Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment

Selective expression of murine cytomegalovirus (MCMV)
immediate-early (IE) genes leads to the presentation by the major
histocompatibility complex (MHC) class I molecule L a of a peptide
derived from MCMV IE protein pp89 (Reddehase, M. J., J. B.
Rothbard, and U. H. Koszinowski. 1989. Nature (Lond.). 337:651).
Characterization of endogenous antigenic peptides identified the
pp89 peptide as the nonapeptide msYPHFMFFNLt76 (del Val, M., H.-J.
Schlicht, T. Ruppert, M. J. Reddehase, and U. H. Koszinowski. 1991.
Cell. 66:1145). Subsequent expression of MCMV early genes prevents
presentation of pp89 (del Val, M., K. Mfinch, M. J. Reddehase, and
U. H. Koszinowski. 1989. Cell. 58:305). We report on the mechanism
by which MCMV early genes interfere with antigen presentation.
Expression of the IE promoter-driven bacterial gene lacZ by
recombinant MCMV subjected antigen presentation of B-galactosidase
to the same control and excluded antigen specificity. The
La-dependent presence of naturally processed antigenic peptides
also in nonpresenting cells located the inhibitory function
subsequent to the step of antigen processing. The finding that
during the E phase of MCMV gene expression the MHC class I heavy
chain glycosylation remained in an Endo H-sensitive form suggested
a block within the endoplasmic reticulum/c/s-Golgi compartment. The
failure to present antigenic peptides was explained by a general
retention of nascent assembled trimolecular MHC class I complexes.
Accordingly, at later stages of infection a significant decrease of
surface MHC class I expression was seen, whereas other membrane
glycoproteins remained unaffected. Thus, MCMV E genes endow this
virus with an effective immune evasion potential. These results
also indicate that the formation of the trimolecular complex of MHC
dass I heavy chain, ~2-microglobulin, and the finally trimmed
peptide is completed before entering the medial-Golgi compartment.