Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype.
We aimed to evaluate the efficacy of VSV-G pseudotyped, defective HIV-1 based lentiviral vectors for the neonatal transfer of therapeutic genes following systemic administration in Sandhoff mouse pups. Despite transgene expression in mouse brains, these animals presented with significant exacerbation and acceleration of the disease neurological phenotype. We observed an increase and acceleration in the presence of MHC-II and CD45+ cells in their brains, along with neuroinflammation, but not in control heterozygous or wild type littermates that also received the same treatment.
Kyrkanides
Stephanos
S
Eastman Dental Center, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United States. stephanos_kyrkanides@urmc.rochester.edu <stephanos_kyrkanides@urmc.rochester.edu>
Miller
Jen-nie H
JN
Tallents
Ross H
RH
Brouxhon
Sabine M
SM
Centola
Gina M
GM
Olschowka
John A
JA
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology* / Q000821:virology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018398:Homeodomain Proteins; D007274:Injections, Intraperitoneal; D016086:Lentivirus; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D012497:Sandhoff Disease / Q000276:immunology / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency; D014161:Transduction, Genetic; D014611:Vaccination / Q000379:methods
C513080:Hhex protein, mouse; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D014157:Transcription Factors; D017493:Leukocyte Common Antigens