A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity DOI Creative Commons
Fahd Al Qureshah, Jérémie Le Pen, Nicole A. de Weerd

и другие.

The Journal of Experimental Medicine, Год журнала: 2024, Номер 222(2)

Опубликована: Дек. 16, 2024

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, is globally very rare, except for in Western Polynesia Arctic, respectively. We report 11 alleles, products which impair but do not abolish IFN-α -ω without affecting IFN-β. Ten these alleles are rare all populations studied, remaining allele (P335del) common Southern China (minor frequency ≈2%). Cells heterozygous variants display a dominant phenotype vitro with impaired susceptibility. Negative dominance, rather than haploinsufficiency, accounts this dominance. Patients prone attesting both dominance clinically importance protective immunity against some viruses.

Язык: Английский

Prevalence of EBV, HHV6, HCMV, HAdV, SARS-CoV-2, and Autoantibodies to Type I Interferon in Sputum from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients DOI Creative Commons

Ulf Hannestad,

Annika Allard, Kent W. Nilsson

и другие.

Viruses, Год журнала: 2025, Номер 17(3), С. 422 - 422

Опубликована: Март 14, 2025

An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome, also termed long COVID. In this study, potential mechanisms behind exhaustion were investigated. First, the viral load of Epstein–Barr virus (EBV), human adenovirus (HAdV), cytomegalovirus (HCMV), herpesvirus 6 (HHV6), severe acute respiratory coronavirus 2 (SARS-CoV-2) was determined sputum samples (n = 29) derived from ME/CFS patients 13), healthy controls 10), elderly 4), immunosuppressed 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) analyzed possibly explain impaired immunity. We found that released EBV at a significantly higher level compared (p 0.0256). HHV6 present ~50% all participants same level. HAdV detected two cases with immunosuppression ME/CFS, respectively. HCMV SARS-CoV-2 only controls. Notably, anti-IFN-I autoAbs did not differ, except case showing an increased conclude patients, controls, have EBV. IFN-I cannot dysfunction, possible exception cases, reported SARS-CoV-2. forward additional mechanisms, such as evasion effect via degradation IFN-receptors, may be which demands further studies.

Язык: Английский

Процитировано

0
Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design DOI Creative Commons
Kevin Groen,

Roger Kuratli,

Jannik Enkelmann

и другие.

The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(6)

Опубликована: Март 20, 2025

Autoantibodies neutralizing type I interferons (IFN-Is; IFNα or IFNω) exacerbate severe viral disease, but specific treatments are unavailable. With footprint profiling, we delineate two dominant IFN-I faces commonly recognized by autoantibody–containing plasmas from aged individuals with HIV-1 and COVID-19. These overlap regions independently essential for engaging the IFNAR1/IFNAR2 heterodimer, efficiently block interaction of both receptor subunits in vitro. In contrast, non-neutralizing limit only one subunit display relatively low IFN-I–binding avidities, thus likely hindering function. Iterative engineering signaling-inert mutant IFN-Is (simIFN-Is) retaining autoantibody targets created potent decoys that prevent neutralization autoantibody-containing restore IFN-I–mediated antiviral activity. Additionally, microparticle-coupled simIFN-Is were effective at depleting autoantibodies plasmas, leaving antibodies unaffected. Our study reveals mechanisms action demonstrates a proof-of-concept strategy to alleviate pathogenic effects.

Язык: Английский

Процитировано

0
Powassan and other emerging neuroinvasive arboviruses in North America DOI

Reece Hass,

Michel B. Tolédano

Current Opinion in Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Март 30, 2025

Purpose of review Arthropod-borne viruses (arboviruses) represent a group pathogens with increasing global relevance, some which cause neuroinvasive disease. Transmitted by arthropod vectors and maintained variety primary amplifying hosts, epidemics are dependent on numerous environmental anthropogenic factors. This serves to highlight several important arboviruses relevant North America discuss the neurologic presentations, diagnosis, outcomes, future trends. Recent findings shifts in epidemiology ecology include divergence such as dengue chikungunya from dependence enzootic cycles, geographical expansion Oropouche virus, incidence established American Powassan virus. Accurate identification factors contributing arboviral outbreaks is critical improve preventive public health measures. Similarly, further elucidating pathogen host that determine neuroinvasiveness, neurotropism, neurovirulence will be key development successful vaccines targeted therapeutics. Summary Arboviruses an human Familiarity diagnostic workup, treatment strategies, expected course for clinicians caring these patients.

