Human type-I interferon omega holds potent antiviral properties and promotes cytolytic CD8+T cell responses

Human type-I interferon omega holds potent antiviral properties and promotes cytolytic CD8+ T cell responses | bioRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Human type-I interferon omega holds potent antiviral properties and promotes cytolytic CD8 + T cell responses Hoang Oanh Nguyen , Patricia Recordon-Pinson , Marie-Line Andreola , Laura Papagno , View ORCID Profile Victor Appay doi: https://doi.org/10.1101/2025.02.13.638030 Hoang Oanh Nguyen 1 Université de Bordeaux, CNRS, INSERM , ImmunoConcEpT, UMR 5164, Bordeaux, France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Patricia Recordon-Pinson 2 Université de Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité , UMR 5234, Bordeaux, France 3 Université de Bordeaux, TBMCore UAR 3427 , UB’L3 facility, Bordeaux, France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marie-Line Andreola 2 Université de Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité , UMR 5234, Bordeaux, France 3 Université de Bordeaux, TBMCore UAR 3427 , UB’L3 facility, Bordeaux, France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Laura Papagno 1 Université de Bordeaux, CNRS, INSERM , ImmunoConcEpT, UMR 5164, Bordeaux, France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Victor Appay 1 Université de Bordeaux, CNRS, INSERM , ImmunoConcEpT, UMR 5164, Bordeaux, France Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Victor Appay For correspondence: victor.appay{at}immuconcept.org Abstract Full Text Info/History Metrics Preview PDF Abstract The type-I interferon family is well known for its critical role in innate immunity. It comprises several members, among which IFN-α2 and IFN-β are the most extensively studied, with important antiviral and immune-modulatory functions. Recent findings linking autoantibodies against type-I interferons to severe COVID-19 suggest a potential role for IFN-ω in combating SARS-CoV-2 infection. However, little is known about human IFN-ω, as most research on this interferon has been conducted in feline models. Here, we demonstrate that human IFN-ω is secreted at levels comparable to those of IFN-α2 or IFN-β upon stimulation with inflammatory agonists and triggers a robust antiviral response, inhibiting SARS-CoV-2 infection in vitro . Moreover, IFN-ω enhances the effector functions of antigen-specific CD8 + T cells primed de novo from healthy donor cells, highlighting its capacity to promote strong cellular immunity. Our results position IFN-ω as a key member of the type-I interferon family, with promising potential for therapeutic and vaccine applications. Author Summary Type-I interferons are pleiotropic cytokines, including IFN-α and IFN-β, which are well known for their antiviral activities. Here, we report on the functional characteristics of human IFN-ω, a neglected member of the type-I IFN family, which has primarily been studied in feline models. We show here that human IFN-ω induces intense downstream signaling in cells resulting in the upregulation of antiviral genes, and efficient restriction of SARS-CoV-2 replication. IFN-ω also promotes the acquisition of strong cytolytic functions by antigen primed CD8 + T cells. Overall, our findings portray human IFN-ω as a major antiviral molecule, similar to the well-studied and highly effective IFN-α 2 . The secretion of IFN-ω upon infection is likely to be crucial for effective control of multiple viruses, advocating for its use in therapeutic approaches in humans. Introduction Type-I interferons (IFNs-I) are known for their striking antiviral capacity 1 and role in regulating both innate and adaptive immune responses 2 . These cytokines can interfere at many levels of the viral replication cycle within cells, thereby preventing viral infection and propagation 3 , 4 . Hence, IFNs-I have been the center of interest in many therapeutic applications and preventive medicine 5 , 6 . The human IFNs-I family comprises up to 16 members, including IFN-α and its many subtypes, IFN-β, IFN-ε, IFN-κ and IFN-ω. All share a relatively homologous structure and bind to the ubiquitously expressed transmembrane receptor composed of two chains, IFNAR1 and IFNAR2 7 , although with different affinities. IFN-α 2 and IFN-β have strong affinity for IFNAR, in contrast to IFN-ε, which has a reduced affinity for the IFNAR2 receptor chain and thus a weaker activity 8 . Upon binding to their cognate receptors, IFNs-I activate the canonical JAK/STAT1/IRF9 cascade, which in turn upregulate a large network of Interferon-stimulated genes (ISGs). These genes orchestrate distinct biological functions of IFNs-I that were thoroughly described based on the characteristics of the prototypical IFN-α 2 and IFN-β 3 , 4 . To date, little research has been conducted on IFN-ω. This interferon, discovered in 1985 by Hauptmann et al 9 , has been identified in humans and several animal species, but not in mice. IFN-ω was thus mainly characterized in feline, where it displays strong anti-viral efficacy 10 - 13 . Hence, recombinant feline IFN-ω has been registered and widely prescribed for the treatment of viral infections in cats in many European countries 14 . However, its functional properties and potential therapeutic benefits have been poorly investigated in the human setting. Recombinant IFN-ω was shown to be well tolerated in HCV infected patients and efficiently reduce HCV RNA levels when combined with ribavirin 15 - 17 . A recent study suggests a role of IFN-ω against SARS-CoV-2 infection in children and young adults 18 . Moreover, high levels of auto-antibodies against IFN-ω have been reported to be associated with high mortality rate in severe COVID-19 patients 19 , 20 . These studies support a potential role of IFN-ω against virus infections in humans and call for an in-depth characterization of its antiviral properties in a human setting. Here we compared the properties of IFN-ω with those of IFN-α 2 across several assays to assess its antiviral and immunomodulatory potency using human cell lines and PBMCs. Results Human monocytes and plasmacytoid DCs produce high levels of IFN-ω We first aimed to assess the bioavailability of IFN-ω. To this end, we stimulated human PBMCs with different proinflammatory agents that mimic virus-induced activation, and measured the secretion of IFN-ω in comparison with IFN-α 2 and IFN-β after 24 hours. We used cGAMP and CpG-A, the ligands for STING and TLR9 respectively, known to induce strong IFN-I responses. For comparison, we also used the TLR4 and TLR8 agonists, LPS and ssRNA40, which induce strong inflammatory but weak IFN responses. Both cGAMP and CpG-A stimulation yielded high levels of IFN-ω, in comparable range to IFN-α 2 and IFN-β. ( Figure 1A ). On the other hand, ssRNA40 was capable of inducing the production of IFN-β and IFN-ω, but not that of IFN-α 2 . As expected, LPS elicited little to no secretion of all types of IFN-Is. Download figure Open in new tab Figure 1. Monocytes and plasmacytoid dendritic cells are the principal source of IFN-ω A . Secretion of IFN-α, IFN-β and IFN-ω by human PBMCs (n=13) upon stimulation with either cGAMP (10 μg/ml), LPS (100 ng/ml), ssRNA40 (500 ng/ml) or CpG-A (2 μg/ml) for 24 hours. Levels of type-I IFNs (α, β, ω) were quantified by ELISA in cell-free supernatants. Each dot represents one donor. B . Levels of IFN-α, IFN-β and IFN-ω in the supernatants of human PBMCs (n=5) depleted for CD19 + B cells, CD14 + monocytes, or CD304 + pDCs, upon stimulation with either cGAMP (10 μg/ml) or CpG-A (2 μg/ml) for 24 hours. Each dot represents one donor. Horizontal bars indicate median value. Differences between groups were tested using the non-parametric Mann Whitney test. To investigate which cell types were responsible for IFN-ω production, we selectively depleted CD14 + monocytes, CD304 + plasmacytoid dendritic cells (pDCs) or