CMV and the Art of Memory Maintenance

Klenerman, Paul; Dunbar, P. Rod

doi:10.1016/j.immuni.2008.09.008

Cited by 17 publications

(13 citation statements)

References 11 publications

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“…Along with the IE1 epitope and with more recently identified epitopes from ORFs M105 and m145 [13], the m164 epitope proved to be immunodominant with respect to the frequency of CD8 T cells responding to it during the immune response to acute infection. In addition to the IE1 epitope, which is the prototype of an epitope that induces expansion of the memory CD8 T-cell pool at extralymphoid sites of latent mCMV infection [14], a phenomenon known today as “memory inflation” ([15], reviewed in [16,17,18]), the m164 epitope turned out to be the second inducer of memory inflation in the H-2 d haplotype, a property that it shares with three epitopes in the H-2 b haplotype [19] and that is thought to indicate episodes of limited viral gene expression during latency (for recent reviews, see [20,21]). As the ORF m164 protein, a non-essential ER-resident type-I glycoprotein of 36.5 kDa, is expressed as an Early (E) phase protein [22], it was assumed that the m164 peptide is presented not until the E phase.…”

Section: Introductionmentioning

confidence: 99%

Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene

Fink

Büttner

Thomas

et al. 2014

Viruses

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Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I) glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs) based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic class of the protein also defines the phase in the viral replicative cycle during which the respective antigenic peptide is presented for recognition by CD8 T cells. We have previously identified a nonapeptide from the predicted ORFm164 of murine cytomegalovirus that is presented by the MHC-I allomorph H-2 Dd and that is immunodominant in BALB/c (H-2d haplotype) mice. Surprisingly, although the ORFm164 protein gp36.5 is expressed as an Early (E) phase protein, the m164 epitope is presented already during the Immediate Early (IE) phase, based on the expression of an upstream mRNA starting within ORFm167 and encompassing ORFm164.

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Section: Introductionmentioning

confidence: 99%

Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene

Fink

Büttner

Thomas

et al. 2014

Viruses

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“…These inflationary populations also exhibit a highly differentiated membrane phenotype indicative of repeated antigen exposures (14). The adoptive transfer of inflationary MCMV-specific CD8 ϩ T cells into MCMV-infected animals demonstrated these T cells to have a short half-life (45 to 60 days), with their frequency maintained at a high level through the recruitment of naïve and less differentiated T cells into memory through intermittent antigen exposures (14,15). However, the importance of antigen persistence in the generation and maintenance of CMV-specific immunity remains uncertain.…”

mentioning

confidence: 99%

Antiviral Therapy Can Reverse the Development of Immune Senescence in Elderly Mice with Latent Cytomegalovirus Infection

Beswick

Pachnio

Lauder

et al. 2013

J Virol

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b Cytomegalovirus (CMV) infection leads to the development of adaptive and humoral immune responses that are among the largest for any pathogen, and intriguingly, the magnitude of the immune response increases with age, a phenomenon termed "memory inflation." Elevated CMV-specific immunity has been correlated with an increased mortality rate in elderly individuals and with impaired vaccination responses. The latent phase of CMV infection is characterized by intermittent episodes of subclinical viral reactivation and the production of immunogenic transcripts that may maintain memory inflation of virus-specific cytotoxic lymphocytes. However, the relative importance of CMV reactivation in the development of memory inflation is uncertain, as is the potential for antiviral treatment to reverse this effect. Here, we administered valaciclovir for up to 12 months in mice with established murine CMV (MCMV) infection. Treatment reduced the magnitude of the MCMV-specific CD8 ؉ T-lymphocyte response by 80%, and the residual MCMV tetramer-specific lymphocytes exhibited a less differentiated phenotype. In addition, latent MCMV infection suppressed the proportion of naïve CD8 ؉ T cells by 60% compared to antiviral-treated mice or MCMV-negative animals. Furthermore, treatment led to a reduction in influenza A viral loads following a challenge in elderly MCMV-infected animals and also reduced the differentiation of influenza virus-specific cytotoxic lymphocytes. These observations demonstrate that MCMV-specific memory inflation is maintained by viral replication and that therapeutic intervention could lead to improved immune function.

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“…Repeated reactivation of CMV progressively enhances the number of CMV-specific CD8 + T cells, which can accumulate in time up to 20% of total CD8 + T cells, in what is known as “memory inflation” [36]. CD4 + T cells are also expanded with similar kinetics, though to a lesser extent [37].…”

Section: Immune Response To CMVmentioning

confidence: 99%

Evaluation of T Cell Immunity against Human Cytomegalovirus: Impact on Patient Management and Risk Assessment of Vertical Transmission

Freer

Quaranta

Pistello

2016

Journal of Immunology Research

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Cytomegalovirus (CMV) is one of the most common infectious agents, infecting the general population at an early age without causing morbidity most of the time. However, on particular occasions, it may represent a serious risk, as active infection is associated with rejection and disease after solid organ transplantation or fetal transmission during pregnancy. Several methods for CMV diagnosis are available on the market, but because infection is so common, careful selection is needed to discriminate primary infection from reactivation. This review focuses on methods based on CMV-specific T cell reactivity to help monitor the consequences of CMV infection/reactivation in specific categories of patients. This review makes an attempt at discussing the pros and cons of the methods available.

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CMV and the Art of Memory Maintenance

Cited by 17 publications

References 11 publications

Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene

Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene

Antiviral Therapy Can Reverse the Development of Immune Senescence in Elderly Mice with Latent Cytomegalovirus Infection

Evaluation of T Cell Immunity against Human Cytomegalovirus: Impact on Patient Management and Risk Assessment of Vertical Transmission

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