OX40 facilitates control of a persistent virus infection

PLoS Pathog. 2012 Sep;8(9):e1002913. doi: 10.1371/journal.ppat.1002913. Epub 2012 Sep 6.


During acute viral infections, clearance of the pathogen is followed by the contraction of the anti-viral T cell compartment. In contrast, T cell responses need to be maintained over a longer period of time during chronic viral infections in order to control viral replication and to avoid viral spreading. Much is known about inhibitory signals such as through PD-1 that limit T cell activity during chronic viral infection, but little is known about the stimulatory signals that allow maintenance of anti-viral T cells. Here, we show that the co-stimulatory molecule OX40 (CD134) is critically required in the context of persistent LCMV clone 13 infection. Anti-viral T cells express high levels of OX40 in the presence of their cognate antigen and T cells lacking the OX40 receptor fail to accumulate sufficiently. Moreover, the emergence of T cell dependent germinal center responses and LCMV-specific antibodies are severely impaired. Consequently, OX40-deficient mice fail to control LCMV clone 13 infection over time, highlighting the importance of this signaling pathway during persistent viral infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adaptive Immunity / genetics*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chlorocebus aethiops
  • Germinal Center / metabolism
  • Germinal Center / physiology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / prevention & control
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, OX40 / genetics
  • Receptors, OX40 / metabolism
  • Receptors, OX40 / physiology*
  • Vero Cells
  • Virus Diseases / genetics
  • Virus Diseases / immunology*
  • Virus Diseases / prevention & control*
  • Virus Latency / immunology
  • Virus Latency / physiology


  • Receptors, OX40
  • Tnfrsf4 protein, mouse