Variant-Specific tRNA-Derived Fragments Induced by Severe Acute Respiratory Syndrome Coronavirus 2: Implications for Disease Outcome Differentiation

Variant-Specific tRNA-Derived Fragments Induced by Severe Acute Respiratory Syndrome Coronavirus 2: Implications for Disease Outcome Differentiation | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 26 June 2025 V1 Latest version Share on Variant-Specific tRNA-Derived Fragments Induced by Severe Acute Respiratory Syndrome Coronavirus 2: Implications for Disease Outcome Differentiation Authors : Wenzhe Wu , Meagan Rippee-Brooks D , Awadalkareem Adam , Kayleigh Weinstein , Fiyinfoluwa Ola-Daniel , Ke Zhang , Eun-Jin Choi , … Show All … , Devang Deepak , Joshua Fernandez de la Vega , Egide Ishimwe , Gengming Huang , Natalie Williams-Bouyer , Inhan Lee , Patricia Aguilar , Tian Wang , Jianli Dong , and Xiaoyong Bao 0000-0002-6884-2584 [email protected] Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.175093935.52881141/v1 Published Journal of Medical Virology Version of record Peer review timeline 284 views 188 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a critical global health challenge, with many molecular pathogenism mechanisms remaining unclear. Among small noncoding RNAs, tRNA-derived RNA fragments (tRFs) have gained attention for their roles in viral infections. We previously reported significant alterations in tRFs originating from the 5’-end of tRNAs (tRF5s) in nasopharyngeal swab (NPS) specimens from COVID-19 patients infected with the SARS-CoV-2 alpha variant. Building upon this work, we collected 209 NPS specimens between late 2021 and February 2023. This cohort of specimens includes patients positive for delta or omicron variants (BA.1, BA.5, XBB.1.5), and negative controls. We investigated five tRF5s (tRF5-GlnCTG, tRF5-CysGCA, tRF5-ValCAC, tRF5-GlyCCC2, and tRF5-GlyGCC) expression among this cohort and observed distinct tRF5s induction patterns among the different viral variants. tRF5-ValCAC, which we previously reported was induced by the alpha variant, was absent among later variants. tRF5-GlnCTG was consistently elevated by multiple variants (alpha, delta, and BA.1), while the induction diminished in BA.5 and XBB.1.5. tRF5-GlyCCC2 induction had not been observed until the BA.1 wave; its induction initially occurred in the pediatric population with BA.1 or BA.5, and later within both pediatric and adult populations with XBB.1.5. Subsequently, cytokines/chemokines within these NPS specimens were measured via Bio-plex. We found several tRF5s levels correlated with cytokines/chemokines. Functional study results suggested these tRF5s regulate the replication of their corresponding SARS-CoV-2 variants. Our findings highlight a potential link between tRF5s and disease severity, offering insights into their functional roles in viral replication and their potential as biomarkers. Supplementary Material File (sars2_2_manuscript_jmv_final.docx) Download 1.49 MB Information & Authors Information Version history V1 Version 1 26 June 2025 Peer review timeline Published Journal of Medical Virology Version of Record 26 Mar 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords immune responses infection infectious bronchitis virus pathogenesis respiratory tract sars coronavirus virus classification Authors Affiliations Wenzhe Wu The University of Texas Medical Branch at Galveston View all articles by this author Meagan Rippee-Brooks D The University of Texas Medical Branch at Galveston View all articles by this author Awadalkareem Adam The University of Texas Medical Branch at Galveston View all articles by this author Kayleigh Weinstein The University of Texas Medical Branch at Galveston View all articles by this author Fiyinfoluwa Ola-Daniel The University of Texas Medical Branch at Galveston View all articles by this author Ke Zhang The University of Texas Medical Branch at Galveston View all articles by this author Eun-Jin Choi The University of Texas Medical Branch at Galveston View all articles by this author Devang Deepak The University of Texas Medical Branch at Galveston View all articles by this author Joshua Fernandez de la Vega The University of Texas Medical Branch at Galveston View all articles by this author Egide Ishimwe The University of Texas Medical Branch at Galveston View all articles by this author Gengming Huang The University of Texas Medical Branch at Galveston View all articles by this author Natalie Williams-Bouyer The University of Texas Medical Branch at Galveston View all articles by this author Inhan Lee miRcore View all articles by this author Patricia Aguilar The University of Texas Medical Branch at Galveston View all articles by this author Tian Wang The University of Texas Medical Branch at Galveston View all articles by this author Jianli Dong The University of Texas Medical Branch at Galveston View all articles by this author Xiaoyong Bao 0000-0002-6884-2584 [email protected] The University of Texas Medical Branch at Galveston View all articles by this author Metrics & Citations Metrics Article Usage 284 views 188 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Wenzhe Wu, Meagan Rippee-Brooks D, Awadalkareem Adam, et al. Variant-Specific tRNA-Derived Fragments Induced by Severe Acute Respiratory Syndrome Coronavirus 2: Implications for Disease Outcome Differentiation. Authorea . 26 June 2025. DOI: https://doi.org/10.22541/au.175093935.52881141/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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