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Title: Pseudorabies Virus Replication and Spread in the Mouse Footpad Inoculation Model
Authors: Albrecht, Kristen
Advisors: Enquist, Lynn W
Department: Molecular Biology
Certificate Program: Global Health and Health Policy Program
Class Year: 2018
Abstract: Infection by alphaherpesviruses such as varicella-zoster virus (VZV) is a significant cause of neuropathic itch. VZV produces varicella or chickenpox upon primary infection, remains in a latent state in ganglia, and produces herpes zoster (HZ) or shingles if reactivated. Neuron damage from productive infection may lead to lasting pain or itch. In spite of various treatments and several vaccines, postherpetic itch continues to affect HZ patients. PHI is less studied than postherpetic neuralgia, and its mechanisms have not been defined. Pseudorabies virus (PRV), a swine alphaherpesvirus closely related to VZV, produces similar intense itching in non-natural hosts such as mice. Attenuated PRV-Bartha does not induce itch, so comparing PRV-Bartha and wildtype PRV-Becker will reveal the mechanisms of virus-induced neuropathic itch. To establish the mouse hind footpad inoculation model, we must first track how infection spreads and then identify inflammatory mediators responsible for pathology. This study focuses on the first objective; we aim to characterize viral spread and replication throughout the course of PRV-Becker infection. First, we detected PRV antigen in foot, bladder, kidney, and heart with immunohistochemistry at 72 hours post-inoculation (hpi). Using q-PCR to verify these results, we found PRV DNA in foot, dorsal root ganglia (DRG), spinal cord, and brain for both PRV-Becker (82 hpi) and PRV-Bartha (240 hpi). Finally, q-PCR at 24 and 48 hpi showed PRV-Becker replicates in the foot by 24 hpi. Infection spreads to the DRG and spinal cord between 48 and 82 hpi, correlating with development of itch around 66 hpi. Comparing these results with those from PRV-Bartha infection (ongoing experiments) and correlating with cytokine production will increase understanding of virus-induced neuropathic itch.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Molecular Biology, 1954-2022
Global Health and Health Policy Program, 2017-2022

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