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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 co...
Source: Medical Microbiology and Immunology - April 18, 2019 Category: Microbiology Source Type: research

Function of the cargo sorting dileucine motif in a cytomegalovirus immune evasion protein
AbstractAs an immune evasion mechanism, cytomegaloviruses (CMVs) have evolved proteins that interfere with cell surface trafficking of MHC class-I (MHC-I) molecules to tone down recognition by antiviral CD8 T cells. This interference can affect the trafficking of recently peptide-loaded MHC-I from the endoplasmic reticulum to the cell surface, thus modulating the presentation of viral peptides, as well as the recycling of pre-existing cell surface MHC-I, resulting in reduction of the level of overall MHC-I cell surface expression. Murine cytomegalovirus (mCMV) was paradigmatic in that it led to the discovery of this immune...
Source: Medical Microbiology and Immunology - April 18, 2019 Category: Microbiology Source Type: research

Impact of CMV upon immune aging: facts and fiction
AbstractAging is accompanied by significant defects in immunity and compromised responses to new, previously unencountered microbial pathogens. Most humans carry several persistent or latent viruses as they age, interacting with the host immune systems for years. In that context maybe the most studied persistent virus is Cytomegalovirus, infamous for its ability to recruit very large T cell responses which increase with age and to simultaneously evade elimination by the immune system. Here we will address how lifelong CMV infection and the immunological burden of its control might affect immune reactivity and health of the...
Source: Medical Microbiology and Immunology - April 18, 2019 Category: Microbiology Source Type: research

The hallmarks of CMV-specific CD8 T-cell differentiation
AbstractUpon cytomegalovirus (CMV) infection, large T-cell responses are elicited that remain high or even increase over time, a phenomenon named memory T-cell inflation. Besides, the maintained robust T-cell response, CMV-specific T cells seem to have a distinctive phenotype, characterized by an advanced differentiation state. Here, we will review this “special” differentiation status by discussing the cellular phenotype based on the expression of CD45 isoforms, costimulatory, inhibitory and natural killer receptors, adhesion and lymphocyte homing molecules, transcription factors, cytokines and cytotoxic molecules. In...
Source: Medical Microbiology and Immunology - April 12, 2019 Category: Microbiology Source Type: research

Impact of cytomegalovirus load on host response to sepsis
AbstractThere is a decades old association between cytomegalovirus reactivation and sepsis in immune-competent hosts. Much has been learned about this relationship, which has been described as bidirectional, meaning that the virus incites and is incited by the host ’s inflammatory response. More recent work has suggested that chronic viral infection leaves the host with exaggerated immunity to bacterial infections. In this review, the relationship between CMV and host responses to sepsis are reviewed, with particular attention to the impact that tissue viral load contributes to this phenomenon. (Source: Medical Microbiology and Immunology)
Source: Medical Microbiology and Immunology - April 10, 2019 Category: Microbiology Source Type: research

Serum cytokine and chemokine changes during Toscana virus meningitis
AbstractToscana virus is an important arbovirus causing meningitis and meningoencephalitis in countries around the Mediterranean Sea. While the clinical syndrome and laboratory diagnostic procedures have been well described, less is known about the immune response in Toscana virus meningitis and a possible use of cytokine and chemokine changes for the clinical follow-up of patients. We here characterized serum cytokine and chemokine profiles from 37 patients during the acute and convalescent phase of the infection. Only few serum cytokine/chemokine changes were detected during Toscana virus meningitis. Markedly increased c...
Source: Medical Microbiology and Immunology - April 10, 2019 Category: Microbiology Source Type: research

Cytomegalovirus memory inflation and immune protection
AbstractCytomegalovirus (CMV) infection induces powerful and sustained T-cell responses against a few selected immunodominant antigenic epitopes. This immune response was named memory inflation, because it does not contract in the long term, and may even expand over months and years of virus latency. It is by now understood that memory inflation does not occur at the expense of the na ïve T-cell pool, but rather as a competitive selection process within the effector pool, where viral antigens with higher avidity of TCR binding and with earlier expression patterns outcompete those that are expressed later and bind TCRs les...
Source: Medical Microbiology and Immunology - April 9, 2019 Category: Microbiology Source Type: research

Effect of latent cytomegalovirus infection on the antibody response to influenza vaccination: a systematic review and meta-analysis
In conclusion, by systematically integrating the available studies, we show that there is no unequivocal evidence that latent CMV infection affects the influenza antibody response to vaccination. Further studies, including the level of CMV antibodies, are required to settle on the potential influence of latent CMV infection on the influenza vaccine response. (Source: Medical Microbiology and Immunology)
Source: Medical Microbiology and Immunology - April 3, 2019 Category: Microbiology Source Type: research

