Molecular mechanisms of Batai virus entry into mouse neuroblastoma N2a cells via Clathrin-Mediated Endocytosis.

Batai virus (BATV), an arbovirus belonging to the family Peribunyaviridae, has garnered increasing attention due to its broad host range, expanding geographical distribution, and capacity to naturally infect the mammalian central nervous system with the potential for evolution into more virulent strains. As an enveloped virus, BATV enters host cells via endocytosis, with clathrin-mediated endocytosis (CME) representing the most extensively characterized entry mechanism. This study systematically investigated the molecular mechanisms underlying BATV entry into mouse neuroblastoma N2a cells via CME using pharmacological inhibitors, dominant-negative mutants, and siRNA interference approaches. Our findings demonstrate that BATV utilizes the CME pathway for cellular entry, relying on both early and late endosomes to facilitate internalization and release of the viral genome. The virus entry process requires the functional cooperation of clathrin, dynamin, and Eps15, followed by trafficking through Rab5-positive early endosomes and Rab7/Rab9-positive late endosomes in an acidification-dependent manner. This comprehensive understanding of BATV entry mechanisms provides a theoretical foundation for developing targeted antiviral strategies and therapeutic interventions against BATV-associated neurological diseases.