PMID- 31004200
OWN - NLM
STAT- MEDLINE
DCOM- 20191206
LR  - 20200424
IS  - 1432-1831 (Electronic)
IS  - 0300-8584 (Linking)
VI  - 208
IP  - 3-4
DP  - 2019 Aug
TI  - Transcripts expressed in cytomegalovirus latency coding for an antigenic IE/E 
      phase peptide that drives "memory inflation".
PG  - 439-446
LID - 10.1007/s00430-019-00615-8 [doi]
AB  - Roizman's definition of herpesviral latency, which applies also to 
      cytomegaloviruses (CMVs), demands maintenance of reactivation-competent viral 
      genomes after clearance of productive infection. It is more recent understanding 
      that failure to complete the productive viral cycle for virus assembly and 
      release does not imply viral gene silencing at all genetic loci and all the time. 
      It rather appears that CMV latency is transcriptionally "noisy" in that silenced 
      viral genes get desilenced from time to time in a stochastic manner, leading to 
      "transcripts expressed in latency" (TELs). If a TEL happens to code for a protein 
      that contains a CD8 T cell epitope, protein processing can lead to the 
      presentation of the antigenic peptide and restimulation of cognate CD8 T cells 
      during latency. This mechanism is discussed as a potential driver of 
      epitope-selective accumulation of CD8 T cells over time, a phenomenon linked to 
      CMV latency and known as "memory inflation" (MI). So far, expression of an 
      epitope-encoding TEL was shown only for the major immediate-early (MIE) gene 
      m123/ie1 of murine cytomegalovirus (mCMV), which codes for the prototypic 
      MI-driving antigenic peptide YPHFMPTNL that is presented by the MHC class-I 
      molecule L(d). The only known second MI-driving antigenic peptide of mCMV in the 
      murine MHC haplotype H-2(d) is AGPPRYSRI presented by the MHC-I molecule D(d). 
      This peptide is very special in that it is encoded by the early (E) phase gene 
      m164 and by an overlapping immediate-early (IE) transcript governed by a promoter 
      upstream of m164. If MI is driven by presentation of TEL-derived antigenic 
      peptides, as the hypothesis says, one should find corresponding TELs. We show 
      here that E-phase and IE-phase transcripts that code for the MI-driving antigenic 
      peptide AGPPRYSRI are independently and stochastically expressed in latently 
      infected lungs.
FAU - Renzaho, Angelique
AU  - Renzaho A
AD  - Institute for Virology, University Medical Center, Johannes Gutenberg-University 
      Mainz and Research Center for Immunotherapy (FZI), Obere Zahlbacher Strasse 67, 
      Hochhaus am Augustusplatz, 55131, Mainz, Germany.
FAU - Schmiedeke, Julia K
AU  - Schmiedeke JK
AD  - Institute for Virology, University Medical Center, Johannes Gutenberg-University 
      Mainz and Research Center for Immunotherapy (FZI), Obere Zahlbacher Strasse 67, 
      Hochhaus am Augustusplatz, 55131, Mainz, Germany.
FAU - Griessl, Marion
AU  - Griessl M
AD  - Institute for Virology, University Medical Center, Johannes Gutenberg-University 
      Mainz and Research Center for Immunotherapy (FZI), Obere Zahlbacher Strasse 67, 
      Hochhaus am Augustusplatz, 55131, Mainz, Germany.
AD  - Morgan Sindall Professional Services AG, Basel, Switzerland.
FAU - Kuhnapfel, Birgit
AU  - Kuhnapfel B
AD  - Institute for Virology, University Medical Center, Johannes Gutenberg-University 
      Mainz and Research Center for Immunotherapy (FZI), Obere Zahlbacher Strasse 67, 
      Hochhaus am Augustusplatz, 55131, Mainz, Germany.
FAU - Seckert, Christof K
AU  - Seckert CK
AD  - Institute for Virology, University Medical Center, Johannes Gutenberg-University 
      Mainz and Research Center for Immunotherapy (FZI), Obere Zahlbacher Strasse 67, 
      Hochhaus am Augustusplatz, 55131, Mainz, Germany.
AD  - Institute for Medical Microbiology and Hygiene, University Medical Center, 
      Johannes Gutenberg-University Mainz, Obere Zahlbacher Strasse 67, Hochhaus am 
      Augustusplatz, 55131, Mainz, Germany.
FAU - Lemmermann, Niels A W
AU  - Lemmermann NAW
AUID- ORCID: 0000-0001-9190-6497
AD  - Institute for Virology, University Medical Center, Johannes Gutenberg-University 
      Mainz and Research Center for Immunotherapy (FZI), Obere Zahlbacher Strasse 67, 
      Hochhaus am Augustusplatz, 55131, Mainz, Germany. lemmermann@uni-mainz.de.
LA  - eng
GR  - SFB1292 TP11/Deutsche Forschungsgemeinschaft/
GR  - SFB1292 TP11/Deutsche Forschungsgemeinschaft/
GR  - SFB490 E4/Deutsche Forschungsgemeinschaft/
GR  - SFB490 E4/Deutsche Forschungsgemeinschaft/
GR  - SFB490 E4/Deutsche Forschungsgemeinschaft/
GR  - SFB1292 TP11/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
DEP - 20190419
PL  - Germany
TA  - Med Microbiol Immunol
JT  - Medical microbiology and immunology
JID - 0314524
RN  - 0 (Antigens, Viral)
RN  - 0 (Epitopes)
SB  - IM
MH  - Animals
MH  - Antigens, Viral/biosynthesis/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cytomegalovirus Infections/*immunology/*virology
MH  - Disease Models, Animal
MH  - Epitopes/biosynthesis/immunology
MH  - *Gene Expression Profiling
MH  - Immunologic Memory
MH  - Muromegalovirus/growth & development/*immunology
MH  - *Virus Latency
OTO - NOTNLM
OT  - Antigen presentation
OT  - Antigenic peptide(s)
OT  - CD8 T cells
OT  - Gene m164
OT  - IE1 peptide
OT  - Latency
OT  - Latent infection
OT  - Memory inflation (MI)
OT  - RT-qPCR
OT  - Stochastic gene expression
OT  - Transcripts expressed in latency (TEL)
OT  - Viral gene expression
EDAT- 2019/04/21 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/04/21 06:00
PHST- 2019/04/03 00:00 [received]
PHST- 2019/04/11 00:00 [accepted]
PHST- 2019/04/21 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/04/21 06:00 [entrez]
AID - 10.1007/s00430-019-00615-8 [pii]
AID - 10.1007/s00430-019-00615-8 [doi]
PST - ppublish
SO  - Med Microbiol Immunol. 2019 Aug;208(3-4):439-446. doi: 
      10.1007/s00430-019-00615-8. Epub 2019 Apr 19.