Extracellular vesicles (EVs), consisting of exosomes, micro-vesicles, and other vesicles, mainly originate from the multi-vesicular body (MVB) pathway or plasma membrane. EVs are increasingly recognized as a tool to mediate the intercellular communication and are closely related to human health. Viral infection is associated with various diseases, including respiratory diseases, neurological diseases, and cancers. Accumulating studies have shown that viruses could modulate their infection ability and pathogenicity through regulating the component and function of EVs. Non-coding RNA (ncRNA) molecules are often targets of viruses and also serve as the main functional cargo of virus-related EVs, which have an important role in the epigenetic regulation of target cells. In this review, we summarize the research progress of EVs under the regulation of viruses, highlighting the content alteration and function of virus-regulated EVs, emphasizing their isolation methods in the context of virus infection, and potential antiviral strategies based on their use. This review would promote the understanding of the viral pathogenesis and the development of antiviral research.

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When establishing persistent infection in most human hosts, EBV is usually latent. How the viral latency is maintained in cells remains largely unknown. c-Myc was recently reported to act as a controller of the lytic switch, while whether and how EBV regulates it remain to be explored.

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening syndrome, which is caused by EBV infection that is usually refractory to treatment and shows relapse. The development of new biomarkers for the early diagnosis and clinical treatment of EBV-HLH is urgently needed. Exosomes have been shown to mediate various biological processes and are ideal non-invasive biomarkers. Here, we present the differential plasma exosomal proteome of a patient with EBV-HLH before vs. during treatment and with that of his healthy twin brother. A tandem mass tag-labeled LC-MS technique was employed for proteomic detection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that differential proteomic profiles were related to virus infection, coagulopathy, nervous system dysfunction, imbalance of immune response, and abnormal liver function. The candidate biomarkers were first identified in the patient’s plasma exosomes at different treatment and follow-up time points. Then, 14 additional EBV-HLH exosome samples were used to verify six differentially expressed proteins. The upregulation of C-reactive protein, moesin, galectin three-binding protein, and heat shock cognate 71 kDa protein and the downregulation of plasminogen and fibronectin 1 could serve as potential biomarkers of EBV-HLH. This plasma exosomal proteomic analysis provides new insights into the diagnostic and therapeutic biomarkers of EBV-HLH.

Deubiquitylating enzymes (DUBs) are proteases that crack the ubiquitin code from ubiquitylated substrates to reverse the fate of substrate proteins. Recently, DUBs have been found to mediate various cellular biological functions, including antiviral innate immune response mediated by pattern-recognition receptors (PRRs) and NLR Family pyrin domain containing 3 (NLRP3) inflammasomes. So far, many DUBs have been identified to exert a distinct function in fine-tuning antiviral innate immunity and are utilized by viruses for immune evasion. Here, the recent advances in the regulation of antiviral responses by DUBs are reviewed. We also discussed the DUBs-mediated interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antiviral innate immunity. The understanding of the mechanisms on antiviral innate immunity regulated by DUBs may provide therapeutic opportunities for viral infection.

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