Lethal Monkeypox Virus Infection of CAST/EiJ Mice Is Associated with a Deficient Gamma Interferon Response
- 1 September 2012
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 86 (17), 9105-9112
- https://doi.org/10.1128/jvi.00162-12
Abstract
Monkeypox virus (MPXV) is endemic in Africa, where it causes disease in humans resembling smallpox. A recent importation of MPXV-infected animals into the United States raises the possibility of global spread. Rodents comprise the major reservoir of MPXV, and a variety of such animals, even those native to North America, are susceptible. In contrast, common inbred strains of mice, including BALB/c and C57BL/6, are greatly resistant to MPXV. However, several inbred strains of mice derived from wild mice, including CAST/EiJ, exhibit morbidity and mortality at relatively low inoculums of MPXV. Elucidating the basis for the susceptibility of CAST/EiJ mice could contribute to an understanding of MPXV pathogenicity and host defense mechanisms and enhance the value of this mouse strain as a model system for evaluation of therapeutics and vaccines. Here we compared virus dissemination and induced cytokine production in CAST/EiJ mice to those in the resistant BALB/c strain. Following intranasal infection, robust virus replication occurred in the lungs of both strains, although a relatively higher inoculum was required for BALB/c. However, while spread to other internal organs was rapid and efficient in CAST/EiJ mice, the virus was largely restricted to the lungs in BALB/c mice. Gamma interferon (IFN-γ) and CCL5 were induced in lungs of BALB/c mice concomitant with virus replication but not in CAST/EiJ mice. The importance of IFN-γ in protection against MPXV disease was demonstrated by the intranasal administration of the mouse cytokine to CAST/EiJ mice and the resulting protection against MPXV. Furthermore, C57BL/6 mice with inactivation of the IFN-γ gene or the IFN-γ receptor gene exhibited enhanced sensitivity to MPXV.Keywords
This publication has 49 references indexed in Scilit:
- Comparative Analysis of Monkeypox Virus Infection of Cynomolgus Macaques by the Intravenous or Intrabronchial Inoculation RouteJournal of Virology, 2011
- Using Remote Sensing to Map the Risk of Human Monkeypox Virus in the Congo BasinEcohealth, 2010
- Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of CongoProceedings of the National Academy of Sciences of the United States of America, 2010
- Identification of Wild-Derived Inbred Mouse Strains Highly Susceptible to Monkeypox Virus Infection for Use as Small Animal ModelsJournal of Virology, 2010
- Experimental infection of an African dormouse (Graphiurus kelleni) with monkeypox virusVirology, 2009
- Monkeypox virus and insights into its immunomodulatory proteinsImmunological Reviews, 2008
- Monkeypox-Induced Immunity and Failure of Childhood Smallpox Vaccination To Provide Complete ProtectionClinical and Vaccine Immunology, 2007
- Poxvirus-Encoded Gamma Interferon Binding Protein Dampens the Host Immune Response to InfectionJournal of Virology, 2007
- Protective Immunity against Secondary Poxvirus Infection Is Dependent on Antibody but Not on CD4 or CD8 T-Cell FunctionJournal of Virology, 2006
- Host Genetics of Bordetella pertussis Infection in Mice: Significance of Toll-Like Receptor 4 in Genetic Susceptibility and PathobiologyInfection and Immunity, 2006