Capillary endothelial cell tropism of PVC-211 murine leukemia virus and its application for gene transduction.
PVC-211 murine leukemia virus (MuLV) causes neurodegenerative disease following inoculation of neonatal, but not adult, mice and rats. It was previously shown that tropism for brain capillary endothelial cells (CEC) was a determinant of the viral neuropathogenicity. In this study, we demonstrate that host age-dependent replication of PVC-211 MuLV in vivo occurs in CEC in the brain as well as in other organs, such as the liver, kidney, and heart. In contrast, primary explant cultures of CEC derived from brains and livers of adult and neonatal rats could be infected by PVC-211 MuLV, suggesting that the age-dependent susceptibility was abrogated in vitro. Although CEC were generally less susceptible to MuLV-mediated gene transduction than fibroblasts, treatment of CEC with 2-deoxyglucose followed by inoculation of a PVC-211 MuLV-pseudotyped vector in the absence of heparin improved the transduction efficiency. These observations support the possibility that PVC-211 MuLV may be useful for establishing models of CEC gene transduction.
Masuda
M
M
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702, USA.
Hanson
C A
CA
Dugger
N V
NV
Robbins
D S
DS
Wilt
S G
SG
Ruscetti
S K
SK
Hoffman
P M
PM
D000818:Animals; D001921:Brain / Q000821:virology; D002196:Capillaries / Q000821:virology; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000821:virology*; D005622:Friend murine leukemia virus / Q000502:physiology*; D018014:Gene Transfer Techniques; D008099:Liver / Q000821:virology; D051381:Rats; D011916:Rats, Inbred F344
D003847:Deoxyglucose