image: Flaviviruses disseminated in mosquito haemolymph by hijacking extracellular vesicles to overcome the acidic environment. Amino acids 723 and 728 of mosquito VCP determine the vector specificity of mosquitoes for flaviviruses. In vivo ectopic expression of CqVCP(E723D/E728N) rendered Cx quinquefasciatus susceptible to DENV2 infection. EVs: Extracellular vesicles; DENV: Dengue virus; ZIKV: Zika virus; JEV: Japanese encephalitis virus; CqVCP: Culex quinquefasciatus VCP.
Credit: Infectious Diseases & Immunity
Recently, an important commentary has been published in Infectious Diseases & Immunity, providing a clear answer to a core mystery that has plagued arbovirology for a century—why only a small subset of mosquito species can transmit specific flaviviruses.
Building upon a study reported in Nature (DOI: 10.1038/s41586-026-10100-x), the commentary highlights that transmission specificity does not stem from differences in intracellular viral replication but from molecular constraints governing systemic viral dissemination within mosquitoes. A key highlight is the discovery that flaviviruses traverse the acidic hemolymph via extracellular vesicles (EVs) rather than free virions, and the specific binding between mosquito valosin-containing protein (VCP) and viral capsid proteins acts as a critical "molecular gate" determining whether viruses can access this pathway. Notably, just two amino acid residues can rewrite transmission specificity.
This study not only establishes a unified molecular mechanism framework but also provides precise targets for flavivirus prevention and control, holding great promise for developing more efficient and environmentally friendly intervention strategies with significant basic research and public health value.
Journal
Infectious Diseases & Immunity
Method of Research
Commentary/editorial
Subject of Research
Not applicable
Article Title
Viral capsid–VCP interactions govern flavivirus vector specificity
Article Publication Date
20-Mar-2026
COI Statement
None