Dissecting the Anterograde Spread Defect of HSV-1 Strain McIntyre in Neurons

Thesis Type:

Undergraduate Senior Thesis

Abstract:

Viruses are increasingly being used as tracers of neural connections in the nervous systems of animal models. The herpes simplex virus 1 (HSV-1) is a prime target for ongoing research, due to its broad host range, which includes rodents, higher primates and humans. Wild-type HSV-1 can spread in both directions (retrogradely and anterogradely) in a polysynaptic circuit. A strain of HSV-1 known as McIntyre exhibits a unique abrogation of anterograde spread in infected neurons and can only spread in a retrograde fashion. This thesis sought to determine the mechanisms behind this defect, with a specific focus on viral proteins gI and US9. The addition of wild-type gI and US9 proteins led to a significant but incomplete rescue of anterograde spread. Further work must be done to elucidate the effects of glycosylation, the mechanisms of motor recruitment, and the repair of other mutated genes on the spreading abilities of HSV-1 McIntyre. Given that HSV-1 is a chronic human pathogen with very high incidence, understanding its viral spread will be critical to improving antiviral treatments.

http://arks.princeton.edu/ark:/88435/dsp01dn39x4270