@article{john_smith_istishin_mahmood_diveley_tollison_carpenter_peng_2025, title={<i>VILMIR</i> is a <i>trans</i> -acting long noncoding RNA that enhances the host interferon response in human epithelial cells}, volume={12}, url={https://doi.org/10.1128/jvi.01380-25}, DOI={10.1128/jvi.01380-25}, abstractNote={Long noncoding RNAs (lncRNAs) have been found to play significant regulatory roles within antiviral and immune responses. We previously identified the novel lncRNA virus-inducible lncRNA modulator of interferon response (<i>VILMIR</i>), which was found to broadly regulate the host transcriptional response to interferon-beta (IFN-β) treatment in A549 human lung epithelial cells. Here, we investigated the mechanism by which <i>VILMIR</i> regulates the host interferon response in <i>trans</i> by identifying interacting proteins and gene regulatory networks of <i>VILMIR</i>. Through an RNA pull-down assay, we found that <i>VILMIR</i> interacted with both nuclear and cytoplasmic proteins <i>in vitro</i>, including the transcriptional regulators FUBP1 and PUF60 in the nucleus, as well as the antiviral proteins IFIT1 and IFIT3 and the aminoacyl-tRNA synthetases QARS1 and KARS1 in the cytoplasm. In addition, we found that the overexpression of <i>VILMIR</i> in A549 cells resulted in an overall enhancement of host interferon response genes and identified a core set of interferon-stimulated genes that were consistently regulated by <i>VILMIR</i> knockdown and overexpression. Finally, we proposed several possible mechanisms by which <i>VILMIR</i> may interact with the identified proteins to regulate the interferon response, such as by interacting with FUBP1 and PUF60 in the nucleus to regulate host transcription in <i>trans</i> or by interacting with the IFIT proteins and aminoacyl-tRNA synthetases in the cytoplasm to regulate translation.IMPORTANCEDespite thousands of long noncoding RNAs (lncRNAs) being differentially expressed after immune responses and viral infections, there is limited knowledge on their individual functions in these contexts. We previously identified a novel lncRNA, <i>VILMIR</i>, that was found to be an interferon-stimulated gene that regulated the host transcriptional response to interferon-beta treatment in human epithelial cells. Here, we investigated the mechanism by which <i>VILMIR</i> regulates the interferon response. Through <i>in vitro</i> studies, we identified several nuclear and cytoplasmic proteins that interact with <i>VILMIR</i>, including proteins involved in transcriptional and translational regulation. In addition, we demonstrated that the overexpression of <i>VILMIR</i> results in an enhancement of host interferon response genes, supporting our hypothesis that <i>VILMIR</i> plays an activating role in the host interferon response. Finally, we propose several potential models for the mechanism of <i>VILMIR</i>, providing a foundation for the investigation of <i>VILMIR</i> as a novel therapeutic target in antiviral immunity.}, journal={Journal of Virology}, author={John, Kristen and Smith, Ethan and Istishin, Alexandra and Mahmood, Nasif and Diveley, Kayleigh and Tollison, Tammy S. and Carpenter, Susan and Peng, Xinxia}, editor={Gallagher, TomEditor}, year={2025}, month={Dec} }
 @article{john_huntress_smith_chou_tollison_covarrubias_crisci_carpenter_peng_2025, title={Human long noncoding RNA <i>VILMIR</i> is induced by major respiratory viral infections and modulates the host interferon response}, volume={3}, url={https://doi.org/10.1128/jvi.00141-25}, DOI={10.1128/jvi.00141-25}, abstractNote={Long noncoding RNAs (lncRNAs) are a newer class of noncoding transcripts identified as key regulators of biological processes. Here, we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic data sets. Using bulk RNA-sequencing (RNA-seq) analysis, we identified a previously uncharacterized lncRNA, named virus-inducible lncRNA modulator of interferon response (<i>VILMIR</i>), that was consistently upregulated after <i>in vitro</i> influenza infection across multiple human epithelial cell lines and influenza A virus subtypes. <i>VILMIR</i> was also upregulated after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) infections <i>in vitro</i>. We experimentally confirmed the response of <i>VILMIR</i> to influenza infection and interferon-beta (IFN-β) treatment in the A549 human epithelial cell line and found the expression of <i>VILMIR</i> was robustly induced by IFN-β treatment in a dose- and time-specific manner. Single-cell RNA-seq analysis of bronchoalveolar lavage fluid samples from coronavirus disease 2019 (COVID-19) patients