Seoul virus enhances regulatory and reduces proinflammatory responses in male Norway rats

Judith D. Easterbrook, Sabra L. Klein

Research output: Contribution to journalArticle

Abstract

Zoonotic pathogens, including hantaviruses, are maintained in the environment by causing persistent infection in the absence of disease in their reservoir hosts. Spillover of hantaviruses to humans can cause severe disease that is mediated by excessive proinflammatory responses. The mechanisms mediating hantaviral persistence in rodent reservoirs remain largely unknown. Male Norway rats were inoculated with their species-specific hantavirus, Seoul virus (SEOV), and viral RNA, cytokine, and chemokine responses were evaluated in spleen and lung tissue. More viral RNA was detectable in the lungs than spleen, with copies of SEOV peaking 15-30 days post-inoculation (p.i.) and persisting for 60 days p.i. In the lungs, the expression and production of proinflammatory mediators (i.e., IL-1β, IL-6, TNF-α, IFN-γ, CCL5, CCL2, CX3CL1, CXCL10, VCAM, VEGF, and NOS2) remained at or below baseline throughout SEOV infection; whereas, regulatory factors, including TGF-β and FoxP3 were elevated. Conversely, in the spleen, proinflammatory responses were induced while regulatory responses remained unchanged during infection. To determine whether reduced proinflammatory responses mediate hantavirus persistence in the lungs, male rats were administered rIL-1β or vehicle for 30 days during SEOV infection. SEOV persistence and shedding were not affected by IL-1β treatment. Proinflammatory responses were elevated in rIL-1β-treated rats, but remained within physiological levels, suggesting that supra-physiological concentrations may be necessary for viral clearance at the cost of causing disease. Elevated regulatory responses may suppress excessively high proinflammatory responses at a site of elevated SEOV replication to contribute to viral persistence and prevent proinflammatory-mediated disease in reservoir hosts.

Original languageEnglish (US)
Pages (from-to)1308-1318
Number of pages11
JournalJournal of Medical Virology
Volume80
Issue number7
DOIs
StatePublished - Jul 1 2008

Keywords

  • HFRS
  • IL-1β
  • Regulatory T cell
  • TGF-β
  • TNF
  • Zoonotic

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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