CD19 + B cells from total PBMCs and subsequently stimulated the remaining cells with cGAMP or CpG-A. pDCs and monocytes are known to be the main producers of IFN-α upon stimulation with CpG-A and cGAMP respectively 21 . Depletion of monocytes resulted in the loss of IFN-ω secretion in response to cGAMP, whereas depletion of pDCs resulted in the loss of IFN-ω secretion in response to CpG-A ( Figure 1B ). Accordingly, simultaneous depletion of these two populations completely abrogated IFN-ω production with either CpG-A or cGAMP. Similar observations were made for IFN-α and IFN-β production. In contrast, the depletion of B cells did not affect IFNs-I levels. Monocytes and pDCs are therefore the main source of IFN-ω production, which is determined by the type of ligands used for stimulation. The profile and levels of IFN-ω production are similar to those of IFN-α and IFN-β making IFN-ω equivalent to its two sister molecules in terms of bioavailability. IFN-ω induces the STAT1/IRF9 pathway and has potent antiviral activity We next investigated downstream signaling and antiviral activity of IFN-ω. A dual reporter Jurkat cell line was used to study signaling through NF-kB and IRF pathways simultaneously in the presence of different IFNs-I or Poly I:C, a TLR3L ligand, used as positive control. All tested IFNs-I, except the low affinity binder IFN-ε, induced expression of SEAP reporter protein, indicating activation of the STAT1/IRF9 pathway ( Figure 2A ). In contrast, NF-kB signaling remained inactive as low levels of Lucia reporter protein were observed in the presence of IFNs-I. In dose response assays, IFN-ω performed as efficiently as IFN-α 2 or IFN-β in inducing the IRF pathway ( Figure 2B ). These results indicate that IFN-ω binds to IFNARs with high affinity, thus activating efficiently the classic IFN/IRF pathway. Since antiviral activity is a distinctive characteristic of IFNs-I, we explored whether IFN-ω displays similar antiviral potencies as to IFN-α 2 . To this end, we monitored the kinetic expression of mRNAs encoding for proteins associated with the cellular antiviral response, including MX1, OSA2, ISG15, IFI27, IFI2 and MX2, in Calu-3 cells, a pulmonary human cell line, upon exposure to IFN-ω 22 . Significant upregulation of these genes was observed in the presence of IFN-ω, similarly to IFN-α 2, while IFN-ε triggered no antiviral gene profile ( Figure 2C ). Download figure Open in new tab Figure 2. IFN-ω triggers a strong antiviral program in human cells A . Induction of IRF and NF-κB signaling pathways in human cells by type-I IFNs. The Jurkat-Dual™ cell line was stimulated with the TLR3 ligand Poly(I:C) at 5 µg/ml or different IFNs-I (α 1 , α 2, α 6, β, ε or ω) at 100ng/ml for 24 hours. IRF or NF-κB activation was evaluated by measuring the levels of SEAP and Lucia luciferase in cell-free supernatants using QUANTI-Blue™ Solution or Luc™ respectively. Data are expressed as the mean ± SEM of the optical density values of SEAP (left y axis) and Lucia levels (right y axis) from three independent experiments. B . IRF activation was evaluated by measuring the levels of SEAP in supernatants of Jurkat-Dual™ cells after 24h stimulation with IFN-α 2 , β or ω at indicated concentrations. C . Expression of mRNAs encoding proteins associated with the cellular antiviral response in Calu-3 cells at different times upon exposure to IFN-α 2 , ε or ω (100 ng/ml). RNA expression levels were evaluated by Real-Time PCR. Data are expressed as mean ± SEM (n = 3) of 2 −ΔCt relative to housekeeping mRNA (HPRT). D . Cellular morphology of uninfected or SARS-CoV-2 infected Calu-3 cells (MOI = 0.1) in the absence or in the presence of type-I IFNs (100 ng/ml) using an electron microscope. E . Quantification of SARS-CoV-2 replication in Calu-3 cells pre-treated with the indicated doses of IFN-α 2 , ε or ω for 16 hours and infected with SARS-CoV-2 (MOI = 0.1) for 2 hours. Viral suspension was then replaced with medium alone (left panel) or medium containing the respective IFNs (right panel). Viral RNA copies were quantified using RT-PCR. Data are expressed as the mean ± SEM of viral RNA copies from two independent experiments. We next set up a viral infection model by infecting Calu-3 cells with SARS-CoV-2. Calu-3 cells were treated with different concentrations (0.1, 10, 100 ng/ml) of IFN-ω, IFN-α 2 or IFN-ε for 16 hours before viral infection to ensure that both early and late ISGs would be fully induced 22 . Where indicated, the cells were maintained with IFNs-I after the addition of viral suspension. The antiviral effect of IFN-ω was assessed based on Calu-3 morphology and viral replication after infection. Pretreatment with IFN-ω efficiently protected Calu-3 cells against SARS-CoV-2 invasion, characterized by a preserved cell morphology ( Figure 2D ) and low levels of viral RNA copies ( Figure 2E ). The continual presence of IFN-ω at high dose (100 ng/ml) before and after the infection fully inhibited SARS-CoV-2 replication. Of note, IFN-α 2 outperformed IFN-ω in preventing viral replication, at low doses (i.e. 0.1 ng/ml). In contrast, IFN-ε presented minimal to no suppressive effects on SARS-CoV-2 infected Calu-3 cells, consistent with its previously reported weak antiviral characteristic 23 - 25 . The findings indicate that the interaction of IFN-ω with IFNARs induces intense downstream signaling along with high antiviral profile defined by the upregulation of MX1 and OSA2 mRNA levels, similarly as to IFN-α 2 , resulting in efficient restriction of SARS-CoV-2 replication and protection of Calu-3 cells from cytopathic effects. IFN-ω possesses therefore potent antiviral properties and its secretion upon infection is likely crucial for effective viral clearance. IFN-ω bridges innate and adaptive immunity by potentiating the effector functions of antigen-primed CD8 + T cells IFN-α 2 and IFN-β are essential for the differentiation of naive CD8 + T cells into effector cells by tuning a complex network of STAT molecules, including STAT4, whose expression is positively associated with optimal cell expansion and function, and STAT1, which is associated with antiviral genes and cell inhibition 26 , 27 , 28 . We thus compared the phosphorylated forms of STAT4 and STAT1 in subsets of CD8 + T cells treated with IFN-ω, IFN-α 2 or IFN-β. For these experiments, a concentration of 100 ng/ml of IFNs-I was used, as this dose yielded the strongest signaling response. Upon stimulation with IFNs-I, STAT1 and STAT4 were rapidly induced in naive and memory CD8 + T cells and the activation patterns of both pSTATs overlapped between the three IFNs-I over time ( Figure 3A ) . These data demonstrate that IFN-ω resembles IFN-α 2 in terms of STAT regulation and that both STAT1 and STAT4 phosphorylation occur concurrently following IFNs-I exposure. Download figure Open in new tab Figure 3. IFN-ω triggers STAT1 and STAT4 activation and enhances effector functions of antigen primed CD8 + T cells A . STAT1 and STAT4 phosphorylation in CD8 + T cell subsets stimulated with type-I IFNs. pSTAT1 and pSTAT4 were assessed by flow cytometry in naive (CCR7 + CD45RA + ) or memory (non CCR7 + CD45RA + ) CD8 + T cells within human PBMCs exposed to IFN-α 2 , β, or ω (at 100 ng/ml) for indicated times. Representative histograms of pSTAT1 and pSTAT4 in CD8 + T cell subsets treated with IFN-ω for different times are shown, along with data for all three type-I IFNs on two donor PBMCs. B . Representative flow cytometry plots showing tetramer + CD8 + T-cells expanded for 10 days upon priming from HLA-A2 donor PBMCs with Melan-A (ELA) peptide (1 µg/ml) alone or in the presence of IFN-α 2 , β, or ω (at 100 ng/ml) (left upper panel) and frequencies of ELA-specific CD8 + T cells for 11 donors (lower panel). C . Representative flow cytometry plots showing T-bet, Granzyme B and Perforin expression in ELA tetramer + CD8 + T cells (upper panel). The dotted line shows