Human cytomegalovirus protein pp65 mediates accumulation of HLA-DR in lysosomes and destruction of the HLA-DR α-chain
- 15 June 2003
- journal article
- Published by American Society of Hematology in Blood
- Vol. 101 (12) , 4870-4877
- https://doi.org/10.1182/blood-2002-05-1504
Abstract
Human cytomegalovirus (HCMV) has developed multiple strategies to escape immune recognition. Here, we demonstrate that HCMV down-regulates HLA-DR expression in infected interferon γ (IFN-γ)–stimulated fibroblasts at 1 day after infection. Decreased HLA-DR expression was not observed on cells infected with an HCMV strain lacking the pp65 gene (RVAD65), but was observed on cells transfected with the pp65 gene. HLA-DR expression accumulated in vacuoles near the nucleus in HCMV-infected, but not in uninfected or RVAD65-infected cells. In addition, the HLA-DR α-chain, but not the β-chain or HLA-DM, was degraded in HCMV-infected but not in RVAD65-infected cells. Thus, the HCMV protein pp65 mediates decreased expression of HLA-DR, by mediating an accumulation of HLA class II molecules in lysosomes that results in degradation of the HLA-DR α-chain.Keywords
This publication has 49 references indexed in Scilit:
- Human Cytomegalovirus Gene Products US2 and US11 Differ in Their Ability To Attack Major Histocompatibility Class I Heavy Chains in Dendritic CellsJournal of Virology, 2002
- Reduced Expression of HLA Class II Molecules and Interleukin-10- and Transforming Growth Factor β1-Independent Suppression of T-Cell Proliferation in Human Cytomegalovirus-Infected Macrophage CulturesJournal of Virology, 2001
- Dense Bodies of Human Cytomegalovirus Induce both Humoral and Cellular Immune Responses in the Absence of Viral Gene ExpressionJournal of Virology, 2000
- Human cytomegalovirus pp65 lower matrix phosphoprotein harbours two transplantable nuclear localization signalsJournal of General Virology, 1996
- The Human Cytomegalovirus US11 Gene Product Dislocates MHC Class I Heavy Chains from the Endoplasmic Reticulum to the CytosolCell, 1996
- Proliferative T Cell Responses to Four Human Cytomegalovirus-Specific Proteins in Healthy Subjects and Solid Organ Transplant RecipientsThe Journal of Infectious Diseases, 1995
- Regulation of MHC Class II Expression by Interferon-γ Mediated by the Transactivator Gene CIITAScience, 1994
- Identification of the major late human cytomegalovirus matrix protein pp65 as a target antigen for CD8+ virus‐specific cytotoxic T lymphocytesJournal of Medical Virology, 1994
- Cytomegalovirus Replication in Murine Microglial Cell Cultures: Suppression of Permissive Infection by Interferon-γThe Journal of Infectious Diseases, 1994
- Human Cytomegalovirus-associated DNA Polymerase and Protein Kinase ActivitiesJournal of General Virology, 1981