Andes and Prospect Hill hantaviruses differ in early induction of interferon although both can downregulate interferon signaling

Christina F. Spiropoulou, César G. Albariño, Thomas Ksiazek, Pierre E. Rollin

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease which is thought to result from a dysregulated immune response to infection with pathogenic hantaviruses, such as Sin Nombre virus or Andes virus (ANDV). Other New World hantaviruses, such as Prospect Hill virus (PHV), have not been associated with human disease. Activation of an antiviral state and cell signaling in response to hantavirus infection were examined using human primary lung endothelial cells, the main target cell infected in HPS patients. PHV, but not ANDV, was found to induce a robust beta interferon (IFN-β) response early after infection of primary lung endothelial cells. The level of IFN induction correlated with IFN regulatory factor 3 (IRF-3) activation, in that IRF-3 dimerization and nuclear translocation were detected in PHV but not ANDV infection. In addition, phosphorylated Stat-1/2 levels were significantly lower in the ANDV-infected cells relative to PHV. Presumably, this reflects the lower level of IRF-3 activation and initial IFN induced by ANDV relative to PHV. To determine whether, in addition, ANDV interference with IFN signaling also contributed to the low Stat-1/2 activation seen in ANDV infection, the levels of exogenous IFN-βinduced Stat-1/2 activation detectable in uninfected versus ANDV- or PHV-infected Vero-E6 cells were examined. Surprisingly, both viruses were found to downregalate IFN-induced Stat-1/2 activation. Analysis of cells transiently expressing only ANDV or PHV glycoproteins implicated these proteins in this downregulation. In conclusion, while both viruses can interfere with IFN signaling, there is a major difference in the initial interferon induction via IRF-3 activation between ANDV and PHV in infected primary endothelial cells, and this correlates with the reported differences in pathogenicity of these viruses.

Original languageEnglish (US)
Pages (from-to)2769-2776
Number of pages8
JournalJournal of Virology
Volume81
Issue number6
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Hantavirus
interferons
Interferons
Down-Regulation
viruses
Viruses
Interferon Regulatory Factor-3
Sin Nombre virus
Hantavirus Pulmonary Syndrome
endothelial cells
infection
Endothelial Cells
Virus Diseases
cells
lungs
Andes virus
Hantavirus Infections
interferon-beta
dimerization
Lung

ASJC Scopus subject areas

  • Immunology

Cite this

Andes and Prospect Hill hantaviruses differ in early induction of interferon although both can downregulate interferon signaling. / Spiropoulou, Christina F.; Albariño, César G.; Ksiazek, Thomas; Rollin, Pierre E.

In: Journal of Virology, Vol. 81, No. 6, 03.2007, p. 2769-2776.

Research output: Contribution to journalArticle

Spiropoulou, Christina F. ; Albariño, César G. ; Ksiazek, Thomas ; Rollin, Pierre E. / Andes and Prospect Hill hantaviruses differ in early induction of interferon although both can downregulate interferon signaling. In: Journal of Virology. 2007 ; Vol. 81, No. 6. pp. 2769-2776.
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