| Herpetic
Eye Disease.
Viral Herpes Simplex Ocular Infection.
Herpes simplex virus type 1 (HSV) is the most common cause of infectious
blindness in the U.S., with approximately 500,000 cases of ocular
herpetic keratitis reported annually. 
The clinical
significance of herpetic viral infections, in particular infections
involving cytomegalovirus and HSV retinopathy in immunocompromised
patients, motivates us to study how herpes virus attaches to and
enters host neurons and pirates the host cell machinery, cytoplasmic
motors and cytoskeletal elements to travel back to the nucleus,
the intracellular target for viral production. Once in the nucleus,
the virus may begin to replicate and destroy that neuron or become
quiescent. In recurrent herpetic ocular infections, previously quiescent
virus reactivates and once again uses host cell machinery and motors
to travel in the opposite direction in axons to the cornea where
the resulting blisters may scar and compromise vision.
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Intraocular
Transport Model.
The
targeted intracellular transport of HSV is essential for transmission
of virus through the nervous system. However, molecular and cell
biological features of the bidirectional transport of the virus
have yet to be well-defined. Our goal is to provide basic cell
biology and molecular information about directed transport of
a viral particle.
We have adopted the strategy of using genetically different HSV
strains. We examine the cytological and biochemical characteristics
of the various mutant strains as they move within retinal ganglion
cell neurons. This allows us to compare the viral components that
are essential for transport and to tease out the host cell elements
that are also necessary.
We have begun to unravel the molecular signals involved in the
infection and transport of the herpes virus. In the future, we
hope to extend the investigation to other clinically significant
neurotropic viruses, such as cytomegalovirus, and varicella-zoster
virus. Our long-term goal to develop a therapeutic means of interrupting
the intracellular transport of these viruses and thus to block
new neuronal infection, as well as recurrent corneal and retinal
disease.
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