Prolonged survival of rat liver allograft with adenoviral gene transfection of human immunodeficiency virus type 1 nef.
HIV-1 nef is believed to allow immune evasion by modifying cell surface molecules because of certain mechanisms such as downregulation of the major histocompatibility complex (MHC) class I molecule complex as well as upregulation of FasL. In the present study, we successfully generated a recombinant adenovirus vector containing HIV-1 nef. We detected the expression of nef in liver infected with AxCANef by immune staining and Western blotting, and confirmed its expression as persistent for more than 4 weeks. Furthermore, the surface expression of MHC class I was downregulated in AxCANef-infected hepatic cells. In addition, we also observed nef-induced FasL upregulation of gene-transfected hepatic cells. Using a DA-to-Lewis orthotopic liver transplantation model, we transfected AxCANef to a liver graft to determine whether nef expression could have an effect on recipient survival. AxCANef significantly prolonged recipient survival time (14.5 days) compared with the uninfected group (11 days) (P <.001) and the AxCALacZ-infected group (11 days) (P <.001). Histologic analysis showed reduction in the number of accumulated inflammatory cells and an increase in apoptotic cells in grafts expressing nef. In conclusion, we showed that the nef gene could prolong survival of rat liver allografts, and this result suggested the potential clinical use of its transfection.
Fujino
Masayuki
M
Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.
Adachi
Kensuke
K
Kawasaki
Mikiko
M
Kitazawa
Yusuke
Y
Funeshima
Naoko
N
Okuyama
Torayuki
T
Kimura
Hiromitsu
H
Li
Xiao-Kang
XK
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003360:Cosmids; D015536:Down-Regulation / Q000502:physiology; D053222:Fas Ligand Protein; D015967:Gene Expression Regulation, Viral; D005805:Genes, MHC Class I; D015754:Genes, nef; D015497:HIV-1 / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism; D007150:Immunohistochemistry; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D014162:Transfection
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins