Type I IFN – A blunt spear in fighting HIV-1 infection

Acchioni, Chiara; Marsili, Giulia; Perrotti, Edvige; Remoli, Anna Lisa; Sgarbanti, Marco; Battistini, Angela

doi:10.1016/j.cytogfr.2014.10.004

Cited by 24 publications

(27 citation statements)

References 168 publications

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“…Particularly, all analyses highlighted the significant effect of IFN-α genes on chronic immune activation, accounting for the evidence of the involvement of the IFN-α pathway reported in chronic immune activation in successfully treated HIV-1-infected patients [10–12]. …”

Section: Discussionmentioning

confidence: 99%

“…The persistence of immune activation is associated with both acquired immunodeficiency syndrome (AIDS) and non-AIDS comorbidities [3–6] in patients under successful antiretroviral therapy with long-term virological suppression. Noteworthy, chronic type I alpha-interferon (IFN-α) is a hallmark in chronic activation and has been reported as a factor influencing disease progression in persistent infections [7–9], including HIV [10–12]. The mechanisms driving chronic immune activation and type I interferon secretion are multifactorial and are not completely understood [13].…”

Section: Introductionmentioning

confidence: 99%

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Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV Patients

Picat¹,

Pellegrin²,

Bitard³

et al. 2017

PLoS ONE

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ObjectivesTo unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes.DesignCross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France.MethodsPatients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years. CIA was defined by the percentage of HLA-DR+/CD38+ among CD8+T-cells. Integrative analyses were performed using structural equation modelling (SEM).ResultsThe main analysis was performed in 57 HLA-A*0201 positive patients, due to availability of percentages of actin-, vimentin-, lamin-specific CD8+T-cells (HLA-A2-restricted tests) to further characterize autoimmune response. Cytomegalovirus-induced response was assessed by Quantiferon and pp-65 ELISPOT. SEM revealed a direct effect of cytomegalovirus-induced response on CIA (standardized estimate βstd = 0.56, p-value = 0.0004). The effect of autoimmune-induced response on CIA was indirect through alpha-interferon pathway, assessed by expression levels of 5 alpha-interferon-stimulated genes ADAR, ISG15, IFIT1, Mx1 and OAS1 (effect of autoimmune response on alpha-interferon: βstd = 0.36, p-value = 0.0401; effect of alpha-interferon on CIA: βstd = 0.39, p-value = 0.0044). There was no direct effect of autoimmune-induced response on CIA (p-value = 0.3169). Microbial translocation as measured by 16SrDNA and sCD14 in plasma was not associated with CIA. Results were consistent in 142 patients in whom cytomegalovirus and auto-immunity responses were measured by Quantiferon and anti-nuclear antibodies, respectively. All analyses performed in HLA-A*0201 positive patients and in the overall population revealed a significant effect of IFN-α latent variable on CIA.ConclusionThe role of cytomegalovirus-induced response on CIA was confirmed as well as the involvement of alpha-interferon on CIA. The indirect effect of auto-immunity response on CIA revealed through the alpha-interferon pathway requires further investigation to confirm the potential role of auto-immunity for CIA in HIV-infected patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV Patients

Picat¹,

Pellegrin²,

Bitard³

et al. 2017

PLoS ONE

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“…HIV-1 has, indeed, developed a number of strategies to block the IFN signaling and the activity of IFN-induced host restriction factors. Here, we only briefly summarize these strategies some of which have been only recently discovered, leading to the identification of immune pathways, thus far, unrecognized (as recently reviewed elsewhere [114][115][116][117][118][119][120]).…”

Section: Hiding Detection And/or Interfering With Sensor Pathwaysmentioning

confidence: 99%

“…To increase virus replication and establish viral persistence and latency, HIV-1, besides to dismantle or exploit almost all cell intrinsic innate recognition pathways, as discussed above, also directly hits IRFs [113,119,169].…”

Section: Evasion/subversion Of Downstream Prr Signaling: Ikks and Irfsmentioning

confidence: 99%

“…Although the first antiviral ISGs were discovered decades ago, until recently the mechanisms of action was defined for only a limited number of ISG-encoded proteins. The renewed interest in the innate immune response to retroviruses with the identification of how several host restriction factors may limit retroviral infection [118][119][120], as well as large-scale functional screening of ISGs, have identified genes that coordinately control the infection of a range of RNA and DNA viruses and have begun to dissect their mechanism of action [153,216]. Interestingly, some of the most potent antiviral effectors reinforce the system by further inducing IFN or ISGs.…”

Section: Interfering With Isgsmentioning

confidence: 99%

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Early IFN type I response: Learning from microbial evasion strategies

Coccia

Battistini

2015

Seminars in Immunology

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Type I interferon (IFN) comprises a class of cytokines first discovered more than 50 years ago and initially characterized for their ability to interfere with viral replication and restrict locally viral propagation. As such, their induction downstream of germ-line encoded pattern recognition receptors (PRRs) upon recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark of the host antiviral response. The acknowledgment that several PAMPs, not just of viral origin, may induce IFN, pinpoints at these molecules as a first line of host defense against a number of invading pathogens. Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. On the other hand an inverse interference to escape the IFN system is largely exploited by pathogens through a number of tactics and tricks aimed at evading, inhibiting or manipulating the IFN pathway, that result in progression of infection or establishment of chronic disease. In this review we discuss the interplay between the IFN system and some selected clinically important and challenging viruses and bacteria, highlighting the wide array of pathogen-triggered molecular mechanisms involved in evasion strategies.

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