Язык: Английский

Процитировано

0
Human type I interferons protect Vero E6 and ARPE-19 cells against West Nile virus and are neutralized by pathogenic autoantibodies DOI Creative Commons
Alessandro Ferrari, Irene Cassaniti, Francesca Rovida

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 2, 2025

Auto-antibodies (auto-Abs) that neutralize type I interferons (IFNs) have been implicated in severe viral infections, including ~ 40% of cases West Nile virus (WNV) neuroinvasive disease (WNND). Developing robust vitro models to evaluate the protective effects IFNs against infection, as well disruptive auto-Abs, is essential for understanding pathogenesis and identifying patients at risk. In this study, we used Vero E6 ARPE-19 cell lines investigate ability (IFN-α, IFN-β, IFN-ω), II (IFN-γ), III (IFN-λ1) restrict WNV infection. Our results demonstrate IFN-α, IFN-ω effectively protect cells from with IFN-β exhibiting strongest antiviral effect. contrast, required higher concentrations achieve comparable protection. Neither IFN-γ nor IFN-λ1 conferred protection either line. We further screened serum samples WNV-infected auto-Abs neutralizing IFNs. findings confirm ARPE-19-based assay consistent other established methods detecting This simple reliable offers a valuable tool assessing activity both research clinical settings. Future studies should aim validate utility ARPE-19-WNV infection model on larger scale.

Язык: Английский

Процитировано

0
Sterile production of interferons in the thymus DOI
Ryan J. Martinez, Kristin A. Hogquist

The Journal of Immunology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

Abstract T-cell central tolerance is controlled by thymocyte TCR recognition of self-peptides presented thymic APCs. While epithelial cells are essential for tolerance, a variety other traditional APCs also play critical roles in selection. Similar to how peripheral require activation become effective, tolerogenic. Recent studies have identified IFNs as an factor the and generation optimally tolerogenic environment. In this review, we focus on interferon (IFN) production within thymus its effects developing thymocytes. We examine importance IFN itself well interferon-stimulated proteins generated during immune responses.

Язык: Английский

Процитировано

0
Quantifying temporal differences in the induction of interferon-mediated signalling observed in a dengue virus 1 human infection model: insights from longitudinal proteome analysis DOI Creative Commons
Caroline Struyfs, Klaas Van Den Heede, Liesbeth Van Wesenbeeck

и другие.

EBioMedicine, Год журнала: 2025, Номер 115, С. 105728 - 105728

Опубликована: Апрель 26, 2025

Язык: Английский

Процитировано

0
Deciphering the autoreactome: Massively parallelized methods for autoantibody detection in humans DOI
Nicolai Valentin Hörstke, Thomas Vogl

Journal of Immunological Methods, Год журнала: 2025, Номер unknown, С. 113876 - 113876

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Auto-Abs neutralizing type I IFNs in patients with severe Powassan, Usutu, or Ross River virus disease DOI Creative Commons
Adrian Gervais, Paul Bastard, Lucy Bizien

и другие.

The Journal of Experimental Medicine, Год журнала: 2024, Номер 221(12)

Опубликована: Ноя. 1, 2024

Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne (TBE, TBE [TBEV]) (∼10%). We report here that these auto-Abs also severe forms rarer arboviral infections. Auto-Abs high concentrations IFN-α2, IFN-β, and/or IFN-ω present in the single case Powassan (POWV) studied, two three cases Usutu (USUV) infection most 24 Ross River (RRV) disease studied. These not found any 137 individuals with silent or mild infections viruses. Thus, IFNs an increasing list Flaviviridae (WNV, TBEV, POWV, USUV) Togaviridae viruses transmitted humans by mosquitos USUV, RRV) ticks (TBEV, POWV).

Язык: Английский

Процитировано

3
Genetic defects of brain immunity in childhood herpes simplex encephalitis DOI
Shen‐Ying Zhang, Jean‐Laurent Casanova

Nature, Год журнала: 2024, Номер 635(8039), С. 563 - 573

Опубликована: Ноя. 20, 2024

Язык: Английский

Процитировано

3
A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity DOI Creative Commons
Fahd Al Qureshah, Jérémie Le Pen, Nicole A. de Weerd

и другие.

The Journal of Experimental Medicine, Год журнала: 2024, Номер 222(2)

Опубликована: Дек. 16, 2024

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, is globally very rare, except for in Western Polynesia Arctic, respectively. We report 11 alleles, products which impair but do not abolish IFN-α -ω without affecting IFN-β. Ten these alleles are rare all populations studied, remaining allele (P335del) common Southern China (minor frequency ≈2%). Cells heterozygous variants display a dominant phenotype vitro with impaired susceptibility. Negative dominance, rather than haploinsufficiency, accounts this dominance. Patients prone attesting both dominance clinically importance protective immunity against some viruses.

Язык: Английский

Процитировано

0