Schwob J E, Saha S, Youngentob S L, Jubelt B
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
Chem Senses. 2001 Oct;26(8):937-52. doi: 10.1093/chemse/26.8.937.
Viral upper respiratory infections are the most common cause of clinical olfactory dysfunction, but the pathogenesis of dysosmia after viral infection is poorly understood. Biopsies of the olfactory mucosa in patients that complain of dysosmia after viral infection fall into two categories: one in which no olfactory epithelium is seen and another in which the epithelium is disordered and populated mainly by immature neurons. We have used intranasal inoculation with an olfactory bulb line variant of MHV to study the consequences of viral infection on peripheral olfactory structures. MHV OBLV has little direct effect on the olfactory epithelium, but causes extensive spongiotic degeneration and destruction of mitral cells and interneurons in the olfactory bulb such that the axonal projection from the bulb via the lateral olfactory tract is markedly reduced. Moreover, surviving mitral cells apparently remain disconnected from the sensory neuron input to the glomerular layer, judging from retrograde labeling studies using Dil. The damage to the bulb indirectly causes a persistent, long-term increase in the turnover of sensory neurons in the epithelium, i.e. the relative proportion of immature to mature sensory neurons and the rate of basal cell proliferation both increase. The changes that develop after inoculation with MHV OBLV closely resemble the disordering of the olfactory epithelium in some patient biopsies. 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 studying the pathogenesis of this form of dysosmia.
病毒性上呼吸道感染是临床嗅觉功能障碍最常见的原因，但病毒感染后嗅觉障碍的发病机制尚不清楚。对病毒感染后出现嗅觉障碍的患者进行嗅黏膜活检可分为两类：一类未见嗅上皮，另一类上皮紊乱，主要由未成熟神经元组成。我们通过鼻内接种小鼠肝炎病毒（MHV）的嗅球系变体来研究病毒感染对周围嗅觉结构的影响。MHV嗅球系变体对嗅上皮几乎没有直接影响，但会导致嗅球中大量的海绵状变性以及二尖瓣细胞和中间神经元的破坏，从而使嗅球经外侧嗅束的轴突投射明显减少。此外，从使用Dil的逆行标记研究判断，存活的二尖瓣细胞显然仍与嗅小球层的感觉神经元输入断开连接。嗅球的损伤间接导致上皮中感觉神经元更替持续长期增加，即未成熟与成熟感觉神经元的相对比例以及基底细胞增殖速率均增加。接种MHV嗅球系变体后出现的变化与一些患者活检中嗅上皮的紊乱非常相似。因此，嗅神经或嗅球的损伤可能导致一种病毒性后嗅觉功能障碍，而MHV嗅球系变体是研究这种嗅觉障碍发病机制的有用模型。