CD4 T cells are required for maintenance of CD8 T RM cells and virus control in the brain of MCMV-infected newborn mice
AbstractCytomegalovirus (CMV) infection is a significant public health problem. Congenital CMV infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and sensorineural hearing loss. Immune protection against mouse cytomegalovirus (MCMV) is primarily mediated by NK cells and CD8+ T cells, while CD4+ T cells are not needed for control of MCMV in majority of organs in immunocompetent adult mice. Here, we set out to determine the role of CD4+ T cells upon MCMV infection of newborn mice. We provide evidence that CD4+ T cells are essential for clearance of MCMV infection in...
Source: Medical Microbiology and Immunology - March 27, 2019 Category: Microbiology Source Type: research

Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades ’ résumé
AbstractCytomegaloviruses (CMVs) are highly prevalent herpesviruses, characterized by strict species specificity and the ability to establish non-productive latent infection from which reactivation can occur. Reactivation of latent human CMV (HCMV) represents one of the most important clinical challenges in transplant recipients secondary to the strong immunosuppression. In addition, HCMV is the major viral cause of congenital infection with severe sequelae including brain damage. The accumulated evidence clearly shows that cellular immunity plays a major role in the control of primary CMV infection as well as establishmen...
Source: Medical Microbiology and Immunology - March 27, 2019 Category: Microbiology Source Type: research

Kinetics of inflammatory biomarkers in plasma predict the occurrence and features of cytomegalovirus DNAemia episodes in allogeneic hematopoietic stem cell transplant recipients
AbstractCytomegalovirus (CMV) DNAemia occurs frequently in CMV-seropositive allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, and usually results from reactivation of latent infection established in the recipient. Predicting the occurrence of CMV DNAemia may be helpful in managing CMV infection in allo-HSCT recipients. Here, the kinetics of several inflammatory biomarkers in plasma were characterized and assessed for their potential value in anticipating the development and features of active CMV infection in allo-HSCT recipients, as documented using real-time PCR assays. The cohort consisted of 46 non-...
Source: Medical Microbiology and Immunology - March 24, 2019 Category: Microbiology Source Type: research

Seroprevalence of hepatitis E virus (HEV) in a general adult population in Northern Norway: the Troms ø study
AbstractHepatitis E virus (HEV) is a major cause of acute viral hepatitis in many parts of the world but only a few cases have been diagnosed in Norway. To investigate the HEV exposure rate in a presumed low-risk area, we have conducted a population-based study of anti-HEV IgG seroprevalence in Northern Norway. A total of 1800 serum samples from 900 women and 900 men, age 40 –79 years, were randomly selected from the 21,083 participants in the 7th Tromsø Study, representing the 32,591 inhabitants of the Tromsø municipality that were ≥ 40 years. All samples were analyzed by ELISA-1 (recomWell HEV IgG). Samples tes...
Source: Medical Microbiology and Immunology - March 21, 2019 Category: Microbiology Source Type: research

T-cell aging in end-stage renal disease: an evolving story with CMV
AbstractEstablished evidence from the last decade has suggested that chronic cytomegalovirus infection has strong impact on the human immune system, resulting in aggravated aging-associated T-cell changes that are associated with poorer vaccination responses, cardiovascular disease and shortened survival. Patients with end-stage renal disease (ESRD), the most severe form of chronic kidney disease, exhibit premature aging phenotypes in almost all organ systems, including the immune system. Longitudinal studies of T-cell aging in healthy humans have been scanty because it requires a large number of study subjects and a study...
Source: Medical Microbiology and Immunology - March 20, 2019 Category: Microbiology Source Type: research

Emerging roles of cytomegalovirus-encoded G protein-coupled receptors during lytic and latent infection
AbstractCytomegaloviruses (CMVs) have developed multiple diverse strategies to ensure their replicative success and to evade immune recognition. Given the fact that G protein-coupled receptors (GPCRs) are key regulators of numerous cellular processes and modify a variety of signaling pathways, it is not surprising that CMVs and other herpesviruses have hijacked mammalian GPCRs during their coevolution. Human cytomegalovirus (HCMV) encodes for four viral GPCR homologues (vGPCRs), termed US27, US28, UL33, and UL78. Although HCMV-encoded GPCRs were first described in 1990, the pivotal functions of these viral receptor protein...
Source: Medical Microbiology and Immunology - March 20, 2019 Category: Microbiology Source Type: research

Vaccine vectors: the bright side of cytomegalovirus
AbstractCytomegaloviruses (CMVs) present singular features that are particularly advantageous for human vaccine development, a current medical need. Vaccines that induce neutralizing antibodies are among the most successful and efficacious available. However, chronic and persistent human infections, pathogens with high variability of exposed proteins, as well as tumors, highlight the need for developing novel vaccines inducing strong and long-lasting cellular immune responses mediated by effector or effector memory CD8+ cytotoxic T lymphocytes. CMVs induce the most potent CD8+ T lymphocyte response to a pathogen known in e...
Source: Medical Microbiology and Immunology - March 20, 2019 Category: Microbiology Source Type: research