Interferon α/β Receptor-Deficient Mice as a Model for Ebola Virus Disease.
A major obstacle in ebolavirus research is the lack of a small-animal model for Sudan virus (SUDV), as well as other wild-type (WT) ebolaviruses. Here, we expand on research by Bray and by Lever et al suggesting that WT ebolaviruses are pathogenic in mice deficient for the type 1 interferon (IFN) α/β receptor (IFNα/βR-/-). We examined the disease course of several WT ebolaviruses: Boneface (SUDV/Bon) and Gulu variants of SUDV, Ebola virus (EBOV), Bundibugyo virus (BDBV), Taï Forest virus, and Reston virus (RESTV). We determined that exposure to WT SUDV or EBOV results in reproducible signs of disease in IFNα/βR-/- mice, as measured by weight loss and partial lethality. Vaccination with the SUDV or EBOV glycoprotein (GP)-expressing Venezuelan equine encephalitis viral replicon particle vaccine protected these mice from SUDV/Bon and EBOV challenge, respectively. Treatment with SUDV- or EBOV-specific anti-GP antibodies protected mice from challenge when delivered 1-3 days after infection. Serial sampling experiments revealed evidence of disseminated intravascular coagulation in the livers of mice infected with the Boneface variant of SUDV, EBOV, and BDBV. Taken together, these data solidify the IFNα/βR-/- mouse as an important and useful model for the study of WT EBOV disease.
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
Jennifer M
JM
Brannan
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
Jeffery W
JW
Froude
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
Laura I
LI
Prugar
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
Russell R
RR
Bakken
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
Samantha E
SE
Zak
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
Sharon P
SP
Daye
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
Catherine E
CE
Wilhelmsen
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
John M
JM
Dye
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D046129:Ebola Vaccines / Q000276:immunology; D029043:Ebolavirus / Q000378:metabolism / Q000472:pathogenicity*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D019142:Hemorrhagic Fever, Ebola / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency*; D012093:Replicon / Q000276:immunology; D014611:Vaccination / Q000379:methods; D014709:Vero Cells / Q000821:virology; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism; D014774:Virulence / Q000276:immunology / Q000502:physiology*
D000914:Antibodies, Viral; D046129:Ebola Vaccines; D006023:Glycoproteins; D014764:Viral Proteins; D053633:Receptor, Interferon alpha-beta
Ebola virus; Ebola virus disease; Sudan virus; coagulopathy; mouse model; pathogenesis