Atlastin 1 functions as a pro-viral factor during GCRV infection by interacting with viral NS80 and perturbing cellular redox homeostasis.

Grass carp reovirus (GCRV) causes severe hemorrhagic disease in farmed grass carp, yet how GCRV exploits host membrane remodeling machinery to support replication remains poorly defined. Here, we identified grass carp atlastin-1 (gcATL1), an endoplasmic reticulum (ER) membrane-fusion GTPase, as a pro-viral host factor for GCRV infection. Structural and phylogenetic analyses confirmed that gcATL1 harbors conserved domains typical of vertebrate ATL1 orthologs. Transcriptional profiling revealed broad tissue distribution of gcATL1 and significant transcriptional induction in brain upon GCRV challenge. gcATL1 localized to the ER. Functional assays showed that gcATL1 overexpression enhanced GCRV propagation, accompanied by elevated viral titers, increased viral protein abundance, and aggravated cytopathic effects. Furthermore, overexpression of gcATL1 promoted viral inclusion bodies (VIBs) biogenesis, accompanied by progressively increased ER-VIB colocalization in a GBP-domain-dependent manner. Mechanistically, gcATL1 interacted with viral NS80 via its conserved GBP domain to facilitate viral replication. Meanwhile, gcATL1 disrupted cellular redox homeostasis and exacerbated virus-elicited oxidative stress injury. Collectively, our results reveal that GCRV hijacks gcATL1 to promote infection through coordinating viral protein interaction and host stress responses, offering novel insights into the involvement of host GTPase in aquatic reovirus pathogenesis.