The Journal of Immunology, Vol 148, Issue 3 881-887, Copyright © 1992 by American Association of Immunologists

ARTICLES

Virus-induced loss of class I MHC antigens from the surface of cells infected with myxoma virus and malignant rabbit fibroma virus

LK Boshkov, JL Macen and G McFadden
Department of Medicine, University of Alberta, Edmonton, Canada.

Shope fibroma virus (SFV) is a leporipoxvirus that causes localized benign fibromas in immunocompetent adult rabbits that spontaneously regress due, in part, to a cell-mediated immune response. Myxoma virus (MYX) and malignant rabbit fibroma virus (MRV) are related leporipoxviruses that induce rapidly lethal generalized infections accompanied by tumors and immunosuppression. Because only these latter two viruses are known to compromise cell-mediated antiviral responses, cell surface levels of class I MHC molecules in SFV-, MRV-, and MYX- infected cells were investigated by fluorescent activated cell sorting analysis using a variety of different anti-HLA mAb. After infection with MYX or MRV there is a rapid decrease in the levels of detectable surface class I epitopes as detected by each antibody and by 24 h postinfection class I MHC Ag levels at the cell surface approach the level of background fluorescence observed with control antibodies. In contrast, only a moderate class I decrease is seen during infection with either SFV or vaccinia virus, an orthopoxvirus that is neither tumorigenic nor immunosuppressive. Surface class I marker loss induced by MYX and MRV is not simply due to nonspecific inhibition of total cellular protein synthesis by the viruses because class I levels decrease much further than the extent measured by estimating surface marker turnover in the presence of the protein synthesis inhibitor cycloheximide. Thus the loss of cellular surface class I molecules greatly exceeds the drop in level caused by complete blockage of host cell gene expression, and must involve removal or masking of preexisting class I epitopes from the cell surface by MRV/MYX. Cell surface levels of the transferrin receptor are unaffected by MYX and MRV infection, suggesting the observed class I decrease is not a nonspecific effect on total cell surface glycoproteins. Analysis of cells infected with MRV/MYX in the presence of cycloheximide or of cytosine arabinoside, an inhibitor of poxviral DNA replication, indicates that the class I marker loss is mediated in part by one or more viral late gene products. A probable explanation is that MRV/MYX late protein(s) interact with the class I MHC complex to either physically sequester these away from the cell surface and inhibit their recycling or else induce a conformational change that precludes recognition by all class I antibodies tested. In either event, we propose that such a major perturbation of the class I MHC complex would likely downregulate the class I-mediated presentation of viral Ag required to initiate cell-mediated immunity to these viruses.

This article has been cited by other articles:

				S. E. Chisholm and H. T. Reyburn Recognition of Vaccinia Virus-Infected Cells by Human Natural Killer Cells Depends on Natural Cytotoxicity Receptors J. Virol., March 1, 2006; 80(5): 2225 - 2233. [Abstract] [Full Text] [PDF]

				J.-L. Guerin, J. Gelfi, S. Boullier, M. Delverdier, F.-A. Bellanger, S. Bertagnoli, I. Drexler, G. Sutter, and F. Messud-Petit Myxoma Virus Leukemia-Associated Protein Is Responsible for Major Histocompatibility Complex Class I and Fas-CD95 Down-Regulation and Defines Scrapins, a New Group of Surface Cellular Receptor Abductor Proteins J. Virol., February 22, 2002; 76(6): 2912 - 2923. [Abstract] [Full Text] [PDF]

				F. Messud-Petit, J. Gelfi, M. Delverdier, M.-F. Amardeilh, R. Py, G. Sutter, and S. Bertagnoli Serp2, an Inhibitor of the Interleukin-1beta -Converting Enzyme, Is Critical in the Pathobiology of Myxoma Virus J. Virol., October 1, 1998; 72(10): 7830 - 7839. [Abstract] [Full Text] [PDF]

				D. G. Baker Natural Pathogens of Laboratory Mice, Rats, and Rabbits and Their Effects on Research Clin. Microbiol. Rev., April 1, 1998; 11(2): 231 - 266. [Abstract] [Full Text] [PDF]