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The vesicular stomatitis virus life cycle is a multi-stage biological process characteristic of negative-stranded RNA viruses in the family Rhabdoviridae. The cycle begins with viral attachment to host cells through nonspecific electrostatic and hydrophobic interactions, followed by clathrin-mediated endocytosis in a dynamin-2-dependent manner requiring actin polymerization. The virus enters through early endosomes where a pH drop below 6.5 triggers G protein conformational changes enabling membrane fusion and nucleocapsid release into the cytoplasm within 2 minutes. The viral ribonucleoprotein core, comprising the viral genome encapsidated with N protein, serves as the template for transcription by the viral RNA-dependent RNA polymerase (L protein complex with P protein). This produces leader RNA and mRNAs encoding five viral proteins. Early replication steps occur within the first few hours, while later stages including viral assembly and budding take 12-18 hours to complete. Assembly involves condensation of the viral ribonucleoprotein core with matrix protein during budding from the plasma membrane. The matrix protein contains late domains that engage host ESCRT machinery to facilitate viral particle release. Host cell factors from multiple pathways including the secretory pathway (COPII and COPI complexes) and endocytic machinery are critically involved throughout the replication cycle.
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