Abstract
ABSTRACT We and others have shown that infection of dendritic cells with murine cytomegalovirus (MCMV) leads to severe functional impairment of these antigen-presenting cells (D. M. Andrews, C. E. Andoniou, F. Granucci, P. Ricciardi-Castagnoli, and M. A. Degli-Esposti, Nat. Immunol. 2: 1077-1084, 2001; S. Mathys, T. Schroeder, J. Ellwart, U. H. Koszinowski, M. Messerle, and U. Just, J. Infect. Dis. 187: 988-999, 2003). Phenotypically, reduced surface expression of costimulatory molecules and major histocompatibility complex molecules was detected. In order to identify the molecular basis for the observed effects, we generated MCMV mutants with large deletions of nonessential genes. The study was facilitated by the finding that a monocyte-macrophage cell line displayed similar phenotypic alterations after MCMV infection. By analyzing the expression of cell surface molecules on infected cells, we identified a mutant virus which is no longer able to downmodulate the expression of the costimulatory molecule CD86. Additional mutants with smaller deletions allowed us to pin down the responsible gene to a certain genomic region. RNA analysis led to the identification of the spliced gene m147.5, encoding a protein with 145 amino acids. Experiments with an m147.5 mutant revealed that the protein affects CD86 expression only, suggesting that additional MCMV genes are responsible for downmodulation of the other surface molecules. Identification of viral gene products interfering with functionally important proteins of antigen-presenting cells will provide the basis to dissect the complex interaction of CMV with these important cells and to evaluate the biological importance of these viral genes in vivo.
References
64
Referenced
51
10.1002/rmv.380
10.1128/JVI.74.15.6964-6974.2000
10.1016/S0966-842X(00)01830-8
10.1038/ni724
10.1128/JVI.76.17.8596-8608.2002
10.1146/annurev.immunol.18.1.767
10.1038/32588
10.1002/eji.200323612
10.1128/JVI.73.10.8320-8329.1999
- Borst, E. M., G. Posfai, F. Pogoda, and M. Messerle. 2004. Mutagenesis of herpesvirus BACs by allele replacement, p. 269-280. In S. Zhao and M. Stodolsky (ed.), Bacterial artificial chromosomes, vol. 2: functional studies. Humana Press Inc., Totowa, N.J. / Bacterial artificial chromosomes, vol. 2: functional studies (2004)
- Brune W. H. Hengel and U. H. Koszinowski. 1999. Current protocols in immunology p. 19.7.1-19.7.13. John Wiley & Sons New York N.Y.
10.1126/science.291.5502.303
10.1038/7914
10.1016/S0168-9525(00)02015-1
10.1128/JVI.77.21.11633-11643.2003
10.1016/0378-1119(95)00193-A
10.1084/jem.20021522
10.1073/pnas.120163297
10.1099/vir.0.18606-0
10.1073/pnas.2334032100
10.1111/j.1600-065X.1999.tb01293.x
10.1128/JVI.77.20.10943-10956.2003
10.1046/j.1365-2141.2002.03798.x
- Gutermann, A., A. Bubeck, M. Wagner, U. Reusch, C. Menard, and U. H. Koszinowski. 2002. Strategies for the identification and analysis of viral immune-evasive genes—cytomegalovirus as an example. Curr. Top. Microbiol. Immunol.269:1-22. / Curr. Top. Microbiol. Immunol. (2002)
10.1128/JVI.76.18.9551-9555.2002
10.1128/JVI.73.7.5970-5980.1999
10.1084/jem.187.7.1037
10.1016/S0966-842X(98)01255-4
10.1128/JVI.77.13.7563-7574.2003
10.1093/bioinformatics/14.4.378
10.1128/JVI.74.17.7720-7729.2000
10.1159/000053973
10.1016/S1369-5274(02)00334-X
10.1006/smim.2001.0292
10.1016/0092-8674(78)90046-6
10.1006/smim.2001.0294
10.1016/S0022-1759(98)00204-X
10.1086/368094
10.1128/JVI.77.10.5557-5570.2003
10.1128/jvi.66.1.27-36.1992
10.1073/pnas.94.26.14759
- Mocarski, E. S., and C. T. Courcelle. 2001. Cytomegaloviruses and their replication, p. 2629-2674. In D. M. Knipe and P. M. Howley (ed.), Fields virology. Lippincott Williams & Wilkins-Raven Publishers, New York, N.Y. / Fields virology (2001)
10.1093/nar/10.2.459
10.1128/JVI.78.6.3046-3054.2004
10.1182/blood.V99.8.2913
10.1073/pnas.1735466100
- Pass, R. F. 2001. Cytomegalovirus, p. 2675-2705. In D. M. Knipe and P. M. Howley (ed.), Fields virology. Lippincott Williams & Wilkins, Philadelphia, Pa. / Fields virology (2001)
10.1073/pnas.1835673100
10.1016/S1074-7613(01)00239-4
10.1016/0092-8674(78)90101-0
10.1128/jvi.70.12.8833-8849.1996
10.1038/nri932
- Riegler, S., H. Hebart, H. Einsele, P. Brossart, G. Jahn, and C. Sinzger. 2000. Monocyte-derived dendritic cells are permissive to the complete replicative cycle of human cytomegalovirus. J. Gen. Virol.81:393-399. / J. Gen. Virol. (2000)
- Sambrook J. F. and D. W. Russell. 2000. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press Cold Spring Harbor N.Y.
10.1182/blood-2003-12-4350
10.1128/jvi.68.10.6243-6253.1994
10.1126/science.288.5465.522
10.1084/jem.20020811
10.1128/JVI.73.8.7056-7060.1999
10.1016/S0966-842X(02)02394-6
10.1073/pnas.1635160100
10.1128/jvi.76.5.2316-2328.2002
10.1093/nar/gkg241
10.1038/2417
Dates
Type | When |
---|---|
Created | 20 years, 9 months ago (Nov. 12, 2004, 3:29 p.m.) |
Deposited | 3 years, 5 months ago (March 5, 2022, 3:55 a.m.) |
Indexed | 5 months ago (March 31, 2025, 6:25 p.m.) |
Issued | 20 years, 9 months ago (Dec. 1, 2004) |
Published | 20 years, 9 months ago (Dec. 1, 2004) |
Published Print | 20 years, 9 months ago (Dec. 1, 2004) |
@article{Loewendorf_2004, title={Identification of a Mouse Cytomegalovirus Gene Selectively Targeting CD86 Expression on Antigen-Presenting Cells}, volume={78}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.78.23.13062-13071.2004}, DOI={10.1128/jvi.78.23.13062-13071.2004}, number={23}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Loewendorf, Andrea and Krüger, Corinna and Borst, Eva Maria and Wagner, Markus and Just, Ursula and Messerle, Martin}, year={2004}, month=dec, pages={13062–13071} }