title: Human cytomegalovirus pp71 stimulates major histocompatibility complex class i presentation of IE1-derived peptides at immediate early times of infection.
abstract: Suppression of major histocompatibility complex (MHC) class I-mediated presentation of human cytomegalovirus (HCMV) peptides is an important mechanism to avoid CD8 T lymphocyte recognition and killing of infected cells. Of particular interest is how MHC class I presentation of essential regulatory immediate early (IE) proteins of HCMV can be effectively compromised at times when known viral immunoevasins are not abundantly expressed. The tegument protein pp71 had been suggested to be involved in MHC class I downregulation. Intriguingly, this polypeptide is also critically engaged in the initial derepression of the major IE gene locus, leading to enhanced expression of IE proteins IE1-pp72 and IE2-pp86. Using a set of viral mutants, we addressed the role of pp71 in MHC class I presentation of IE1-pp72-derived peptides. We show that the amount of "incoming" pp71 positively correlates with IE1-pp72 protein levels and with the presentation of IE1-derived peptides. This indicates that the amount of the IE1 protein, induced by pp71, rather than a putative immunoevasive function of the tegument protein, determines MHC class I antigen presentation of IE1-derived peptides. This process proved to be independent of the presence of pp65, which had been reported to interfere with IE1 presentation. It may thus be beneficial for the success of HCMV replication to limit the level of pp71 delivered from infecting particles in order to avoid critical levels of MHC class I presentation of IE protein-derived peptides.
authors: Institute for Virology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors: Julia
authors: J
authors: Hesse
authors: Sabine
authors: S
authors: Reyda
authors: Stefan
authors: S
authors: Tenzer
authors: Katrin
authors: K
authors: Besold
authors: Nina
authors: N
authors: Reuter
authors: Steffi
authors: S
authors: Krauter
authors: Nicole
authors: N
authors: Büscher
authors: Thomas
authors: T
authors: Stamminger
authors: Bodo
authors: B
authors: Plachter
mesh_terms: D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010455:Peptides; D014764:Viral Proteins; C051298:cytomegalovirus phosphoprotein 71kDa