Expression of human immunodeficiency virus type 1 in the nervous system of transgenic mice leads to neurological disease

Abstract

Patients infected with the human immunodeficiency virus type 1 (HIV-1) frequently develop central and peripheral nervous system complications, 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 entire HIV genome under control of the promoter for the human neurofilament NF-L gene. The transgene was predominantly expressed in anterior thalamic and spinal motor neurons. Animals developed a neurological syndrome characterized by hypoactivity and weakness and by axonal degeneration 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 agents against the human disease.