Human cytomegalovirus infection interferes with major histocompatibility complex type II maturation and endocytic proteases in dendritic cells at multiple levels
- PMID: 18796710
- DOI: 10.1099/vir.0.2008/001610-0
Human cytomegalovirus infection interferes with major histocompatibility complex type II maturation and endocytic proteases in dendritic cells at multiple levels
Abstract
Human cytomegalovirus (HCMV) infection suppresses cellular immunity and results in viral persistence. Dendritic cells (DCs) are susceptible to HCMV, and the development and immune function of HCMV-infected DCs are impaired in vitro. HCMV-derived proteins interfere with different aspects of major histocompatibility complex type II (MHC II) maturation and function in genetically engineered cellular models. This study directly analysed the effect of HCMV on the MHC II-associated antigen processing and presentation machinery in HCMV-infected human DCs in vitro. HCMV-infected DCs failed to mature newly synthesized MHC II to the final stage of SDS-stable MHC II alphabeta dimer/peptide complexes, in contrast to mock-infected controls. MHC II biosynthesis was delayed and reduced, whilst MHC II stability remained unchanged. MHC II surface expression was decreased in the late phase of HCMV infection. In addition, infected DCs decreased the transcription rate of the MHC II-associated proteases cathepsins S, Z, B, H and L and asparagine-specific endopeptidase (AEP). This translated into reduced protein expression of cathepsins H and S, as well as AEP, and less-efficient proteolytic degradation of a peptide substrate by endocytic proteases from HCMV-infected DCs in vitro. Thus, HCMV infection interferes with MHC II biosynthesis and maturation, as well as with the expression and function of endocytic proteases in infected DCs.
Similar articles
-
Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells.Blood. 2002 Apr 15;99(8):2913-21. doi: 10.1182/blood.v99.8.2913. Blood. 2002. PMID: 11929782
-
Human Cytomegalovirus Decreases Major Histocompatibility Complex Class II by Regulating Class II Transactivator Transcript Levels in a Myeloid Cell Line.J Virol. 2020 Mar 17;94(7):e01901-19. doi: 10.1128/JVI.01901-19. Print 2020 Mar 17. J Virol. 2020. PMID: 31915281 Free PMC article.
-
Dendritic cell function in cytomegalovirus-infected patients with mononucleosis.J Leukoc Biol. 2006 May;79(5):932-40. doi: 10.1189/jlb.0905499. Epub 2006 Feb 24. J Leukoc Biol. 2006. PMID: 16501053
-
Inhibition of the MHC class II antigen presentation pathway by human cytomegalovirus.Curr Top Microbiol Immunol. 2002;269:101-15. doi: 10.1007/978-3-642-59421-2_7. Curr Top Microbiol Immunol. 2002. PMID: 12224504 Review.
-
Human cytomegalovirus infection of immature dendritic cells and macrophages.Intervirology. 1999;42(5-6):365-72. doi: 10.1159/000053973. Intervirology. 1999. PMID: 10702719 Review.
Cited by
-
Role of cytomegalovirus on the maturation and function of monocyte derived dendritic cells of liver transplant patients.World J Transplant. 2016 Jun 24;6(2):336-46. doi: 10.5500/wjt.v6.i2.336. World J Transplant. 2016. PMID: 27358779 Free PMC article.
-
Cytomegalovirus expresses the chemokine homologue vXCL1 capable of attracting XCR1+ CD4- dendritic cells.J Virol. 2014 Jan;88(1):292-302. doi: 10.1128/JVI.02330-13. Epub 2013 Oct 23. J Virol. 2014. PMID: 24155383 Free PMC article.
-
Human Macrophages Escape Inhibition of Major Histocompatibility Complex-Dependent Antigen Presentation by Cytomegalovirus and Drive Proliferation and Activation of Memory CD4+ and CD8+ T Cells.Front Immunol. 2018 May 25;9:1129. doi: 10.3389/fimmu.2018.01129. eCollection 2018. Front Immunol. 2018. PMID: 29887865 Free PMC article.
-
Human cytomegalovirus decreases constitutive transcription of MHC class II genes in mature Langerhans cells by reducing CIITA transcript levels.Mol Immunol. 2011 May;48(9-10):1160-7. doi: 10.1016/j.molimm.2011.02.010. Epub 2011 Mar 31. Mol Immunol. 2011. PMID: 21458073 Free PMC article.
-
Dendritic cells are susceptible to infection with wild-type adenovirus, inducing a differentiation arrest in precursor cells and inducing a strong T-cell stimulation.J Gen Virol. 2010 May;91(Pt 5):1150-4. doi: 10.1099/vir.0.013920-0. Epub 2009 Dec 23. J Gen Virol. 2010. PMID: 20032205 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials