Common causes of olfactory dysfunction include upper respiratory infections (URI) and the """"""""common cold"""""""". However, the anatomical basis and pathogenetic mechanisms underlying this post-viral olfactory dysfunction (PVOD) are not well understood. The overall aim of the proposed project is to use experimental animal models to analyze the ability of the olfactory system to function and recover when compromised by two distinct viral insults, which have their impact at different sites in the olfactory system after intranasal inoculation. One model employs an olfactory bulb-targeted infection in mice caused by an olfactory bulb line variant virus (PBLV), which is derived from the JHN strain of mouse hepatitis virus. The second employs an olfactory epithelium-targeted infection caused by sialodacryoadenitis virus (SDAV). OBLV and SDAV are both coronaviruses and are classified in antigenic group II, along with several human coronaviruses that are frequent causes of the common cold. The damage and recovery caused by each of these infections will be evaluated by virological, anatomical and functional approaches. The virological studies will use viral culture, immunohistochemical staining for viral antigen, and standard immunological assays to determine the specific cell types infected in the epithelium and bulb, the spread of the virus from the olfactory epithelium to the CNS, and the role of the inflammatory response in viral clearance and/or tissue damage. Anatomical evaluation will utilize conventional histological techniques, immunohistochemistry in conjunction with the virological studies, and transport labeling techniques to determine the extent of damage, the particular cells damaged, the direct vs. indirect (or reflected damage) to the epithelium and the time course and degree of recovery. Functional evaluation will employ psychophysical methods, i.e. the five odorant identification task, and the neurophysiological recording of odorant-induced spatial activity patterns in the bulb and epithelium to determine the consequences and recovery from the two types of viral lesions. The specific behavioral tasks will evaluate the recovery of performance on the odorant identification task to pre-infection levels, and the effect of viral insult on perceived odorant quality at long survivals or at the time of behaviral recovery. The results of these studies will provide insights into the anatomical and function consequences of viral insults on olfaction and will have reference to human PVOD. These studies will allow us to determine the extent of viral-induced peripheral or central olfactory damage that is necessary to cause dysomia. In addition, we will determine the extent, degree and location of viral damage from which behavioral recovery is possible. A better understanding of these experimental models is likely to provide insight into the prognosis of post-viral olfactory loss and future therapeutic strategies.
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