The Immunoevasive Function Encoded by the Mouse Cytomegalovirus Gene m152 Protects the Virus Against T Cell Control In Vivo

doi:10.1084/jem.190.9.1285

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© The Rockefeller University Press, 0022-1007/1999/11/1285/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 9, November 1, 1999 1285-1296

Original Article

The Immunoevasive Function Encoded by the Mouse Cytomegalovirus Gene m152 Protects the Virus Against T Cell Control In Vivo

Astrid Krmpotic^a, Martin Messerle^b, Irena Crnkovic-Mertens^b, Bojan Polic^a, Stipan Jonjic^a, and Ulrich H. Koszinowski^b
^a Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
^b Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, D-80336 Munich, Germany

Correspondence to: Ulrich H. Koszinowski, Max von Pettenkofer-Institut, Pettenkoferstr. 9a, D-80336 München, Germany. Tel:49-89-5160-5290 Fax:49-89-5160-5292 E-mail:koszinowski{at}m3401.mpk.med.uni-muenchen.de.

Cytomegaloviruses encode numerous functions that inhibit antigenpresentation in the major histocompatibility complex (MHC) classI pathway in vitro. One example is the mouse cytomegalovirus(MCMV) glycoprotein gp40, encoded by the m152 gene, which selectivelyretains murine but not human MHC class I complexes in the endoplasmicreticulum–Golgi intermediate compartment/cis-Golgi compartment(Ziegler, H., R. Thäle, P. Lucin, W. Muranyi, T. Flohr,H. Hengel, H. Farrell, W. Rawlinson, and U.H. Koszinowski. 1997.Immunity. 6:57–66). To investigate the in vivo significanceof this gene function during MCMV infection of the natural host,we constructed recombinants of MCMV in which the m152 gene wasdeleted, as were the corresponding virus revertants. We reporton the following findings: Deletion of the m152 gene has noeffect on virus replication in cell culture, whereas after infectionof mice, the m152-deficient virus replicates to significantlylower virus titers. This attenuating effect is lifted by reinsertionof the gene into the mutant. Mutants and revertants grow tothe same titer in animals deprived of the function targetedby the viral gene function, namely in mice deficient in ß2-microglobulin,mice deficient in the CD8 molecule, and mice depleted of T cells.Upon adoptive transfer of naive lymphocytes into infected mice,the absence of the m152 gene function sensitizes the virus toprimary lymphocyte control. These results prove that MHC-reactivefunctions protect CMVs against attack by CD8⁺ T lymphocytesin vivo.

Key Words: cytomegalovirus, immune evasion, virus mutants, MHC class I,CD8, T lymphocytes

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