the limit for positive expression. Percentage of T-bet, Granzyme B and Perforin positive ELA-specific CD8 + T cells (lower panel). Each dot represents one donor (n=11). Horizontal bars indicate median value. Differences between groups were tested using the non-parametric Mann Whitney test. We then investigated the effect of IFN-ω on the induction of an antigen-specific CD8 + T cell response from naive lymphocytes using an in vitro model of T cell priming. The Melan-A peptide (ELA) was used as a model antigen owing to the high frequency of specific naive CD8 + T cell precursors identified in PBMCs from HLA-A*0201 + (HLA-A2 + ) individuals, which can be readily primed in vitro from unfractionated PBMCs 29 . This assay enables us to evaluate the effects of IFN-ω on the expansion and functional properties of antigen-specific CD8 + T cells 10 days after priming. The expansion of ELA tetramer + CD8 + T cells was rather reduced in the presence of IFN-β and IFN-α 2 , but not IFN-ω ( Figure 3B ). IFNs-I, especially IFN-ω, significantly increased the expression of the transcriptional factor T-bet, known to promote CD8 + T cell effector functions, such as the secretion of IFN-γ ( Figure 3C ). Moreover, significantly higher levels of the cytotoxins Granzyme B and Perforin were observed in the presence of IFNs-I ( Figure 3C ). Therefore, IFN-ω appears particularly potent at promoting the acquisition of effector functions by CD8 + T cells upon priming, without blunting their expansion. These data indicate that IFN-ω can contribute to the induction of strong cytolytic CD8 + T cell responses in the context of viral infections. Discussion Altogether, our findings indicate that human IFN-ω is produced by monocytes or pDCs at levels comparable to those of IFN-α 2 or IFN-β, and can contribute significantly to the first line of defense against viral infections, as well as the induction of potent antiviral CD8 + T cell responses. The biological properties of human IFN-ω closely resemble those of IFN-α 2 , including its antiviral activities and immunostimulatory effects. Considering the critical role of IFN-α 2 or IFN-β in clinical practice, IFN-ω could therefore be considered an important candidate in immunotherapies. Although IFN-ω shares 62% and 33% of its amino acid sequence with IFN-α 2 and IFN-β respectively, antibodies specific for these two IFNs-I do not cross-react with IFN-ω 30 , 31 . IFN-ω represents therefore an interesting secondary option for patients who are resistant to IFN-α 2 or IFN-β due to the formation of autoantibodies during treatment 32 . The lack of in vivo mouse models has slowed the development of therapeutic applications using IFN-ω. However, the presence of IFN-ω reduced the production of HbeAg and HBV-DNA synthesis by half in human HBV infected hepatoma cells 33 . Furthermore, IFN-ω appeared to be more potent than IFN-α 2 in suppressing influenza infection in A549 cell line 34 . Recombinant human IFN-ω was also capable of subduing mRNA levels of HPV11 E6 in the HaCaT cell line 35 . Taken together, these data imply that IFN-ω could exert important antiviral effects on a variety of viruses, not limited to retroviruses as demonstrated in feline models. The study of IFN-ω in clinical trials for the treatment of viral infections should be a priority. Materials and methods (Detailed protocols are provided in supporting information) Cells and viruses PBMCs were obtained from healthy volunteers attending the Etablissement Français du Sang. Jurkat dual cells were obtained from Invivogen and Calu-3 cells from the ATCC. The SARS-CoV-2 strain BetaCoV/France/IDF0372/2020 was supplied by the National Reference Centre for Respiratory Viruses. Cytokine quantification and flow cytometry IFNs-I were detected using specific ELISA kits (Mabtech and eBioscience). For phosphoflow assays, cells were stained with anti-STAT1-AF647 and anti-STAT4-PE (BD Biosciences). In vitro priming of antigen-specific CD8 + T cells was