Recombinant Eimeria protozoan protein elicits resistance to acute phlebovirus infection in mice but not hamsters.
A protein antigen from an Eimeria protozoan has recently been reported to induce antitumor activity in mice. This activity most likely results from the strong induction of interkeukin-12 (IL-12) and gamma interferon (IFN-gamma), which are also essential factors in the establishment of protective immunity against viral infection. We evaluated recombinant Eimeria antigen (rEA) as a potential immunotherapeutic agent in mouse and hamster models of acute phleboviral disease. Punta Toro virus (PTV) was highly sensitive to a single dose of nanogram quantities of rEA in the mouse infection model. Intraperitoneal treatment with rEA also reduced virus load and liver damage associated with PTV infection. IL-12 was elicited following exposure of uninfected mice to quantities of rEA of 10 ng or greater, and the levels peaked at between 3 and 8 h postexposure. IFN-gamma release was induced more slowly and required less rEA (1 ng) to produce a significant rise in systemic levels. The induction of IL-12 and IFN-gamma involved in the coordination of innate and adaptive immune responses to microbial pathogens required myeloid differentiation factor 88, a signaling adaptor shared by most members of the Toll-like receptor (TLR) family. Despite encouraging results in the murine system, rEA failed to protect hamsters challenged with PTV. Our findings suggest that hamsters may lack functional TLR11, which has recently been shown to recognize a profilin-like protein homologous to rEA from the protozoan Toxoplasma gondii. Further investigation into the immunostimulatory capacity of rEA in other mammalian systems is necessary.
Gowen
Brian B
BB
Institute for Antiviral Research, Utah State University, Logan, 84322, USA. bgowen@cc.usu.edu
Smee
Donald F
DF
Wong
Min-Hui
MH
Judge
John W
JW
Jung
Kie-Hoon
KH
Bailey
Kevin W
KW
Pace
Anne M
AM
Rosenberg
Barnett
B
Sidwell
Robert W
RW
D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000818:Animals; D002044:Bunyaviridae Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D002478:Cells, Cultured; D006224:Cricetinae; D004306:Dose-Response Relationship, Immunologic; D004539:Eimeria / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88; D016856:Phlebovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D016019:Survival Analysis; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D019562:Viral Load
D048868:Adaptor Proteins, Signal Transducing; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D051196:Toll-Like Receptor 3; D018664:Interleukin-12; D007371:Interferon-gamma