Visualizing the viral burden: phenotypic and functional alterations of T cells and APCs during persistent infection

Dirk Homann1, Dorian B McGavern, Michael B A Oldstone

  • 1Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, CA 92037, USA. dirk.homann@uchsc.edu

Insights

Persistent viral infections impact the immune system, infecting most immune cells. This study reveals specific infection patterns in lymphocytes and antigen-presenting cells (APCs) that alter immune responses, offering therapeutic insights.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Persistent viral infections pose significant public health challenges.
  • Chronic viral burden compromises immune cell function, particularly lymphocytes and antigen-presenting cells (APCs).
  • Understanding immune cell susceptibility and response is crucial for managing persistent infections.

Purpose of the Study:

  • To investigate the distribution and impact of persistent lymphocytic choriomeningitis virus (LCMV) infection on various immune cell subsets in vivo.
  • To analyze the functional consequences of viral infection on T cells and APCs.
  • To identify patterns of immune cell infection that correlate with altered immune responses.

Main Methods:

  • Utilized the lymphocytic choriomeningitis virus (LCMV) model in its natural murine host.
  • Employed direct ex vivo visualization techniques to identify and analyze virus-infected immune cells.
  • Compared functional parameters (activation, cytokine profiles, apoptosis) between infected and uninfected immune cell subsets.

Main Results:

  • LCMV infects a wide range of immune cells, with differential distribution among lymphocyte and APC subsets.
  • Immune cell infection patterns in blood reflect those in most organs and are independent of antibodies or complement.
  • LCMV-infected T cells exhibit heightened activation, skewed cytokine production, and increased apoptosis.
  • APCs show generalized activation, irrespective of viral antigen presence.

Conclusions:

  • Specific patterns of immune cell infection during persistent viral infections are linked to distinct immunostimulatory and immunosuppressive effects.
  • These findings provide insights into autoimmune processes associated with infections.
  • The study suggests potential therapeutic strategies for restoring immune function in persistent viral diseases.