EXPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN THE NERVOUS-SYSTEM OF TRANSGENIC MICE LEADS TO NEUROLOGICAL DISEASE

Patients infected with the human immunodeficiency virus type 1 (HIV-1) frequently develop central and peripheral nervous system complication s, some of which may reflect the effect of the virus itself. In order to elucidate the pathogenic mechanisms of HIV in neurological disease in a small animal model, we generated transgenic mice expressing the e ntire HIV genome under control of the promoter for the human neurofila ment NF-L gene. The transgene was predominantly expressed in anterior thalamic and spinal motor neurons. Animals developed a neurological sy ndrome characterized by hypoactivity and weakness and by axonal degene ration in peripheral nerves. These results provide evidence for a role of HIV in affecting both the central and peripheral nervous systems, This animal model may also facilitate the development of therapeutic a gents against the human disease.