Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis

Peng, Xiaorong; Isnard, Stéphane; Lin, John; Fombuena, Brandon; Bessissow, Talat; Chomont, Nicolas; Routy, Jean‐Pierre

doi:10.1016/j.jve.2021.100033

Cited by 8 publications

(9 citation statements)

References 18 publications

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“…However, the effect of IFN-a on T cells during persistent infection remains controversial [82]. Studies showed that blocking all signalling through IFNAR was beneficial to T cells; however, it also resulted in higher viral loads and drove the immune activation associated with greater reservoir size [83,84]. Since IFN-a2 is the predominant subtype during HIV-1 infection [30] it may be the primary contributor to deleterious IFNAR signalling.…”

Section: Discussionmentioning

confidence: 99%

Distinct effects of treatment with two different interferon-alpha subtypes on HIV-1-associated T-cell activation and dysfunction in humanized mice

Rout

Dittmer

et al. 2021

Aids

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Objective: Interferon-alpha (IFN-a) has been associated with excessive immune activation and dysfunction during HIV-1 infection. However, evidence suggests specific IFN-a subtypes may be beneficial rather than detrimental. This study compared the effects of treatment with two different IFN-a subtypes on indicators of T-cell activation and dysfunction during HIV-1 infection.Design: Humanized mice were infected with HIV-1 for 5 weeks and then treated with two different IFN-a subtypes for an additional 3 weeks. Splenic T cells were assessed both immediately posttreatment and again 6 weeks after treatment cessation.Methods: HIV-1 infected triple-knockout bone marrow-liver-thymus mice received daily intraperitoneal injections of either IFN-a14 or the clinically approved subtype, IFN-a2. T cells were analysed directly ex vivo for indicators of activation and dysfunction or stimulated to determine their proliferative capacity and ability to produce functional mediators.Results: Unlike IFN-a2, IFN-a14 treatment reduced viremia and resulted in less activated CD4 þ T cells and a lower naı ¨ve to effector CD8 þ T-cell ratio. Despite exhibiting a reduced proliferative response, the frequency of CD8 þ T cells from IFN-a14 treated mice that produced functional mediators and expressed markers of dysfunction was more similar to healthy controls than untreated and IFN-a2 treated mice. Frequencies of exhaustion marker expression remained higher in untreated and IFN-a2 treated mice 6 weeks posttreatment despite similar viral loads between groups at this timepoint.Conclusions: Treatment with different IFN-a subtypes had distinctive effects on T cells during HIV-1 infection. IFN-a14 was associated with fewer indicators of T-cell dysfunction whereas IFN-a2 treatment had little impact.

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Section: Discussionmentioning

confidence: 99%

Distinct effects of treatment with two different interferon-alpha subtypes on HIV-1-associated T-cell activation and dysfunction in humanized mice

Rout

Dittmer

et al. 2021

Aids

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“…However, their effect on CD4 + levels should be assessed (Hunt et al 2021 ). It was also concluded that HIV persistence in UC could be challenged through a strong gut barrier integrity and reduction of inflammation (Peng et al 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review

Zarenezhad

Abdulabbas

Kareem³

et al. 2023

Arch Microbiol

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Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein–Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.

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“…These bacterial and fungal translocations are associated with systemic immune activation and tissue inflammation (109). Cells in inflamed gut tissue are described as having a 27-fold higher frequency of HIV DNA than cells in non-inflamed gut tissue (110). This immune activation and inflammation is thought to lead to an increase in the frequency of other conditions such as metabolic and cardiovascular diseases (111).…”

Section: Intestinal Barrier Functionmentioning

confidence: 99%

Th17 CD4+ T-Cell as a Preferential Target for HIV Reservoirs

et al. 2022

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Among CD4+ T-cells, T helper 17 (Th17) cells play a sentinel role in the defense against bacterial/fungal pathogens at mucosal barriers. However, Th17 cells are also highly susceptible to HIV-1 infection and are rapidly depleted from gut mucosal sites, causing an imbalance of the Th17/Treg ratio and impairing cytokines production. Consequently, damage to the gut mucosal barrier leads to an enhanced microbial translocation and systemic inflammation, a hallmark of HIV-1 disease progression. Th17 cells’ expression of mucosal homing receptors (CCR6 and α4β7), as well as HIV receptors and co-receptors (CD4, α4β7, CCR5, and CXCR4), contributes to susceptibility to HIV infection. The up-regulation of numerous intracellular factors facilitating HIV production, alongside the downregulation of factors inhibiting HIV, helps to explain the frequency of HIV DNA within Th17 cells. Th17 cells harbor long-lived viral reservoirs in people living with HIV (PLWH) receiving antiretroviral therapy (ART). Moreover, cell longevity and the proliferation of a fraction of Th17 CD4 T cells allow HIV reservoirs to be maintained in ART patients.

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Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis

Cited by 8 publications

References 18 publications

Distinct effects of treatment with two different interferon-alpha subtypes on HIV-1-associated T-cell activation and dysfunction in humanized mice

Distinct effects of treatment with two different interferon-alpha subtypes on HIV-1-associated T-cell activation and dysfunction in humanized mice

Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review

Th17 CD4+ T-Cell as a Preferential Target for HIV Reservoirs

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