The availability of a retrovirus-mouse model which in whole or in part mimics the etiology of AIDS and AIDS related diseases induced by human retroviruses will be very useful because of the pressing need to understand how these virus infections impair the host's immune and nervous systems. We therefore propose to use a murine retrovirus, MOMULV-tsl, which causes both severe immune and nervous system dysfunctions to study the pathogenesis of a spectrum of disorders that has many features in common with human retrovirus-induced diseases. We will attempt to I) Determine the nature of the immuno-suppressive properties of ts1 by investigating the effect of ts1 infection on T and B lymphocytes. II) Determine the role of the thymus in the ts1-induced pathogenesis by using nude and thymectomized mice as well as anti-thy-1 antibody to abolish T cells in BALB/c mice to determine whether intact T cells are required. III) Determine the role of macrophages in the ts1 -induced diseases by impairment of macrophages with silica treatment. IV) Determine the histopathological lesion in the pathogenesis of the ts1- induced diseases by studying the mechanism(s) by which the virus spread from the site of infection to the lymphoid and nervous systems and the mechanism(s) of lesion development in the lymphoid organs and the CNS. V) Identify the genetic determinant(s) which confer the immunosuppressive properties on ts1 by recombinant constructs between ts1 and MOMULV-TB. The studies proposed should result in a well defined MuLV-mouse model for further investigation of the molecular mechanism(s) of retrovirus induced immuno-deficiency and neuropathy. Furthermore, these studies may also enhance our understanding of the complex bidirectional interaction between the immune and nervous systems.
