Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host

Judith D. Easterbrook, M. Christine Zink, Sabra L. Klein

Research output: Contribution to journalArticlepeer-review

Abstract

Hantaviruses are zoonotic pathogens that maintain a persistent infection in their reservoir hosts, yet the mechanisms mediating persistence remain unknown. Regulatory T cell responses cause persistent infection by suppressing proinflammatory and effector T cell activity; hantaviruses may exploit these responses to cause persistence. To test this hypothesis, male Norway rats were inoculated with Seoul virus and regulatory T cells were monitored during infection. Increased numbers of CD4+CD25+Forkhead box P3+ T cells and expression of Forkhead box P3 and TGF-β were observed in the lungs of male rats during persistent Seoul virus infection. To determine whether regulatory T cells modulate Seoul virus persistence, regulatory T cells were inactivated in male rats by using an anti-rat CD25 monoclonal antibody (NDS-63). Inactivation of regulatory T cells reduced the amount of Seoul virus RNA present in the lungs and the proportion of animals shedding viral RNA in saliva. Because regulatory T cells suppress proinflammatory-induced pathogenesis, pathologic observations in the lungs were evaluated during infection. Subclinical acute multifocal areas of hemorrhage and edema were noted in the lungs during infection; inactivation of regulatory T cells reduced the amount of pathologic foci. Expression of TNF was suppressed during the persistent phase of infection; inactivation of regulatory T cells eliminated the suppression of TNF. Taken together, these data suggest that regulatory T cells mediate Seoul virus persistence, possibly through elevated transcription and synthesis of TGF-β and suppression of TNF. These data provide evidence of regulatory T cell involvement in the persistence of a zoonotic pathogen in its natural reservoir host.

Original languageEnglish (US)
Pages (from-to)15502-15507
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number39
DOIs
StatePublished - Sep 25 2007

Keywords

  • CD25
  • Emerging infectious diseases
  • Forkhead box P3
  • Hantavirus
  • TGF-β

ASJC Scopus subject areas

  • General

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