Current views on interferon therapy for HIV

Rivero‐Juárez, Antonio; Frías, Mario; Rivero, Antonio

doi:10.1080/14712598.2016.1196180

Cited by 11 publications

(5 citation statements)

References 61 publications

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“…We identified IFN-α14 as a more potent in vivo suppressor of HIV-1 infection than IFN-α2 using humanized mice [32], a finding confirmed by others [31,33,34]. Administration of IFN-α2 has been shown to activate CD8 + T cells [35,36] but has had limited success in controlling HIV-1 in clinical trials [37,38]. Evidence also suggests that elevated IFN-α2 may exacerbate hyperactivation, exhaustion and death of T cells [28,32,39–41] whereas IFN-α14 may more potently activate NK cells [32] and prevent CD4 + cell loss [33] without driving the detrimental effects associated with IFN-α2 [32].…”

Section: Introductionsupporting

confidence: 58%

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: Introductionsupporting

confidence: 58%

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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“…At the early phase of infection, the secreted large amounts of type I IFNs have beneficial effects, whereas during the late phase, chronic activation of pDCs results in type I IFN-driven pathologies such as T cell exhaustion, apoptosis of uninfected CD4+ T cells through an increased expression of programmed cell death 1 (PD-1) receptor as well as generation of regulatory T cells via upregulating tolerogenic mediators such as IL-10 or IDO [195][196][197][198]. Based on these data, the clinical usage of type I IFN therapy in HIV-1 infection is quite controversial, since it seems to be beneficial in the acute phase, whereas it is not advised in the chronic phase of infection [199,200]. In spite of this, it is important to note that recombinant human IFNα2b is indicated for the treatment of various human chronic viral infections associated with malignant conditions such as acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma, human papilloma virus (HPV)-caused condyloma acuminata, and chronic hepatitis C (HCV) or hepatitis B (HBV) infections [201][202][203][204].…”

Section: Targeting Type I Ifns In Pdc-related Pathological Conditions 61 Viral Infectionsmentioning

confidence: 99%

Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

Bencze

Fekete

Pázmándi

2021

IJMS

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One of the most powerful and multifaceted cytokines produced by immune cells are type I interferons (IFNs), the basal secretion of which contributes to the maintenance of immune homeostasis, while their activation-induced production is essential to effective immune responses. Although, each cell is capable of producing type I IFNs, plasmacytoid dendritic cells (pDCs) possess a unique ability to rapidly produce large amounts of them. Importantly, type I IFNs have a prominent role in the pathomechanism of various pDC-associated diseases. Deficiency in type I IFN production increases the risk of more severe viral infections and the development of certain allergic reactions, and supports tumor resistance; nevertheless, its overproduction promotes autoimmune reactions. Therefore, the tight regulation of type I IFN responses of pDCs is essential to maintain an adequate level of immune response without causing adverse effects. Here, our goal was to summarize those endogenous factors that can influence the type I IFN responses of pDCs, and thus might serve as possible therapeutic targets in pDC-associated diseases. Furthermore, we briefly discuss the current therapeutic approaches targeting the pDC-type I IFN axis in viral infections, cancer, autoimmunity, and allergy, together with their limitations defined by the Janus-faced nature of pDC-derived type I IFNs.

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“…The expressions of these antiviral genes point toward a natural defense mechanism evolved to protect against viral infections that begin their pathogenesis in the mouth. While these genes, and their protein products, have been previously characterized in other tissues (Schneider et al, ; Schoggins & Rice, ) and even used as therapies for viral infections in general (Galvani, Griffiths, & Cawley, ; Hsu, Chao, Lin, Chen, & Kao, ; Rivero‐Juárez, Frias, & Rivero, ; Smith et al, ), more remains to be studied in OECs, the first cells viruses encounter when orally infecting individuals. Understanding the intricacies of our endogenous type I IFN and ISGs in OECs will eventually lead to targets for either preventative measures or therapies for diseases associated with oral viral infections.…”

Section: Discussionmentioning

confidence: 99%

Type I interferon and interferon‐stimulated gene expression in oral epithelial cells

Brice

Figgins

et al. 2019

Molecular Oral Microbiology

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Oral epithelial cells (OEC) represent the first site of host interaction with viruses that infect the body through the oral route; however, their innate antiviral defense mechanisms yet to be defined. Previous studies have determined that OEC express pathogen‐, damage‐, or danger‐associated molecular patterns (PAMPs or DAMPs), but their expression of key antiviral innate immune mediators, including type I interferons (type I IFN) and interferon‐stimulated genes (ISGs) has not been studied extensively. We used the oral keratinocyte cell line, OKF6/TERT1, in the presence and absence of the viral mimics poly(I:C) and unmethylated CpG DNA, to define the expression of type I IFN and ISGs. We identified the basal expression of novel type I IFN genes IFNE and IFNK, while IFNB1 was induced by viral mimics, through the nuclear translocation of IRF3. Numerous ISGs were expressed at basal levels in OEC, with an apparent correlation between high expression and antiviral activity at the earlier stages of viral infection. Stimulation of OECs with poly(I:C) led to selective induction of ISGs, including MX1, BST2, PML, RSAD2, ISG15, and ZC3HAV1. Together, our results demonstrate that OECs exhibit a robust innate antiviral immune defense profile, which is primed to address a wide variety of pathogenic viruses that are transmitted orally.

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Current views on interferon therapy for HIV

Cited by 11 publications

References 61 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

Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

Type I interferon and interferon‐stimulated gene expression in oral epithelial cells

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