Intranasal inoculation with the olfactory bulb line variant of mouse hepatitis virus causes extensive destruction of the olfactory bulb and accelerated turnover of neurons in the olfactory epithelium of mice

Viral upper respiratory infections are the most common cause of clinical ol factory dysfunction, but the pathogenesis of dysosmia after viral infection is poorly understood. Biopsies of the olfactory mucosa in patients that co mplain of dysosmia after viral infection fall into two categories: one in w hich no olfactory epithelium is seen and another in which the epithelium is disordered and populated mainly by immature neurons. We have used intranas al inoculation with an olfactory bulb line variant of MHV to study the cons equences of viral infection on peripheral olfactory structures. MHV OBLV ha s little direct effect or the olfactory epithelium, but causes extensive sp ongiotic degeneration and destruction of mitral cells and interneurons in t he olfactory bulb such that the axonal projection from the bulb via the lat eral olfactory tract is markedly reduced, Moreover surviving mitral cells a pparently remain disconnected from the sensory neuron input to the glomerul ar layer, judging from retrograde labeling studies using Dil. The damage to the bulb indirectly causes a persistent, long-term increase in the turnove r of sensory neurons in the epithelium, i.e. the relative proportion of imm ature to mature sensory neurons and the rate of basal cell proliferation bo th increase. The changes that develop after inoculation with MHV OBLV close ly resemble the disordering of the olfactory epithelium in some patient bio psies. Thus, damage to the olfactory nerve or bulb may contribute to a form of post-viral olfactory dysfunction and MHV OBLV is a useful model for stu dying the pathogenesis of this form of dysosmia.