Cytomegalovirus Infection in Cardiovascular Diseases

Lebedeva, A.; Shpektor, A.; Vasilieva, Elena; Margolis, Leonid

doi:10.1134/s0006297918120027

Cited by 27 publications

(21 citation statements)

References 101 publications

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“…As the effects of CMV might be related to specific chronic conditions and not to a general health state such as frailty, we investigated the association of CMV infection with cardiovascular disease (CVD). Indeed, in line with previous studies, 52,53 the prevalence of CVD was significantly higher in CMV + individuals. Furthermore, within CMV + individuals, prevalence of CVD was associated with higher CMV-specific antibody levels at endpoint.…”

Section: Discussionsupporting

confidence: 92%

Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27‐year‐long longitudinal study

et al. 2020

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Objectives Cytomegalovirus infection is thought to affect the immune system and to impact general health during ageing. Higher CMV‐specific antibody levels in the elderly are generally assumed to reflect experienced viral reactivation during life. Furthermore, high levels of terminally differentiated and CMV‐specific T cells are hallmarks of CMV infection, which are thought to expand over time, a process also referred to as memory inflation. Methods We studied CMV‐specific antibody levels over ~ 27 years in 268 individuals (aged 60–89 years at study endpoint), and to link duration of CMV infection to T‐cell numbers, CMV‐specific T‐cell functions, frailty and cardiovascular disease at study endpoint. Results In our study, 136/268 individuals were long‐term CMV seropositive and 19 seroconverted during follow‐up (seroconversion rate: 0.56%/year). CMV‐specific antibody levels increased slightly over time. However, we did not find an association between duration of CMV infection and CMV‐specific antibody levels at study endpoint. No clear association between duration of CMV infection and the size and function of the memory T‐cell pool was observed. Elevated CMV‐specific antibody levels were associated with the prevalence of cardiovascular disease but not with frailty. Age at CMV seroconversion was positively associated with CMV‐specific antibody levels, memory CD4 + T‐cell numbers and frailty. Conclusion Cytomegalovirus‐specific memory T cells develop shortly after CMV seroconversion but do not seem to further increase over time. Age‐related effects other than duration of CMV infection seem to contribute to CMV‐induced changes in the immune system. Although CMV‐specific immunity is not evidently linked to frailty, it tends to associate with higher prevalence of cardiovascular disease.

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Section: Discussionsupporting

confidence: 92%

Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27‐year‐long longitudinal study

et al. 2020

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“…While it is well established that cytokine secretion during both chronic and acute inflammatory proceses is a hallmark of CVD, in particular of STEMI, a potential etiological agent that could have triggered such immunoactivation was not determined. Several publications indicate that different infections, in particular, activated cytomegalovirus could be such an agent [74][75][76][77] . It has now to be established whether the cytokines belonging to the clusters identified in the present work contribute to STEMI and what are the main triggers of their secretion.…”

Section: Discussionmentioning

confidence: 99%

Differential clusterization of soluble and extracellular vesicle-associated cytokines in myocardial infarction

Lebedeva

Fitzgerald

Molodtsov

et al. 2020

Sci Rep

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A proinflammatory dysregulation of cytokine release is associated with various diseases, in particular with those of infectious etiology, as well as with cardiovascular diseases (CVD). We showed earlier that cytokines are released in two forms, soluble and in association with extracellular vesicles (EVs). Here, we investigated the patterns of expression and clustering of soluble and EV-associated cytokines in patients with ST-elevation myocardial infarction (STEMI). We collected plasma samples from 48 volunteers without CVD and 62 patients with STEMI, separated soluble and EV fractions, and analyzed them for 33 cytokines using a multiplexed bead-based assay. We identified soluble and EV-associated cytokines that are upregulated in STEMI and form correlative clusters. Several clustered soluble cytokines were expressed almost exclusively in patients with STEMI. EV-associated cytokines were largely not affected by STEMI, except for pro-inflammatory cytokines IL-6, IL-18, and MIG, as well as anti-inflammatory IL-2 that were upregulated in a correlated fashion. Our results demonstrated that soluble cytokines in patients with STEMI are upregulated in a coordinated fashion in contrast to the mainly unaffected system of EV-associated cytokines. Identification of cytokine clusters affected differently by STEMI now permits investigation of their differential contributions to this pathology.

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“…Interestingly, the frequency of detection of CMV DNA or antigenemia is significantly higher in patients with atopic dermatitis and periodontitis (Docke et al, 2003;Chalabi et al, 2008). It is well-established that CMV accelerates atherosclerosis, both in cardiac transplant patients and in animal models of transplantation, and CMV infection is a suspected etiologic agent in cardiovascular disease and mortality in the population at large (Streblow et al, 2008;Simanek et al, 2011;Kaminski and Fishman, 2016;Wang et al, 2017;Lebedeva et al, 2018).…”

Section: Reactivation Of Naturally Acquired Hcmv Infectionmentioning

confidence: 99%

Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response

Forte

Zhang

Thorp

et al. 2020

Front. Cell. Infect. Microbiol.

152

103

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CMV is an ancient herpesvirus that has co-evolved with its host over millions of years. The 236 kbp genome encodes at least 165 genes, four non-coding RNAs and 14 miRNAs. Of the protein-coding genes, 43-44 are core replication genes common to all herpesviruses, while ∼30 are unique to betaherpesviruses. Many CMV genes are involved in evading detection by the host immune response, and others have roles in cell tropism. CMV replicates systemically, and thus, has adapted to various biological niches within the host. Different biological niches may place competing demands on the virus, such that genes that are favorable in some contexts are unfavorable in others. The outcome of infection is dependent on the cell type. In fibroblasts, the virus replicates lytically to produce infectious virus. In other cell types, such as myeloid progenitor cells, there is an initial burst of lytic gene expression, which is subsequently silenced through epigenetic repression, leading to establishment of latency. Latently infected monocytes disseminate the virus to various organs. Latency is established through cell type specific mechanisms of transcriptional silencing. In contrast, reactivation is triggered through pathways activated by inflammation, infection, and injury that are common to many cell types, as well as differentiation of myeloid cells to dendritic cells. Thus, CMV has evolved a complex relationship with the host immune response, in which it exploits cell type specific mechanisms of gene regulation to establish latency and to disseminate infection systemically, and also uses the inflammatory response to infection as an early warning system which allows the virus to escape from situations in which its survival is threatened, either by cellular damage or infection of the host with another pathogen. Spontaneous reactivation induced by cellular aging/damage may explain why extensive expression of lytic genes has been observed in recent studies using highly sensitive transcriptome analyses of cells from latently infected individuals. Recent studies with animal models highlight the potential for harnessing the host immune response to blunt cellular injury induced by organ transplantation, and thus, prevent reactivation of CMV and its sequelae.

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Cytomegalovirus Infection in Cardiovascular Diseases

Cited by 27 publications

References 101 publications

Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27‐year‐long longitudinal study

Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27‐year‐long longitudinal study

Differential clusterization of soluble and extracellular vesicle-associated cytokines in myocardial infarction

Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response

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