Effect of cytomegalovirus and Epstein–Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals

The restoration of CD4+ T cells, especially T-helper type 17 (Th17) cells, remains incomplete in the gut mucosa of most human immunodeficiency virus type 1 (HIV-1)–infected individuals despite sustained antiretroviral therapy (ART). Herein, we report an increase in the absolute number of CXCR3+ T cells in the duodenal mucosa during ART. The frequencies of Th1 and CXCR3+ CD8+ T cells were increased and negatively correlated with CCL20 and CCL25 expression in the mucosa. In ex vivo analyses, we showed that interferon γ, the main cytokine produced by Th1 and effector CD8+ T cells, downregulates the expression of CCL20 and CCL25 by small intestine enterocytes, while it increases the expression of CXCL9/10/11, the ligands of CXCR3. Interleukin 18, a pro-Th1 cytokine produced by enterocytes, also contributes to the downregulation of CCL20 expression and increases interferon γ production by Th1 cells. This could perpetuate an amplification loop for CXCR3-driven Th1 and effector CD8+ T cells recruitment to the gut, while impairing Th17 cells homing through the CCR6-CCL20 axis in treated HIV-1–infected individuals.

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“…Mucosal reactivation of CMV in the gut could also be an important driver of T cell activation [25,26].…”

Section: Discussionmentioning

confidence: 99%

Increased CXCR3+ T Cells Impairs Recruitment of T-Helper Type 17 Cells via Interferon γ and Interleukin 18 in the Small Intestine Mucosa During Treated HIV-1 Infection

Loiseau

Requena²,

Nayrac

et al. 2019

The Journal of Infectious Diseases

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“…In HIV patients, CMV infection can cause retinitis (in 80% of cases), gastrointestinal manifestations (in 10 to 15% of cases), colitis, esophagitis, hepatitis, encephalitis, myeloradiculopathy, and lung involvement (1-5% of cases) [ 39 ]. Moreover, both CMV and EBV are frequently detected in the intestinal mucosa of HIV patients and might lead to local and systemic inflammation [ 40 ].…”

Section: Clinical Manifestations Of CMV and Ebv Infectionsmentioning

confidence: 99%

Cytomegalovirus and Epstein-Barr Infections: Prevalence and Impact on Patients with Hematological Diseases

Silva

Pinheiro-Silva

Dhyani

et al. 2020

BioMed Research International

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Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are widely distributed throughout the world. EBV is linked to various hematological and autoimmune disorders whereas CMV might play important role in the progression of chronic hematological diseases, such as hemoglobinopathies, lymphomas, myelomas, hemophilia, and aplastic and sickle cell anemia. Both viruses produce a viral homolog of human interleukin-10 that can cause general suppression of immune response, increasing susceptibility to other infections. These viruses can remain latent in the host cells and be reactivated when the host immune system is compromised. Studies showing the impact of CMV and EBV infections on hematological disorders are scarce and unclear in the context of coinfection. This review intends to present the biology, prevalence, and impact of CMV and EBV infections in patients with hematological diseases.

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“…CMV, independent of HIV, results in the tight junction disruption as treatment with letermovir, an anti-CMV drug, dampens the effects of CMV on the gut by restoring the epithelia [87]. As such, CMV infection may be associated with certain aberrations in gut microbiome profiles [88]. A recent longitudinal study found that gut colonisation by Staphylococcus aureus was protective against early acquisition of CMV infection [89].…”

Section: Gut Microbiome Profilesmentioning

confidence: 99%

Epidemiology of Cytomegalovirus among pregnant women in Africa

Mhandire

Rowland‐Jones

Mhandire

et al. 2019

J Infect Dev Ctries

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Introduction: Vertical transmission of Cytomegalovirus (CMV), resulting in congenital CMV (cCMV) infection could have disabling and potentially fatal effects on the foetus or neonate. Although primary infection probably has a higher risk of leading to cCMV, in highly seropositive populations, a significant risk of vertical transmission is thought to be due to CMV reactivation and or reinfection during pregnancy. In this narrative review, we summarise the prevalence of CMV infection and associated risk factors among pregnant African women, in a setting where primary CMV infection usually occurs during infancy. Methodology: A systematic search of literature published between January 2000 and January 2019, retrieved on five bibliographic databases was performed. Search for relevant articles was performed using the following keywords: cytomegalovirus, CMV, infection, antenatal infections, pregnancy, pregnant women, gravidity, developing countries and Africa, with appropriate qualifiers such as OR, AND. Results: Systematic searching retrieved 11 relevant original research papers. Prevalence of anti-CMV IgG and IgM antibodies ranged from 60-100% and 0-15.5%, respectively. Prevalence of CMV DNA ranged from 0-29%, depending on the specimen used. However, there was no geographic trend for CMV seroprevalence or CMV DNA prevalence across the African continent. Overall, a substantial percentage of women of reproductive-age were CMV seronegative and at risk of primary infection. Associations of sociodemographic factors with CMV infection were inconsistent across all reviewed studies. Conclusions: The limited data and inconsistency of findings from the few studies carried out in Africa calls for prospective studies comparing prevalence and outcomes of cCMV in infants born to women with both primary and reactivated CMV in Africa.

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Effect of cytomegalovirus and Epstein–Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals

Cited by 30 publications

References 44 publications

Increased CXCR3+ T Cells Impairs Recruitment of T-Helper Type 17 Cells via Interferon γ and Interleukin 18 in the Small Intestine Mucosa During Treated HIV-1 Infection

Increased CXCR3+ T Cells Impairs Recruitment of T-Helper Type 17 Cells via Interferon γ and Interleukin 18 in the Small Intestine Mucosa During Treated HIV-1 Infection

Cytomegalovirus and Epstein-Barr Infections: Prevalence and Impact on Patients with Hematological Diseases

Epidemiology of Cytomegalovirus among pregnant women in Africa

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