VIRAL PERSISTENCE IN NEURONS ALTERS SYNAPTIC PLASTICITY AND COGNITIVEFUNCTIONS WITHOUT DESTRUCTION OF BRAIN-CELLS

Neurons have a restricted expression of MHC heavy chain molecules whic h prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establis hment of noncytolytic persistent infection. Here we show that a chroni c noncytolytic viral infection both in vitro and in vivo selectively p erturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GA P-43 expression was greatly decreased in the hippocampus, an area of h eightened viral replication, while synaptic density was preserved. Con currently, the ability to learn tasks was significantly impaired in th ese persistently infected mice. Yet, infected neurons remained free fr om structural injury. (C) 1996 Academic Press, Inc.