uncovered that <i>VILMIR</i> was upregulated across various cell types, including at least five immune cells. The upregulation of <i>VILMIR</i> in immune cells was further confirmed in the human T cell and monocyte cell lines, SUP-T1 and THP-1, after IFN-β treatment. Finally, we found that knockdown of <i>VILMIR</i> expression reduced the magnitude of host transcriptional responses to both IFN-β treatment and influenza A virus infection in A549 cells. Together, our results show that <i>VILMIR</i> is a novel interferon-stimulated gene (ISG) that regulates the host interferon response and may be a potential therapeutic target for human respiratory viral infections upon further mechanistic investigation.IMPORTANCEIdentifying host factors that regulate the immune response to human respiratory viral infection is critical to developing new therapeutics. Human long noncoding RNAs (lncRNAs) have been found to play key regulatory roles during biological processes; however, the majority of lncRNA functions within the host antiviral response remain unknown. In this study, we identified that a previously uncharacterized lncRNA, virus-inducible lncRNA modulator of interferon response (<i>VILMIR</i>), is upregulated after major respiratory viral infections including influenza, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus. We demonstrated that <i>VILMIR</i> is an interferon-stimulated gene that is upregulated after interferon-beta (IFN-β) in several human cell types. We also found that knockdown of <i>VILMIR</i> reduced the magnitude of host transcriptional responses to IFN-β treatment and influenza A infection in human epithelial cells. Our results reveal that <i>VILMIR</i> regulates the host interferon response and may present a new therapeutic target during human respiratory viral infections.}, journal={Journal of Virology}, author={John, Kristen and Huntress, Ian and Smith, Ethan and Chou, Hsuan and Tollison, Tammy S. and Covarrubias, Sergio and Crisci, Elisa and Carpenter, Susan and Peng, Xinxia}, editor={Gallagher, TomEditor}, year={2025}, month={Mar} }
 @article{mora-navarro_smith_wang_ramos-alamo_collins_awad_cruz_tollison_huntress_gartling_et al._2026, title={Injection of vocal fold lamina propria-derived hydrogels modulates fibrosis in injured vocal folds}, volume={178}, ISSN={2772-9508}, url={http://dx.doi.org/10.1016/j.bioadv.2025.214424}, DOI={10.1016/j.bioadv.2025.214424}, abstractNote={Vocal fold (VF) fibrosis, often resulting from phonosurgery, radiation, or trauma, causes irreversible voice dysfunction due to excessive ECM deposition and increased tissue stiffness. No FDA-approved treatments for VF fibrosis exist, highlighting the need for novel antifibrotic therapies. TGF-β1 contributes to fibroblast-to-myofibroblast activation, leading to increased ACTA2 expression and collagen production via SMAD3, YAP1, and integrin signaling pathways. Leveraging the principle that local cells respond to tissue-specific signals, our ECM hydrogel, derived from decellularized vocal fold lamina propria (VFLP-ECM), reduced ACTA2 expression in TGF-β1-stimulated VF fibroblasts, showcasing antifibrotic potential. This study evaluates the therapeutic potential of VFLP-ECM hydrogel in a rabbit VF injury model. VFLP-ECM hydrogel or bovine type I collagen injections were administered 7 days post-injury and evaluated on day 28. We compared two VFLP-ECM formulations: a manual process (VFLP (man)) and an accelerated automated method (VFLP (au)). VFLP (man) modulated fibrosis-associated gene expressions more effectively than controls. Proteomics identified 229 proteins uniquely preserved in VFLP (man), including vitronectin, crucial in TGF-β1 signaling and ECM remodeling. Transcriptomic analysis suggests downregulation of fibrotic markers and inhibition of SMAD3, YAP1, and MRTFA, alongside upregulation of SMAD7, an inhibitor of TGF-β signaling. Notably, VFLP (man) treatment recovered stiffness comparable to uninjured controls (1.84 vs. 1.94 mN), whereas collagen-treated tissues remained stiff (2.7 mN), similar to the injury group (2.6 mN), indicating incomplete mechanical recovery. These in vivo data show that manually decellularized VFLP-ECM hydrogel attenuates fibrosis by disrupting key biochemical and mechanical cues driving myofibroblast activation.}, journal={Biomaterials Advances}, publisher={Elsevier BV}, author={Mora-Navarro, Camilo and Smith, Ethan and Wang, Ziyu and Ramos-Alamo, Maria del C. and Collins, Leonard and Awad, Nour and Cruz, Denzel Ryan D. and Tollison, Tammy S. and Huntress, Ian and Gartling, Gary and et al.}, year={2026}, month={Jan}, pages={214424} }