Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4(+) T cells

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes life-t hreatening disease in patients who are immunosuppressed for bone marrow or tissue transplantation or who have AIDS (ref. 1). HCMV establishes lifelong latent infections and, after periodic: reactivation from latency, uses a p anel of immune evasion proteins to survive and replicate in the face of rob ust, fully primed host immunity(2,3). Monocyte/macrophages are important ho st cells for HCMV, serving as a latent reservoir and as a means of dissemin ation throughout the body(4). Macrophages and other HCMV-permissive cells, such as endothelial and glial cells, can express MHC class II proteins and present antigens to CD4+ T lymphocytes. Here, we show that the HCMV protein US2 causes degradation of two essential proteins in the MHC class II antig en presentation pathway: HLA-DR-c( and DM-a. This was unexpected, as US2 ha s been shown to cause degradation of MHC class I (refs. 5,6), which has onl y limited homology with class II proteins. Expression of US2 in cells reduc ed or abolished their ability to present antigen to CD4+ T lymphocytes. Thu s, US2 may allow HCMV-infected macrophages to remain relatively 'invisible' to CD4+ T cells, a property that would be important after virus reactivati on.