Known unknowns: how might the persistent herpesvirome shape immunity and aging?
Open accessAbstract
The microbial community that colonizes all living organisms is gaining appreciation for its contributions to both physiologic and pathogenic processes. The virome, a subset of the overall microbiome, large and diverse, including viruses that persistently inhabit host cells, endogenous viral elements genomically or epigenomically integrated into cells, and viruses that infect the other (bacterial, protozoan, fungal, and archaeal) microbiome phylla. These viruses live in the organism for its life, and therefore are to be considered part of the aging process experienced by the organism. This review considers the impact of the persistent latent virome on immune aging. Specific attention will be devoted to the role of herpesviruses, and within them, the cytomegalovirus, as the key modulators of immune aging.
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These T cells do not express the co-stimulatory molecule CD28, required for the activation of T cells.
“These T cells do not express the co-stimulatory molecule CD28, required for the activation of T cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.
“Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
The loss of CD28 occurs following cell proliferation, according to the observation that CD28− T cells have shorter telomeres than CD28+ cells.
“The loss of CD28 occurs following cell proliferation, according to the observation that the CD28− T cells have shorter telomeres than CD28+ cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
CD28 seems a good biomarker of immunosenescence, as suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.
“CD28 seems a good biomarker of immunosenescence, as further suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
Senescent T cells are producers of pro-inflammatory cytokines.
“In addition, they are producers of pro-inflammatory cytokines (17, 18, 41–47).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
This determines the phenomenon of memory cell inflation, leading to the emergence of vast populations of resting effector CD8+ and, to a lesser extent, CD4+ cells.
“As previously stated, this determines the phenomenon of memory cell inflation, leading to the emergence of vast populations of resting effector CD8+ and, to a lesser extent, CD4+ cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
In the latent state, the intermittent production of viral antigens prevents contraction of virus-specific T cells.
“In the latent state, the intermittent production of viral antigens prevents contraction of virus-specific T cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
These inflated HCMV-specific memory T cells maintain their efficient effector functions for the lifetime of the individual.
“These inflated HCMV-specific memory T cells maintain their efficient effector functions for the lifetime of the individual (40, 46, 52).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
In older people, one or a few clonal populations can occupy more than 25% of the entire CD8+ cell pool.
“In older people, one or a few clonal populations can occupy more than 25% of the entire CD8+ cell pool (46, 51).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
Inflationary CD8+ cells, after proper activation stimuli, can divide, secrete cytokines, and execute cytolysis, i.e., they are not exhausted.
“Inflationary CD8+ cells, after proper activation stimuli, can divide, secrete cytokines, and execute cytolysis, i.e., they are not exhausted.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [46]
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- Authors
- Nikolich-Zugich, J., Goodrum, F., Knox, K., & Smithey, M. J.
- Affiliations
- University of Arizona (US)
- Corresponding author
- Smithey, Megan J
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 48
- Pages
- 23-30
- ISSN
- 0952-7915 (ISSN-L)
- PMC
- PMC5682194
- OpenAlex
- W2742380604
- Cited by
- 51
- References
- 69
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 11 · 2018: 6
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 AG048021, N01-AI-000017)
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Keywords
- immunosenescence, cytomegalovirus, herpesvirus, endogenous viral elements, virome, microbiome, host-virus interaction
- MeSH terms
- Aging, Animals, Cytomegalovirus, Herpesviridae, Herpesviridae Infections, Humans, Virus Integration, Virus Latency, Immunomodulation, Microbiota
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