Alpha-herpesviruses infect a wide variety of cell types, but their hallmark is infection of the nervous systems of their hosts. Infections result in a variety of symptoms, some of which suggest an effect on motor and sensory neuron activity. For example, herpes simplex virus type 1 causes herpes labialis with the sensations of numbness and tingling ; herpes simplex virus type 2 causes genital herpes with the sensations of itching and pain ; and varicella-zoster virus causes chicken pox and shingles with sensations of itching, as well as intense pain . The focus of this thesis is toward understanding how herpesvirus infection affects the function and connectivity of peripheral nervous system (PNS) neurons. This understanding is central to understanding the cause of characteristic symptoms and pathogenesis.
We show that PRV infection of sympathetic neurons in vitro induces significant changes in electrical activity, as well as connectivity. Specifically, infection leads to increased action potential (AP) firing rates, preceded by the appearance of spikelets indicative of direct electrical connectivity between neurons. Further, as infection proceeds neurons become electrically continuous forming syncytia late in infection. The membrane fusion protein glycoprotein B (gB) is required for the observed changes in activity and connectivity. These changes suggest that similar changes could occur in vivo and may lead of symptoms of neurological dysfunction in infected animals.
|Advisor:||Enquist, Lynn W., Tank, David W.|
|School Location:||United States -- New Jersey|
|Source:||DAI-B 72/10, Dissertation Abstracts International|
|Subjects:||Molecular biology, Neurosciences, Cellular biology|
|Keywords:||Connectivity, Neuronal activity, Pseudorabies, Virus infection, Whole-cell patch clamp|
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