PMID- 18796710
OWN - NLM
STAT- MEDLINE
DCOM- 20081027
LR  - 20200302
IS  - 0022-1317 (Print)
IS  - 0022-1317 (Linking)
VI  - 89
IP  - Pt 10
DP  - 2008 Oct
TI  - Human cytomegalovirus infection interferes with major histocompatibility complex 
      type II maturation and endocytic proteases in dendritic cells at multiple levels.
PG  - 2427-2436
LID - 10.1099/vir.0.2008/001610-0 [doi]
AB  - 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.
FAU - Kessler, Tobias
AU  - Kessler T
AD  - Department of Virology, University of Tubingen, Tubingen, Germany.
FAU - Reich, Michael
AU  - Reich M
AD  - Department of Medicine II, University of Tubingen, Tubingen, Germany.
FAU - Jahn, Gerhard
AU  - Jahn G
AD  - Department of Virology, University of Tubingen, Tubingen, Germany.
FAU - Tolosa, Eva
AU  - Tolosa E
AD  - Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, 
      Germany.
FAU - Beck, Alexander
AU  - Beck A
AD  - Department of Medicine IV, University of Tubingen, Tubingen, Germany.
FAU - Kalbacher, Hubert
AU  - Kalbacher H
AD  - Natural Sciences Research Centre, University of Tubingen, Tubingen, Germany.
FAU - Overkleeft, Herman
AU  - Overkleeft H
AD  - Leiden Institute of Chemistry, University of Leiden, Leiden, The Netherlands.
FAU - Schempp, Susanne
AU  - Schempp S
AD  - Department of Virology, University of Tubingen, Tubingen, Germany.
FAU - Driessen, Christoph
AU  - Driessen C
AD  - Department of Medicine II, University of Tubingen, Tubingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Histocompatibility Antigens Class II)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Antigen Presentation
MH  - Cell Differentiation/*drug effects
MH  - Cells, Cultured
MH  - Cytomegalovirus/*pathogenicity
MH  - Cytomegalovirus Infections/*virology
MH  - Dendritic Cells/*cytology/metabolism/*virology
MH  - Endocytosis
MH  - Fibroblasts
MH  - Histocompatibility Antigens Class II/*metabolism
MH  - Humans
MH  - Monocytes/cytology
MH  - Peptide Hydrolases/*metabolism
EDAT- 2008/09/18 09:00
MHDA- 2008/10/28 09:00
CRDT- 2008/09/18 09:00
PHST- 2008/09/18 09:00 [pubmed]
PHST- 2008/10/28 09:00 [medline]
PHST- 2008/09/18 09:00 [entrez]
AID - 10.1099/vir.0.2008/001610-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2008 Oct;89(Pt 10):2427-2436. doi: 10.1099/vir.0.2008/001610-0.