Transcripts expressed in cytomegalovirus latency coding for an antigenic IE/E phase peptide that drives 'memory inflation'
| Autor: | Niels A. W. Lemmermann, Birgit Kühnapfel, Angélique Renzaho, Julia K Schmiedeke, Christof K. Seckert, Marion Griessl |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Muromegalovirus 030106 microbiology Immunology Antigen presentation CD8-Positive T-Lymphocytes Major histocompatibility complex Virus Epitope Epitopes 03 medical and health sciences MHC class I Animals Immunology and Allergy Cytotoxic T cell Latency (engineering) Antigens Viral Gene biology Gene Expression Profiling General Medicine Virology Virus Latency Disease Models Animal 030104 developmental biology Cytomegalovirus Infections biology.protein Immunologic Memory |
| Zdroj: | Medical Microbiology and Immunology. 208:439-446 |
| ISSN: | 1432-1831 0300-8584 |
| DOI: | 10.1007/s00430-019-00615-8 |
| Popis: | 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 Ld. The only known second MI-driving antigenic peptide of mCMV in the murine MHC haplotype H-2d is AGPPRYSRI presented by the MHC-I molecule Dd. 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. |
| Databáze: | OpenAIRE |
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