha J Willey, Alexandra Cochrane

  • 1Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, UK. gareth.hughes@ed.ac.uk

Insights

This study shows that Human Immunodeficiency Virus type 1 (HIV-1) can be released from infected CD8 T cells, contributing significantly to viral load. Up to 15% of plasma HIV-1 may originate from these CD8 lymphocytes.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • CD8 T cells play a crucial role in immune responses.
  • The contribution of CD8 T cells to Human Immunodeficiency Virus type 1 (HIV-1) replication and pathogenesis is not fully understood.
  • Understanding viral reservoirs is key to managing HIV-1 infection.

Purpose of the Study:

  • To develop and validate a method for specifically capturing HIV-1 virions originating from CD8 T cells.
  • To quantify the proportion of plasma HIV-1 derived from CD8 lymphocytes in infected individuals.

Main Methods:

  • Developed a novel immunocapture assay utilizing antibodies against host-derived proteins (CD8, CD3, CD36) on viral envelopes.
  • Employed quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) to measure captured HIV-1 levels.
  • Utilized in vitro models with purified CD8 T cells and CD3+CD8- T cells to confirm assay specificity.

Main Results:

  • The in vitro model confirmed that CD8 incorporation into virions is specific to CD8 T cell infection.
  • Anti-CD8 immunocapture revealed that up to 15% (range 10-33%) of plasma HIV-1 in infected individuals originates from CD8 lymphocytes.
  • CD8-derived virus levels showed a strong correlation with plasma viral load.

Conclusions:

  • HIV-1-infected CD8 T cells are a significant source of circulating virus.
  • The substantial contribution of CD8 T cells to viral load may exacerbate immune dysfunction and accelerate AIDS progression.
  • These findings highlight CD8 T cells as a potential target for HIV-1 therapeutic strategies.
Abstract