Evaluation of the severe combined immunodeficient (SCID) mouse as an animal model for dengue viral infection.
Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood lymphocytes (hu-PBL) were evaluated as an animal model for demonstrating dengue (DEN) viral infection. Reconstituted mice (hu-PBL-SCID) that demonstrated successful engraftment by the presence of serum titers of human immunoglobulin (Ig) were inoculated intraperitoneally with DEN virus serotype 1 (DEN-1). Serial blood samples were taken postinoculation and assayed for virus in C6/36 cells. The identity of all viral isolates was confirmed by an immunofluorescence antibody assay using DEN-1 monoclonal antibody. A total of six experiments were performed using different procedures of reconstitution and infection, and in three of these experiments, DEN-1 virus was recovered from the hu-PBL-SCID mice. In the first successful experiment, DEN-1 virus was recovered on postinoculation day (PID) 24 from blood, spleen, thymus, and lung tissues of one of eight hu-PBL-SCID mice. A second group of eight hu-PBL-SCID mice were inoculated with human monocytes infected in vitro with DEN-1 virus. Virus was recovered from the blood of mice between PID 15 and 23, and from lung tissue of one of these mice. In a third experiment, seven SCID mice were treated initially with anti-asialo GM1 antibody to eliminate natural killer cells, and then were injected simultaneously with a mixture of hu-PBL and DEN-1 virus. Virus was demonstrated in the blood of one mouse on PID 38, and in another mouse on PID 8, 12, 20, 24, and 36.(ABSTRACT TRUNCATED AT 250 WORDS)
Wu
S J
SJ
Infectious Diseases Department, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
Hayes
C G
CG
Dubois
D R
DR
Windheuser
M G
MG
Kang
Y H
YH
Watts
D M
DM
Sieckmann
D G
DG
D000818:Animals; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology / Q000302:isolation & purification; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000276:immunology; D014766:Viremia / Q000276:immunology
D007074:Immunoglobulin G