Chikungunya virus impairs draining lymph node function by inhibiting HEV-mediated lymphocyte recruitment

JCI Insight. 2018 Jul 12;3(13):e121100. doi: 10.1172/jci.insight.121100.


Chikungunya virus (CHIKV) causes acute and chronic rheumatologic disease. Pathogenic CHIKV strains persist in joints of immunocompetent mice, while the attenuated CHIKV strain 181/25 is cleared by adaptive immunity. We analyzed the draining lymph node (dLN) to define events in lymphoid tissue that may contribute to CHIKV persistence or clearance. Acute 181/25 infection resulted in dLN enlargement and germinal center (GC) formation, while the dLN of mice infected with pathogenic CHIKV became highly disorganized and depleted of lymphocytes. Using CHIKV strains encoding ovalbumin-specific TCR epitopes, we found that lymphocyte depletion was not due to impaired lymphocyte proliferation. Instead, the accumulation of naive lymphocytes transferred from the vasculature to the dLN was reduced, which was associated with fewer high endothelial venule cells and decreased CCL21 production. Following NP-OVA immunization, NP-specific GC B cells in the dLN were decreased during pathogenic, but not attenuated, CHIKV infection. Our data suggest that pathogenic, persistent strains of CHIKV disable the development of adaptive immune responses within the dLN.

Keywords: Immunology; Infectious disease; Lymph.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptive Immunity*
  • Animals
  • B-Lymphocytes
  • Cell Proliferation
  • Chemokine CCL21
  • Chikungunya Fever / immunology*
  • Chikungunya Fever / virology
  • Chikungunya virus / pathogenicity*
  • Disease Models, Animal
  • Epitopes
  • Immunization
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology
  • Lymph Nodes / virology
  • Lymphocyte Activation
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / pathology
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin
  • Stromal Cells / immunology
  • Venules


  • Chemokine CCL21
  • Epitopes
  • Ovalbumin