{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T20:35:47Z","timestamp":1769718947169,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Platelets have traditionally been viewed as passive cellular elements involved in hemostasis and vascular integrity. However, growing evidence over the last decade has radically changed this paradigm, revealing platelets as dynamic immune and inflammatory effectors that actively participate in host\u2013pathogen interactions. In viral infections, platelets are not merely innocent bystanders but represent key players in a bidirectional and tightly regulated platelet\u2013virus axis that influences viral dissemination, immune activation, endothelial dysfunction, and the development of thrombotic and hemorrhagic complications. Several clinically relevant viruses, including SARS-CoV-2, influenza virus, HIV, dengue virus, and viral hemorrhagic fever-associated pathogens, have been shown to directly or indirectly interact with platelets through surface receptors, immune complexes, and inflammatory mediators, leading to platelet activation, phenotypic reprogramming, and accelerated clearance. These processes contribute to the paradoxical coexistence of thrombocytopenia and hypercoagulability that characterizes many severe viral diseases. Moreover, platelets can act as immune sentinels by sensing viral components, releasing cytokines and chemokines, forming platelet\u2013leukocyte aggregates, and modulating both innate and adaptive immune responses, thereby shaping the clinical course of infection. In this review, we synthesize current evidence on the molecular and cellular mechanisms governing virus\u2013platelet interactions, with particular emphasis on their role in immune-thrombosis, endothelial injury, and organ dysfunction. We further discuss the clinical implications of platelet dysregulation in viral infections, including its potential value as a biomarker of disease severity and as a therapeutic target. Understanding the platelet\u2013virus axis provides a unifying framework to explain the thrombo-inflammatory phenotype of viral diseases and may open new avenues for risk stratification and targeted interventions in affected patients.<\/jats:p>","DOI":"10.3390\/v18020183","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T10:08:57Z","timestamp":1769681337000},"page":"183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Platelet\u2013Virus Axis in Human Disease"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-1074","authenticated-orcid":false,"given":"Carmine","family":"Siniscalchi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital, 43100 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Basaglia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Parma University Hospital, 43100 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2656-5467","authenticated-orcid":false,"given":"Egidio","family":"Imbalzano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98121 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-4598","authenticated-orcid":false,"given":"Pierpaolo","family":"Di Micco","sequence":"additional","affiliation":[{"name":"Internal Medicine Ward, P.O. Pozzuoli, ASL Napoli2 Nord, 80078 Pozzuoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1182\/blood-2013-11-536003","article-title":"Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis","volume":"124","author":"Koupenova","year":"2014","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hottz, E.D., Bozza, F.A., and Bozza, P.T. (2018). Platelets in Immune Response to Virus and Immunopathology of Viral Infections. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00121"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Schrottmaier, W.C., Schmuckenschlager, A., Pirabe, A., and Assinger, A. (2022). Platelets in Viral Infections\u2014Brave Soldiers or Trojan Horses. Front. 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