Ebola Virus Replication and Disease Without Immunopathology in Mice Expressing Transgenes to Support Human Myeloid and Lymphoid Cell Engraftment.
The study of Ebola virus (EBOV) pathogenesis in vivo has been limited to nonhuman primate models or use of an adapted virus to cause disease in rodent models. Herein we describe wild-type EBOV (Makona variant) infection of mice engrafted with human hematopoietic CD34+stem cells (Hu-NSG™-SGM3 mice; hereafter referred to as SGM3 HuMice). SGM3 HuMice support increased development of myeloid immune cells, which are primary EBOV targets. In SGM3 HuMice, EBOV replicated to high levels, and disease was observed following either intraperitoneal or intramuscular inoculation. Despite the high levels of viral antigen and inflammatory cell infiltration in the liver, the characteristic histopathology of Ebola virus disease was not observed, and this absence of severe immunopathology may have contributed to the recovery and survival of some of the animals. Future investigations into the underlying mechanisms of the atypical disease presentation in SGM3 HuMice will provide additional insights into the immunopathogenesis of severe EBOV disease.
Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia.
Jessica R
JR
Spengler
Laboratory of Persistent Viral Diseases.
Kerry J
KJ
Lavender
Laboratory of Virology.
Cynthia
C
Martellaro
Research Technologies Branch.
Aaron
A
Carmody
Center for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
Andreas
A
Kurth
In Vivo Services, The Jackson Laboratory, Sacramento, California.
James G
JG
Keck
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana.
Greg
G
Saturday
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana.
Dana P
DP
Scott
Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia.
Stuart T
ST
Nichol
Laboratory of Persistent Viral Diseases.
Kim J
KJ
Hasenkrug
Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia.
Christina F
CF
Spiropoulou
Laboratory of Virology.
Heinz
H
Feldmann
Laboratory of Virology.
Joseph
J
Prescott
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008214:Lymphocytes / Q000473:pathology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology; D019076:Transgenes; D014779:Virus Replication
D000956:Antigens, Viral
Ebola; flow cytometry; hemorrhagic fever; humanized NSG-SGM3 mice; immune response; immunopathology; myeloid cell; virus