Abstract
ABSTRACTComplement regulatory protein CD46 is a human cell receptor for measles virus (MV). In this study, we investigated why mouse macrophages expressing human CD46 restricted MV replication and produced higher levels of nitric oxide (NO) in response to MV and gamma interferon (IFN-γ). Treatment of MV-infected CD46-expressing mouse macrophages with antibodies against IFN-α/β blocked NO production. Antibodies against IFN-α/β also inhibited the augmenting effect of MV on IFN-γ-induced NO production in CD46-expressing mouse macrophages. These antibodies did not affect NO production induced by IFN-γ alone. These data suggest that MV enhances NO production in CD46-expressing mouse macrophages through action of IFN-α/β. Mouse macrophages expressing a human CD46 mutant lacking the cytoplasmic domains were highly susceptible to MV. These cells produced much lower levels of NO and IFN-α/β upon infection by MV, suggesting the CD46 cytoplasmic domains enhanced IFN-α/β production. When mouse macrophages expressing tailless human CD46 were exposed to culture medium from MV-infected mouse macrophages expressing intact human CD46, viral protein synthesis and development of cytopathic effects were suppressed. Pretreating the added culture medium with antibodies against IFN-α/β abrogated these antiviral effects. Taken together, these findings suggest that expression of human CD46 in mouse macrophages enhances production of IFN-α/β in response to MV infection, and IFN-α/β synergizes with IFN-γ to enhance NO production and restrict viral protein synthesis and virus replication. This novel function of human CD46 in mouse macrophages requires the CD46 cytoplasmic domains.
References
42
Referenced
42
10.1006/viro.1994.1617
10.1006/viro.1998.9432
10.1016/0076-6879(81)78145-X
10.1128/jvi.63.3.1162-1173.1989
10.1093/infdis/170.Supplement_1.S15
- Borrow P. Oldstone M. B. A. Measles virus-mononuclear cell interactions.Curr. Top. Microbiol. Immunol. 191 1995 85 100 / Curr. Top. Microbiol. Immunol. / Measles virus-mononuclear cell interactions by Borrow P. (1995)
10.1089/aid.1992.8.575
10.1016/0165-2478(94)00246-N
10.1016/0092-8674(93)80071-L
10.1093/infdis/168.1.47
10.1089/jir.1993.13.271
10.1126/science.272.5258.50
-
Francis M. L. Meltzer M. S. Induction of IFN-α by HIV-1 in monocyte-enriched PBMC requires gp120-CD4 interaction but not virus replication.J. Immunol. 151 1993 2208 2216
(
10.4049/jimmunol.151.4.2208
) / J. Immunol. / Induction of IFN-α by HIV-1 in monocyte-enriched PBMC requires gp120-CD4 interaction but not virus replication by Francis M. L. (1993) 10.1016/S0021-9258(18)99942-4
10.1093/infdis/170.Supplement_1.S24
10.1006/viro.1998.9460
10.1128/JVI.73.6.4776-4785.1999
10.1128/jvi.70.10.6673-6681.1996
10.1006/viro.1996.0259
10.1006/bbrc.1998.9173
10.1006/viro.1995.1465
10.1111/j.1699-0463.1992.tb00850.x
-
Leopez-Collazo E. Horelano S. Rojas A. Bosca L. Triggering of peritoneal macrophages with IFN-α/β attenuates the expression of inducible nitric oxide synthase through a decrease in NF-κB activation.J. Immunol. 160 1998 2889 2895
(
10.4049/jimmunol.160.6.2889
) / J. Immunol. / Triggering of peritoneal macrophages with IFN-α/β attenuates the expression of inducible nitric oxide synthase through a decrease in NF-κB activation by Leopez-Collazo E. (1998) 10.1073/pnas.86.16.6348
10.1073/pnas.90.20.9730
10.1146/annurev.immunol.15.1.323
10.1016/S0952-7915(97)80152-5
10.1128/JVI.72.9.7420-7427.1998
10.1016/S0140-6736(96)07493-4
10.1128/jvi.67.10.6025-6032.1993
10.1016/S0092-8674(00)80050-1
10.1128/JVI.72.6.4547-4551.1998
10.1006/viro.1993.1363
10.1042/bj3300163
10.1128/jvi.65.12.6743-6748.1991
- Vilcek J. Sen G. C. Interferons and other cytokines Fundamental virology 3rd ed. Fields B. N. 1996 341 365 Lippincott-Raven Press New York N.Y
10.1139/m95-082
- Wong T. C. and A. Hirano. Roles of CD46 in measles virus infection: friend or foe? Res. Trends in press.
10.1084/jem.177.6.1779
10.1016/0165-5728(94)90193-7
10.1128/iai.62.1.33-40.1994
10.1089/jir.1995.15.897
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 27, 2002, 5:58 a.m.) |
Deposited | 2 years, 4 months ago (April 23, 2023, 11:04 a.m.) |
Indexed | 2 months, 3 weeks ago (June 11, 2025, 5:03 p.m.) |
Issued | 25 years, 7 months ago (Feb. 1, 2000) |
Published | 25 years, 7 months ago (Feb. 1, 2000) |
Published Print | 25 years, 7 months ago (Feb. 1, 2000) |
@article{Katayama_2000, title={Human Receptor for Measles Virus (CD46) Enhances Nitric Oxide Production and Restricts Virus Replication in Mouse Macrophages by Modulating Production of Alpha/Beta Interferon}, volume={74}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.74.3.1252-1257.2000}, DOI={10.1128/jvi.74.3.1252-1257.2000}, number={3}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Katayama, Yuko and Hirano, Akiko and Wong, Timothy C.}, year={2000}, month=feb, pages={1252–1257} }