Figure 7.

Proposed model for mechanisms underlying dysruption of the GA during HSV-1 neuronal infection. Alteration of the normal neuronal GA morphology by HSV-1 involves the activation of Src kinase signaling induced by the interaction of HSV-1 with cellular receptor(s). The prolonged activation of Src kinase activity during HSV-1 early infection triggers phosphorylation of Dyn2 (Tyr231), enhancement of Dyn2 assembly and GTPase activity at the GA. High Dyn2 activity induces membrane vesiculation, affecting GA morphology and function. In addition, assembly of HSV-1 virions ends with the acquisition of the viral envelope at the cis-Golgi, followed by their release from vesicles that emerge from the trans-Golgi network. We propose that activation of Src kinase and Dyn2 at the GA perturbs Golgi integrity affecting the secretory pathway in neurons. Consequently, alteration of the normal secretory pathway could impair and compromise neuronal function, and thereby contribute to neurodegenerative disorders development. L, ligands; R, cellular receptor; PM, plasma membrane; AF, actin filament; Src, Src kinase; P, phosphorylated; Dyn2, Dynamin 2 protein; G, Golgi; ER, endoplasmic reticulum; N, nucleus.