In a groundbreaking study recently published in Science Bulletin, a collaboration between researchers at Peking University Health Science Center and Harbin Veterinary Research Institute unveiled an unprecedented mechanism of viral dissemination that challenges existing paradigms of viral spread. This study identifies a novel entity termed the “Migrion,” a chimeric structure arising from the intimate association between migrating host cells and vesicular stomatitis virus (VSV), which collectively redefines how viruses leverage cellular machinery for systemic infection.
Traditional models of intercellular viral transmission focus heavily on free virions—viral particles released extracellularly to infect adjacent or distant cells. However, this new research reveals that VSV hijacks a unique cellular organelle, the migrasome, which is specifically generated during the process of cell migration. Migrasomes are large extracellular vesicle-like structures formed on retraction fibers as cells actively move. The researchers demonstrate that VSV nucleic acids and proteins are actively sorted and incorporated into migrasomes in infected cells, thereby generating large, virus-containing structures they have metaphorically named “Migrions.” These Migrions differ significantly in both morphology and infection dynamics from traditional free virus particles.
A detailed mechanistic dissection highlights that Migrions carry multiple copies of viral genomes within a single vesicle, effectively packaging viral nucleic acids together with VSV glycoprotein G (VSV-G) on their surfaces. This organization allows Migrions to function as collective infectious units that utilize the host cell’s migratory pathways for effective intercellular spread. The collective transmission model inferred from this packaging implies a form of viral delivery that enhances replication efficiency by introducing a multiplicity of viral genomes simultaneously into recipient cells, a stark contrast to the one-particle-one-infection model prevailing in viral biology.
One of the critical aspects examined by the authors is the entry pathway of Migrions into recipient cells. Migrions penetrate target cells through receptor-independent endocytosis, bypassing the need for specific receptor recognition that typically mediates viral entry. Once internalized, the acidic environment of the endosome activates the fusogenic capacity of VSV-G, facilitating membrane fusion that releases the viral cargo into the cytoplasm. This step is essential for kick-starting viral replication, underscoring a sophisticated mechanism whereby Migrions exploit the host’s endosomal trafficking and pH dynamics for efficient cargo delivery.
From an infection kinetics perspective, the study reveals that Migrion-mediated transmission accelerates viral replication compared to infections initiated by free VSV particles. This phenomenon is attributed to the collective delivery mechanism, where multiple viral genome copies simultaneously enter the host cytoplasm, bypassing stochastic bottlenecks that usually limit infection success. The researchers further elucidate that this mechanism allows for enhanced viral fitness and rapid dissemination within host tissues, contributing substantially to viral pathogenicity.
A fascinating and unexpected finding of the study is the ability of Migrions to facilitate co-transmission of heterologous viruses. Unlike classical extracellular vesicles (EVs) that are often limited by specific host factors, Migrions appear capable of harboring and transmitting viral nucleic acids from other viruses concomitantly. This co-infection capability hints at a broader role for Migrions in viral ecology and provides new insights into how viral populations may exchange genetic material and pathogenic traits in vivo, potentially accelerating viral evolution and emergence.
In vivo studies conducted using murine infection models further substantiate the significance of Migrions in pathogenesis. Compared to infections initiated by free virions, Migrion-mediated infections resulted in markedly enhanced infectivity and exacerbated disease severity. The animals developed severe pulmonary and cerebral manifestations, including encephalitis, which ultimately culminated in lethal outcomes. These findings highlight that Migrions are not just an in vitro curiosity but represent a critical player in systemic viral infections with profound clinical implications.
Delving deeper into the biology of the Migrion, the researchers propose that this entity arises specifically through the coupling of viral components with migrasome biogenesis pathways inherent to migrating cells. Migrasomes, typically involved in cellular communication and debris clearance, are here repurposed as viral dissemination platforms. This breakthrough advances our understanding of host-virus interplay by revealing that viruses can exploit the cellular migration machinery to maximize their spread within a host organism, expanding the conceptual framework for viral ecology and host-pathogen interactions.
At the molecular level, the study highlights several intriguing observations. The selective incorporation of viral nucleic acids and VSV structural proteins into migrasomes suggests the presence of viral or host factors that mediate this sorting process. While specific molecular determinants remain to be elucidated, these preliminary findings open avenues for targeted antiviral interventions aimed at disrupting Migrion formation, thereby potentially limiting viral dissemination and pathogenicity.
Moreover, the receptor-independent uptake mechanism for Migrions broadens the scope of viral entry biology. By circumventing canonical receptor-mediated pathways, Migrions potentially neutralize some host defense mechanisms aimed at blocking receptor binding. This feature might explain the increased infective prowess of Migrions and could inspire future studies to explore how viruses might similarly exploit alternative entry routes in various host-pathogen systems.
The discovery of Migrions carries immense implications for virology, immunology, and therapeutic development. It challenges the dogma that extracellular free virus particles are the sole or primary vectors for intercellular viral spread. Instead, it underscores a sophisticated evolutionary adaptation wherein viruses co-opt fundamental cellular functions, such as migration and vesicle formation, to optimize their life cycle. Understanding and targeting this interaction could pave the way for innovative antiviral strategies that disrupt the migratory-dependent dissemination pathway.
In summary, this pioneering research delineates an uncharted viral dissemination strategy through Migrions—hybrid virus-migrasome structures that fuse viral infectivity with cellular migratory processes. By illuminating how VSV leverages migrasome biogenesis to enhance infectivity, facilitate viral co-transmission, and exacerbate pathogenic outcomes, the study expands the conceptual landscape of viral dissemination. These insights will undoubtedly inspire a reevaluation of viral spread mechanisms and invigorate research into host-derived organelles as viral transmission platforms.
As next steps, investigators are poised to delve deeper into the molecular mechanisms governing Migrion biogenesis, cargo sorting, and recipient cell entry. Unraveling these processes holds promise for identifying therapeutic targets that interrupt this novel viral transmission route. Furthermore, exploring whether other viruses similarly harness migrasomes could broaden the relevance of this discovery across virology.
This transformative study not only enriches our understanding of viral pathogenesis but also underscores the dynamic interplay between viruses and host cellular infrastructure. By exploiting migrasome-mediated pathways, VSV and potentially other viruses reveal ingenious survival strategies that secure their propagation and virulence, providing new frontiers for combating viral diseases.
Subject of Research: Viral dissemination mechanisms; vesicular stomatitis virus (VSV); migrasome-mediated viral transmission
Article Title: Migrion: A novel migrasome-mediated viral dissemination pathway enhancing VSV infectivity and pathogenesis
Web References: http://dx.doi.org/10.1016/j.scib.2025.08.039
Image Credits: ©Science China Press
Keywords: Migrion, migrasome, vesicular stomatitis virus, viral dissemination, intercellular transmission, viral pathogenesis, receptor-independent endocytosis, viral co-transmission, viral replication kinetics, host-virus interactions
