A TRANSGENIC MOUSE MODEL FOR MEASLES-VIRUS INFECTION OF THE BRAIN

In addition to the rash, fever, and upper respiratory tract congestion that are the hallmarks of acute measles virus (MV) infection, invasio n of the central nervous system (CNS) can occur, establishing a persis tent infection primarily in neurons, The recent identification of the human membrane glycoprotein, CD46, as the MV receptor allowed for the establishment of transgenic mice in which the CD46 gene was transcript ionally regulated by a neuron-specific promoter, Expression of the mea sles receptor rendered primary CD46-positive neurons permissive to inf ection with MV-Edmonston, Notably, viral transmission within these cul tures occurred in the absence of extracellular virus, presumably via n euronal processes, No infection was seen in nontransgenic mice inocula ted intracerebrally with MV-Edmonston, In contrast, scattered neurons were infected following inoculation of transgenic adults, and an impre ssive widespread neuronal infection was established in transgenic neon ates, The neonatal infection resulted in severe CNS disease by 3-4 wee ks after infection, Illness was characterized initially by awkward gai t and a lack of mobility, and in later stages seizures leading to deat h, These results show that expression of the MV receptor on specific m urine cells (neurons) in vivo is absolutely essential to confer both s usceptibility to infection and neurologic disease by this human virus, The disparity in clinical findings between neonatal and adult transge nic mice indicates that differences exist between the developing and m ature CNS with respect to IMV infection and pathogenesis.