Expression of inducible nitric oxide synthase and elevation of tyrosine nitration of a 32-kilodalton cellular protein in brain capillary endothelial cells from rats infected with a neuropathogenic murine leukemia virus.
PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV (F-MuLV) which causes a rapidly progressive spongiform neurodegenerative disease in rodents. The primary target of PVC-211 MuLV infection in the brain is the brain capillary endothelial cell (BCEC), which is resistant to F-MuLV infection. Previous studies have shown that changes in the envelope gene of PVC-211 MuLV confer BCEC tropism to the virus. However, little is known about how infection of BCECs by PVC-211 MuLV induces neurological disease. Previous results suggest that nitric oxide (NO), which has been implicated as a potential neurotoxin, is involved in PVC-211 MuLV-induced neurodegeneration. In this study, we show that expression of inducible nitric oxide synthase (iNOS), which produces NO from L-arginine, is induced in BCECs from PVC-211 MuLV-infected rats. Furthermore, elevated levels of a 32-kDa cellular protein modified by 3-nitrotyrosine, which is a hallmark of NO production, were observed in virus-infected BCECs. BCECs from rats infected with BCEC-tropic but nonneuropathogenic PVF-e5 MuLV, which is a chimeric virus between PVC-211 MuLV and F-MuLV, fail to induce either iNOS expression or elevation of tyrosine nitration of a 32-kDa protein. These results suggest that expression of iNOS and nitration of tyrosine residues of a 32-kDa protein in PVC-211 MuLV-infected BCECs may play an important role in neurological disease induction.
Jinno-Oue
Atsushi
A
Basic Research Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA.
Wilt
Susan G
SG
Hanson
Charlotte
C
Dugger
Natalie V
NV
Hoffman
Paul M
PM
Masuda
Michiaki
M
Ruscetti
Sandra K
SK
D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D002196:Capillaries / Q000821:virology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000821:virology*; D009052:Leukemia Virus, Murine / Q000472:pathogenicity*; D051379:Mice; D009420:Nervous System / Q000473:pathology / Q000821:virology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012192:Retroviridae Infections / Q000503:physiopathology / Q000821:virology; D014412:Tumor Virus Infections / Q000503:physiopathology / Q000821:virology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D011506:Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat