Progress on protein corona around viruses

<sec><p indent="0mm">Viruses entering a living organism navigate a complex journey through biological fluid environments, where interactions with host factors can affect viral infectivity, immunogenicity, and pathogenicity. Investigation of virus-biological fluid interactions is of great significance for deepening our understanding of virus-host interactions and for developing novel antiviral strategies. Conventionally, virological studies primarily elucidated the interactions between viral particles and individual host components in biological fluids along with the biological effects. In this review, we first briefly outline the interactions between viruses and typical proteins in the blood (e.g., immunoglobulins, complement proteins, coagulation factors), revealing intricate “inhibition-promotion” regulatory networks. The unraveling of these molecular mechanisms has offered crucial insights for developing effective immunotherapies and vaccines. However, viruses encounter numerous biomolecules simultaneously in biological fluids. Thus, it is essential to gain a deeper, more comprehensive understanding of these intricate interactions. </sec><sec> A protein corona is often referred to as a layer of proteins absorbed on a nanoparticle in a biological fluid. Protein coronas can redefine the surface properties of nanoparticles and influence their <italic>in</italic> <italic>vivo</italic> fate. Recent studies have suggested that viruses, as naturally occurring nanoparticles, also engage in competitive or cooperative interactions with multiple components within biological fluids, forming a dynamic, multi-component surface modification layer known as the viral protein corona. Similarly, the viral protein corona endows viruses with new surface properties, which subsequently influence their biological behaviors, including infectivity, immune response, and pathogenic mechanisms. On the other hand, viruses and virus-like particles, as an emerging class of bionanoplatforms, have demonstrated great promise in biomedical applications owing to their advantages of precise structure, excellent biocompatibility, and programmable functionalization. In this regard, the formation of viral protein coronas has been demonstrated to enable alteration of the biological effects of virus-based nanoparticles, such as targeting, immunogenicity, and biodistribution. The study of viral protein corona offers a novel perspective and research framework for understanding virus-biological fluid interactions, thereby opening new avenues for elucidating viral behavior and promoting applications of virus-based nanomaterials. </sec><sec> In this review, we have systematically summarized the advances of viral protein coronas from the aspects of their formation and dynamic evolution, methodologies for their study, and their compositions and corresponding biological effects. We conclude that: (i) the compositions of viral protein coronas correlate with complex factors, including viral type, biological fluid species, and surface physicochemical properties; (ii) the resultant biological effects of viral protein coronas are probably mediated by the collective of multiple adsorbed biomolecules rather than by a single constituent; (iii) functional modification of viral particles leads to the formation of specific protein corona profiles, and manipulation of viral protein coronas enables the regulation of viral biological effects. Protein corona studies enable systematic identification of important components in biological fluids that may influence viruses’ targeting ability, infectivity, immune responses, and <italic>in</italic> <italic>vivo</italic> fate. Therefore, viral protein coronas hold great promise for extending and deepening our understanding of virus-host interaction mechanisms, developing novel antiviral strategies, and designing virus-based functional nanomaterials. Lastly, several issues and challenges have been discussed, including the separation methodologies, standardized experimental and analysis workflows, in-depth studies on molecular mechanisms underlying the biological effects of viral protein coronas, and the application of artificial intelligence in protein corona research. </sec>