Contribution of human lung parenchyma and leukocyte influx to oxidative stress and immune systemmediated pathology following Nipah virus infection

Olivier Escaffre, Tais Saito, Terry L. Juelich, Tetsuro Ikegami, Jennifer K. Smith, David D. Perez, Colm Atkins, Corri B. Levine, Matthew Huante, Rebecca J. Nusbaum, Janice Endsley, Alexander Freiberg, Barry Rockx

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD-SCID/γ mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the bone marrow, liver, and thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections. Here, we characterized NiV Bangladesh strain (NiV-B) infection of human lung grafts from human immune systemreconstituted mice in order to identify the overall effect of immune cells on NiV pathogenesis of the lung. We show that NiV-B replicated to high titers in human lung grafts and caused similar cytopathic effects irrespective of the presence of human leukocytes in mice. However, the human immune system interfered with virus spread across lung grafts, responded to infection by leukocyte migration to small airways and alveoli of the lung grafts, and accelerated oxidative stress in lung grafts. In addition, the presence of human leukocytes increased the expression of cytokines and chemokines that regulate inflammatory influx to sites of infection and tissue damage. These results advance our understanding of how the immune system limits NiV dissemination and contributes to ALI and inform efforts to identify therapeutic targets.

Original languageEnglish (US)
Article numbere00275-17
JournalJournal of Virology
Volume91
Issue number15
DOIs
StatePublished - Aug 1 2017

Keywords

  • Antioxidant therapies
  • Henipavirus
  • Human lung grafts
  • Humanized mouse
  • Inflammatory response
  • Oxidative stress
  • Virus replication

ASJC Scopus subject areas

  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'Contribution of human lung parenchyma and leukocyte influx to oxidative stress and immune systemmediated pathology following Nipah virus infection'. Together they form a unique fingerprint.

  • Cite this