performed as described previously 36 . Data were acquired using an LSR Fortessa (BD Biosciences) and analyzed with FlowJo (Tree Star Inc.). Statistical Analysis Statistical significance was determined using unpaired T-test with Mann-Whitney (GraphPad Software). Funding This research was funded by the University of Bordeaux (Senior IdEx Chair) and by a grant of the Region Nouvelle Aquitaine. The funders had no role in the design of the review, collection, analysis, interpretation of the literature, nor in the writing or the decision to submit this review for publication. Author Contributions Conceptualization, V.A., L.P., H.O.N; methodology, V.A., H.O.N, P.P., M-L.A.; investigation and data curation, H.O.N., P.P.; writing—original draft preparation, H.O.N., writing—review and editing, V.A., L.P., P.P., M-L.A; visualization, H.O.N and P.P.; supervision, V.A.; funding acquisition, V.A. All the authors have read and agreed to the published version of the manuscript. Abbreviations IFN Interferon IFNs-I Type-I Interferons HBV Hepatitis B virus HCV Hepatitis C virus ISGs Interferon-stimulated genes TCR T cell receptor pDCs plasmacytoid dendritic cells SARS-COV2 Severe acute respiratory syndrome coronavirus 2 STAT1 Signal transducer and activator of transcription 1 STAT4 Signal transducer and activator of transcription 4 PBMCs Peripheral blood mononuclear cells PDL1 programmed cell death 1 ligand rFeIFN recombinant feline Interfon rhIFN recombinant human IFN Availability of data and materials The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author. Conflicts of Interest The authors declare that they have no competing financial interests Acknowledgements We thank all donors for participating in this study. We grateful to David Price and Sian Sian Llewellyn-Lacey from Cardiff University School of Medicine, Cardiff CF14 4XN, UK for providing peptide-MHC tetramer reagents, and to Atika Zouine and Vincent Pitard for technical assistance at the Flow cytometry facility, CNRS UMS 3427, INSERM US 005, Univ. Bordeaux, F-33000 Bordeaux, France. Footnotes Antiviral potency of human type-I interferon omega References 1. ↵ Isaacs A , Lindenmann J. Virus interference. I. The interferon . Proc R Soc Lond B Biol Sci . Sep 12 1957 ; 147 ( 927 ): 258 – 67 . doi: 10.1098/rspb.1957.0048 OpenUrl CrossRef PubMed 2. ↵ Bencze D , Fekete T , Pázmándi K. Type I Interferon Production of Plasmacytoid Dendritic Cells under Control . Int J Mol Sci . Apr 18 2021 ; 22 ( 8 ) doi: 10.3390/ijms22084190 OpenUrl CrossRef 3. ↵ Samuel CE . Antiviral actions of interferons . Clin Microbiol Rev . 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Share Human type-I interferon omega holds potent antiviral properties and promotes cytolytic CD8 + T cell responses Hoang Oanh Nguyen , Patricia Recordon-Pinson , Marie-Line Andreola , Laura Papagno , Victor Appay bioRxiv 2025.02.13.638030; doi: https://doi.org/10.1101/2025.02.13.638030 Share This Article: Copy Citation Tools Human type-I interferon omega holds potent antiviral properties and promotes cytolytic CD8 + T cell responses Hoang Oanh Nguyen , Patricia Recordon-Pinson , Marie-Line Andreola , Laura Papagno , Victor Appay bioRxiv 2025.02.13.638030; doi: https://doi.org/10.1101/2025.02.13.638030 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Immunology Subject Areas All Articles Animal Behavior and Cognition (7622) Biochemistry (17648) Bioengineering (13870) Bioinformatics (41880) Biophysics (21423) Cancer Biology (18553) Cell Biology (25458) Clinical Trials (138) Developmental Biology (13364) Ecology (19866) Epidemiology (2067) Evolutionary Biology (24290) Genetics (15589) Genomics (22475) Immunology (17711) Microbiology (40327) Molecular Biology (17145) Neuroscience (88472) Paleontology (666) Pathology (2826) Pharmacology and Toxicology (4815) Physiology (7635) Plant Biology (15114) Scientific Communication and Education (2044) Synthetic Biology (4286) Systems Biology (9815) Zoology (2268)