Chemotactic and inflammatory responses in the liver and brain are associated with pathogenesis of rift valley fever virus infection in the mouse

Kimberly K. Gray, Melissa N. Worthy, Terry L. Juelich, Stacy L. Agar, Allison Poussard, Dan Ragland, Alexander Freiberg, Michael R. Holbrook

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Rift Valley fever virus (RVFV) is a major human and animal pathogen associated with severe disease including hemorrhagic fever or encephalitis. RVFV is endemic to parts of Africa and the Arabian Peninsula, but there is significant concern regarding its introduction into non-endemic regions and the potentially devastating effect to livestock populations with concurrent infections of humans. To date, there is little detailed data directly comparing the host response to infection with wild-type or vaccine strains of RVFV and correlation with viral pathogenesis. Here we characterized clinical and systemic immune responses to infection with wild-type strain ZH501 or IND vaccine strain MP-12 in the C57BL/6 mouse. Animals infected with live-attenuated MP-12 survived productive viral infection with little evidence of clinical disease and minimal cytokine response in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion of lymphocytes and platelets and elicited a strong, systemic cytokine response which correlated with high virus titers and significant tissue pathology. Lymphopenia and platelet depletion were indicators of disease onset with indications of lymphocyte recovery correlating with increases in G-CSF production. RVFV is hepatotropic and in these studies significant clinical and histological data supported these findings; however, significant evidence of a pro-inflammatory response in the liver was not apparent. Rather, viral infection resulted in a chemokine response indicating infiltration of immunoreactive cells, such as neutrophils, which was supported by histological data. In brains of ZH501 infected mice, a significant chemokine and pro-inflammatory cytokine response was evident, but with little pathology indicating meningoencephalitis. These data suggest that RVFV pathogenesis in mice is associated with a loss of liver function due to liver necrosis and hepatitis yet the long-term course of disease for those that might survive the initial hepatitis is neurologic in nature which is supported by observations of human disease and the BALB/c mouse model.

Original languageEnglish (US)
Article numbere1529
JournalPLoS Neglected Tropical Diseases
Volume6
Issue number2
DOIs
StatePublished - Feb 2012

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Rift Valley fever virus
Virus Diseases
Liver
Brain
Cytokines
Infection
Chemokines
Hepatitis
Blood Platelets
Vaccines
Lymphocyte Depletion
Pathology
Lymphopenia
Meningoencephalitis
Livestock
Granulocyte Colony-Stimulating Factor
Encephalitis
Viral Load
Inbred C57BL Mouse
Nervous System

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Chemotactic and inflammatory responses in the liver and brain are associated with pathogenesis of rift valley fever virus infection in the mouse. / Gray, Kimberly K.; Worthy, Melissa N.; Juelich, Terry L.; Agar, Stacy L.; Poussard, Allison; Ragland, Dan; Freiberg, Alexander; Holbrook, Michael R.

In: PLoS Neglected Tropical Diseases, Vol. 6, No. 2, e1529, 02.2012.

Research output: Contribution to journalArticle

Gray, Kimberly K. ; Worthy, Melissa N. ; Juelich, Terry L. ; Agar, Stacy L. ; Poussard, Allison ; Ragland, Dan ; Freiberg, Alexander ; Holbrook, Michael R. / Chemotactic and inflammatory responses in the liver and brain are associated with pathogenesis of rift valley fever virus infection in the mouse. In: PLoS Neglected Tropical Diseases. 2012 ; Vol. 6, No. 2.
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