Transcripts expressed in cytomegalovirus latency coding for an antigenic IE/E phase peptide that drives “memory inflation”

AbstractRoizman ’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 rele ase 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 h appens 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 t ime, 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) genem123/ie1 of murine cytomegalovirus (mCMV), which codes for the prototypic MI-driving antigenic peptideYPHFMPTNL 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 isAGPPRYSRI presented by the MHC-I molecule Dd. This peptide is very special in that it is encoded by the early (E) phase genem164 and by an ove...
Source: Medical Microbiology and Immunology - Category: Microbiology Source Type: research