Dynamin-Independent Endocytosis in Viral Entry: Mechanistic Diversity and Condition-Dependent Pathway Selection
Year: 2026
Type: article
Abstract: Viral entry into host cells is a fundamental determinant of infection efficiency, host range, tissue tropism, and pathogenicity, yet the mechanistic diversity of this process remains incompletely understood. Clathrinmediated endocytosis (CME) coupled with dynamin-dependent membrane scission has long served as the canonical model; however, accumulating evidence reveals that many viruses̶spanning large enveloped viruses (Ebola virus, vaccinia virus), medium-sized enveloped viruses (chikungunya virus, SARS-CoV-2, dengue virus), non-enveloped RNA viruses (echovirus, reovirus), and DNA viruses (adenovirus, SV40, human papillomavirus)̶exploit routes partially or entirely independent of dynamin. A central thesis of this review is that dynamin involvement in viral entry is not a binary property but a variable parameter along a mechanistic continuum, modulated by virus particle geometry, receptor expression, membrane composition, cytoskeletal state, and cell type. This perspective reframes apparently conflicting reports̶wherein dynamin inhibition partially rather than completely suppresses infectivity, or where the same virus uses distinct entry routes in different cellular contexts̶as reflections of condition-dependent pathway selection rather than categorically distinct mechanisms. This review further examines methodological limitations of pharmacological and genetic approaches and surveys the molecular diversity of co-existing dynamin-independent pathways, including macropinocytosis, the CLIC/GEEC route, the Arf6-regulated pathway, and fast endophilin-mediated endocytosis. Conceptualizing viral entry as a plastic process governed by the relative engagement of multiple endocytic pathways deepens our understanding of virus‒host interactions and suggests that targeting convergent downstream steps, rather than single entry routes, may yield more effective antiviral strategies.
Author: Sato, Hirotaka
Institution: Dokkyo Medical University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7222856380