Axonal entry and retrograde transport define HSV-1 latency establishment and reactivation potential in neurons
Year: 2026
Type: preprint
Abstract: models bypass the physiological route of infection by directly infecting neuronal cell bodies under antiviral suppression. Here, we established a compartmented axonal infection model that recapitulates HSV-1 neuroinvasion and latency establishment without pharmacological inhibitors. Using primary superior cervical ganglion (SCG) neurons, we demonstrated that low-dose axonal infection consistently establishes latency, whereas higher axonal doses or direct somatic infection led to productive replication. Latently infected neurons exhibit accumulation of the latency-associated transcript (LAT) and can be efficiently reactivated by UV-inactivated virus or VP16 expression. Remarkably, productive infection can be induced during low-dose axonal infection by simultaneous exposure of neuronal cell bodies, but not axons, to replication-deficient virions, implicating tegument delivery in soma overrides latency establishment. Conversely, excess replication-incompetent particles in axons suppress productive outcomes and subsequent reactivations, suggesting competition for retrograde transport. Together, these findings identify axonal entry and transport as critical regulatory checkpoints in HSV-1 latency establishment and suggest that interference with retrograde trafficking may represent a strategy to limit neuroinvasion and life-long reactivations.
Institution: University of California, Irvine
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Establishing a Laboratory Model of Herpes simplex virus (HSV) Latency Using Compartmented Neuron Cultures, The Role of Interferon Lambda in Alpha Herpesvirus Neuroinvasion, The UC Irvine Center for Neural Circuit Mapping training program in Alzheimer's disease research, Neuroimmunology Training Program at the University of California, Irvine
OpenAlex ID: W7214277256