Characterization of the Neuroinflammatory Response During Pseudorabies Virus Infection in Mice

Thesis Type:

Undergraduate Senior Thesis

Abstract:

When infected with the wild-type virus strain of pseudorabies virus (PRV-Becker), mice will exhibit symptoms including a “mad-itch” response, tremors, and weight loss, and eventually die. Interestingly, an attenuated version of PRV (PRV-Bartha) is significantly less virulent. PRV-Bartha elicits less severe symptoms in infected mice and these mice will, on average, live significantly longer. Past rtPCR analysis has shown that these viruses do not replicate beyond the PNS and CNS, yet peripheral organs express elevated levels of pro-inflammatory cytokines and chemokines at the time of PRV-Becker infected animal death. These results have suggested that it is the inflammatory response to PRV as opposed to viral replication in tissues that kills the mice. Currently, little is known about the exact causes of death and of pruritus in the mice when infected with PRV-Becker. It is also unknown why PRV-Bartha is so much less virulent than PRV-Becker. This report characterizes the virulence of the PRV-Becker strain in a murine model by comparing it to the attenuated, PRV-Bartha strain. rtPCR and ELISA analysis conducted in this study shows that PRV-Becker elevates G-CSF levels at early timepoints post infection and a systemic immune response consisting of both G-CSF and IL-6 across organs shortly follows this initial peak of G-CSF. Furthermore, we found that by effectively knocking out type-I IFN signaling in a mouse model, PRV-Bartha induces an immune response more similar to the PRVBecker strain. With IFN signaling absent, PRV-Bartha induces higher levels of G-CSF and viral load in the Dorsal Route Ganglion (DRG). These results promote a model of infection whereby, PRV-Becker is more virulent due to its ability to successfully evade the IFN response. Overall, this study furthers our understanding on the pathogenesis and virulence of PRV and provides potential molecular targets for future therapies.

http://arks.princeton.edu/ark:/88435/dsp01s4655k44z