TY - JOUR
T1 - Interferon-γ induced type I nitric oxide synthase activity inhibits viral replication in neurons
AU - Komatsu, Takashi
AU - Bi, Zhengbiao
AU - Reiss, Carol S.
N1 - Funding Information:
This work was supported by a grant from the NIH AI18083 and a Bridge grant from the Faculty of Arts and Science of NYU to CSR. Ted Dawson, Johns Hopkins University generously provided anti-NOS type I peptide antibody and provocative discussions. Other discussions of the work in progress which were stimulating were with David Bredt (University of California, San Francisco), Anthony Young (Ohio State), FY Liew (Glasgow), and Alice Huang (NYU). Viruses and cell lines were generously provided by V. Racaniello and B. Levine (College of Physicians and Surgeons), P. Schaffer (Dana-Farber Cancer Institute), and P. Palese (Mt Sinai School of Medicine). IL-12 was generously provided by Genetics Institute. We would like to thank Dr. Shirley Bartido for assistance with the immunoprecipitation, electrophoresis, and autoradiography, and Shelli Ann Oien for technical support.
PY - 1996/8
Y1 - 1996/8
N2 - Type I NOS expression increases in OB neurons during VSV infection. Immunocytochemical Staining of NB41A3 cells indicates constitutive expression of interferon (IFN)-γ receptor and type I NOS. IFN-γ treatment of NB41A3 cells increased NO production and type 1 NOS protein. In vitro replication of VSV, polio virus type 1, and Herpes Simplex virus type 1 (HSV-1) is significantly inhibited by IFN-γ induced type I NOS and antagonized by NOS inhibitors. In contrast, while IFN-γ treatment inhibited influenza and Sindbis virus replication, a different pathway(s) was involved. The isoform-selective NOS inhibitor, 7-nitroindazole (7NI) was used to treat mice, resulting in a 10-fold higher titer of virus in brain homogenates, and abrogated the recovery-promoting effect of interleukin-12 treatment. Thus, IFN-γ induced type I NOS activity may play an important role in host immunity against neurotropic viral infections.
AB - Type I NOS expression increases in OB neurons during VSV infection. Immunocytochemical Staining of NB41A3 cells indicates constitutive expression of interferon (IFN)-γ receptor and type I NOS. IFN-γ treatment of NB41A3 cells increased NO production and type 1 NOS protein. In vitro replication of VSV, polio virus type 1, and Herpes Simplex virus type 1 (HSV-1) is significantly inhibited by IFN-γ induced type I NOS and antagonized by NOS inhibitors. In contrast, while IFN-γ treatment inhibited influenza and Sindbis virus replication, a different pathway(s) was involved. The isoform-selective NOS inhibitor, 7-nitroindazole (7NI) was used to treat mice, resulting in a 10-fold higher titer of virus in brain homogenates, and abrogated the recovery-promoting effect of interleukin-12 treatment. Thus, IFN-γ induced type I NOS activity may play an important role in host immunity against neurotropic viral infections.
KW - Interferon-γ
KW - Neuronal nitric oxide synthase
KW - Viral infection
UR - http://www.scopus.com/inward/record.url?scp=0030217887&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030217887&partnerID=8YFLogxK
U2 - 10.1016/0165-5728(96)00083-5
DO - 10.1016/0165-5728(96)00083-5
M3 - Article
C2 - 8784266
AN - SCOPUS:0030217887
SN - 0165-5728
VL - 68
SP - 101
EP - 108
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -