Immunosenescence and Cytomegalovirus: Exploring Their Connection in the Context of Aging, Health, and Disease

Müller, Ludmila; Di Benedetto, Svetlana

doi:10.3390/ijms25020753

IJMS

2024

DOI: 10.3390/ijms25020753

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Immunosenescence and Cytomegalovirus: Exploring Their Connection in the Context of Aging, Health, and Disease

Ludmila Müller,

Svetlana Di Benedetto

Abstract: Aging induces numerous physiological alterations, with immunosenescence emerging as a pivotal factor. This phenomenon has attracted both researchers and clinicians, prompting profound questions about its implications for health and disease. Among the contributing factors, one intriguing actor in this complex interplay is human cytomegalovirus (CMV), a member of the herpesvirus family. Latent CMV infection exerts a profound influence on the aging immune system, potentially contributing to age-related diseases. … Show more

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Cited by 3 publications

References 168 publications

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Human herpesvirus reactivation and its potential role in the pathogenesis of post-acute sequelae of SARS-CoV-2 infection

Gáspár,

Szabó,

Ceglédi

et al. 2024

GeroScience

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The emergence of SARS-CoV-2 has precipitated a global pandemic with substantial long-term health implications, including the condition known as post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as Long COVID. PASC is marked by persistent symptoms such as fatigue, neurological issues, and autonomic dysfunction that persist for months beyond the acute phase of COVID-19. This review examines the potential role of herpesvirus reactivation, specifically Epstein-Barr virus (EBV) and cytomegalovirus (CMV), in the pathogenesis of PASC. Elevated antibody titers and specific T cell responses suggest recent herpesvirus reactivation in some PASC patients, although viremia is not consistently detected. SARS-CoV-2 exhibits endothelial trophism, directly affecting the vascular endothelium and contributing to microvascular pathologies. These pathologies are significant in PASC, where microvascular dysfunction may underlie various chronic symptoms. Similarly, herpesviruses like CMV also exhibit endothelial trophism, which may exacerbate endothelial damage when reactivated. Evidence suggests that EBV and CMV reactivation could indirectly contribute to the immune dysregulation, immunosenescence, and autoimmune responses observed in PASC. Additionally, EBV may play a role in the genesis of neurological symptoms through creating mitochondrial dysfunction, though direct confirmation remains elusive. The reviewed evidence suggests that while herpesviruses may not play a direct role in the pathogenesis of PASC, their potential indirect effects, especially in the context of endothelial involvement, warrant further investigation.

show abstract

Human herpesvirus reactivation and its potential role in the pathogenesis of post-acute sequelae of SARS-CoV-2 infection

Gáspár,

Szabó,

Ceglédi

et al. 2024

GeroScience

View full text Add to dashboard Cite

show abstract

Long COVID as a disease of accelerated biological aging: An opportunity to translate geroscience interventions

Shafqat,

Masters,

Tripathi

et al. 2024

Ageing Research Reviews

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The Wide Spectrum of Presentations of Cytomegalovirus Infection in Immunocompetent Hosts: An Exhaustive Narrative Review

Schattner

2024

Pathogens

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CMV is a ubiquitous DNA virus that establishes infection and results in 40–100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. However, an extensive review of the literature published up to April 2024 reveals that despite immunocompetence, CMV can cause a very large variety of clinical syndromes in any part of the gastrointestinal tract (the most common pattern), the central or peripheral nervous system, and the eyes, as well as hematological, pulmonary, cardiac, and cutaneous disease. Not uncommonly, more than one system is involved, and though the disease is often self-limited, treatment with intravenous ganciclovir or oral valganciclovir may be required, and in isolated cases, fatalities may occur. Thus, a potential CMV infection should be considered in the differential of myriad syndromes in non-immunocompromised patients. Associated systemic symptoms (fever, sweats, and weight loss), lymphocytosis, and hepatitis are not uncommon and can be a useful clue. Some populations, such as critically ill patients in intensive care, pregnant women, elderly patients, and those with inflammatory bowel disease, may be more susceptible. Moreover, the potential of past, latent CMV infection (i.e., CMV seropositivity) to be associated with significant cardiovascular morbidity and all-cause mortality years later is intriguing and requires further study. All these data indicate the outstanding importance of developing a vaccine against CMV, which hopefully will become available in the foreseeable future. Meanwhile, a solid diagnosis of active CMV infection can be quickly established (or ruled out) by widely available serology tests and PCR amplification, and clinicians in all disciplines need to be more aware of the diverse guises of CMV infection and remember to consider it in any host, including an immunocompetent one.

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Immunosenescence and Cytomegalovirus: Exploring Their Connection in the Context of Aging, Health, and Disease

Cited by 3 publications

References 168 publications

Human herpesvirus reactivation and its potential role in the pathogenesis of post-acute sequelae of SARS-CoV-2 infection

Human herpesvirus reactivation and its potential role in the pathogenesis of post-acute sequelae of SARS-CoV-2 infection

Long COVID as a disease of accelerated biological aging: An opportunity to translate geroscience interventions

The Wide Spectrum of Presentations of Cytomegalovirus Infection in Immunocompetent Hosts: An Exhaustive Narrative Review

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