Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

Royston, Léna; Isnard, Stéphane; Lin, John; Routy, Jean Pierre

doi:10.3390/v13071266

Cited by 15 publications

(21 citation statements)

References 85 publications

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“…The results presented also highlight the relevance of considering the heterogeneity of CMV seropositivity and aging in the design of clinical trials or new vaccines in some clinical conditions such in HIV patients. Thus, CMV-induced chronic immune activation and premature immunosenescence in people living with HIV must be taken into consideration not only when comparing trial outcomes between various populations exhibiting diverse CMV positivity rates but also for HIV vaccine development [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Functional Changes of T-Cell Subsets with Age and CMV Infection

Hassouneh

Goldeck

Pera

et al. 2021

IJMS

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Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57− T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.

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Section: Discussionmentioning

confidence: 99%

Functional Changes of T-Cell Subsets with Age and CMV Infection

Hassouneh

Goldeck

Pera

et al. 2021

IJMS

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“… 35 Nevertheless, CMV infection, through induction of inflammation, is believed to participate in immune aging, including decreased response to vaccine. 36 , 37 …”

Section: Latent By Not Silent CMV Coinfection In Plwh Receiving Artmentioning

confidence: 99%

“… 42 , 43 By skewing the immune system and persistently stimulating immune cells, CMV contributes to the inflammaging and notably a decreased response to vaccines. 36 …”

Section: Latent By Not Silent CMV Coinfection In Plwh Receiving Artmentioning

confidence: 99%

“…35 Nevertheless, CMV infection, through induction of inflammation, is believed to participate in immune aging, including decreased response to vaccine. 36,37 In immunocompetent individuals, CMV infects monocytes and establishes latency in a small subset of pluripotent CD34 + hematopoietic stem cells in the bone marrow. 38 In parallel to a true latent stage, asymptomatic CMV reactivation also occurs and spreads in various tissues, including in epithelial cells from the gastrointestinal tract.…”

Section: Bdg As a Marker Of Fungal Transloca-tion Non-aids Comorbidit...mentioning

confidence: 99%

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Aging With Grace for People Living With HIV: Strategies to Overcome Leaky Gut and Cytomegalovirus Coinfection

Routy

Royston

Isnard

2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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: The intestinal epithelial layer acts as a mechanical and functional barrier between the intraluminal microbiota and the immunologically active submucosa. A progressive loss of gut barrier function (leaky gut) leads to enhanced translocation of microbial products, which in turn contributes as endotoxins to inflammaging. Th17 T cell represents the main immune sentinels in the gut epithelium, preventing aggression from commensal and pathogenic microbes. As HIV infection deeply affects gut Th17 function and increases gut permeability, microbial translocation occurs at high level in people living with HIV (PLWH) and has been associated with the development of non-AIDS comorbidities. Although the inflammatory role of endotoxins like lipopolysaccharide produced by Gram-negative bacteria is well-established, fungal products such as β-D-glucan emerge as new contributors. In addition, PLWH are more frequently infected with cytomegalovirus (CMV) than the general population. CMV infection is a well-described accelerator of immune aging, through the induction of expansion of dysfunctional CD8 T-cells as well as through enhancement of gut microbial translocation. We critically review immune mechanisms related to bacterial and fungal translocation, with a focus on the contribution of CMV coinfection in PLWH. Improving gut barrier dysfunction, microbial composition, and reducing microbial translocation constitute emerging strategies for the prevention and treatment of HIV-associated inflammation and may be relevant for age-related inflammatory conditions.

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“…Even if this interaction is still elusive and additional large scale studies are recommended (16), CMV testing and treatment should be taken into consideration in such critical conditions (18). CMV status must be taken into account for several vaccine responses, especially cancer despite the use of HCMV-based therapeutic cancer vaccines (20), since it has been suggested that with advanced age and due to CMV-associated altered immunity in both healthy and immunocompromised hosts, vaccine immunogenicity was modulated (21)(22)(23). Thus, recent studies are concerned about targeting HCMV to decrease the sensitivity to other infectious diseases and cancer, and to prevent poor responses to vaccination (21,22).…”

Section: Introductionmentioning

confidence: 99%

Immune Landscape of CMV Infection in Cancer Patients: From “Canonical” Diseases Toward Virus-Elicited Oncomodulation

Baba

Herbein

2021

Front. Immunol.

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Human Cytomegalovirus (HCMV) is an immensely pervasive herpesvirus, persistently infecting high percentages of the world population. Despite the apparent robust host immune responses, HCMV is capable of replicating, evading host defenses, and establishing latency throughout life by developing multiple immune-modulatory strategies. HCMV has coexisted with humans mounting various mechanisms to evade immune cells and effectively win the HCMV-immune system battle mainly through maintaining its viral genome, impairing HLA Class I and II molecule expression, evading from natural killer (NK) cell-mediated cytotoxicity, interfering with cellular signaling, inhibiting apoptosis, escaping complement attack, and stimulating immunosuppressive cytokines (immune tolerance). HCMV expresses several gene products that modulate the host immune response and promote modifications in non-coding RNA and regulatory proteins. These changes are linked to several complications, such as immunosenescence and malignant phenotypes leading to immunosuppressive tumor microenvironment (TME) and oncomodulation. Hence, tumor survival is promoted by affecting cellular proliferation and survival, invasion, immune evasion, immunosuppression, and giving rise to angiogenic factors. Viewing HCMV-induced evasion mechanisms will play a principal role in developing novel adapted therapeutic approaches against HCMV, especially since immunotherapy has revolutionized cancer therapeutic strategies. Since tumors acquire immune evasion strategies, anti-tumor immunity could be prominently triggered by multimodal strategies to induce, on one side, immunogenic tumor apoptosis and to actively oppose the immune suppressive microenvironment, on the other side.

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Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

Cited by 15 publications

References 85 publications

Functional Changes of T-Cell Subsets with Age and CMV Infection

Functional Changes of T-Cell Subsets with Age and CMV Infection

Aging With Grace for People Living With HIV: Strategies to Overcome Leaky Gut and Cytomegalovirus Coinfection

Immune Landscape of CMV Infection in Cancer Patients: From “Canonical” Diseases Toward Virus-Elicited Oncomodulation

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