Human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), the etiologic agent in the acquired immunodeficiency syndrome (AIDS), and cytomegalovirus, which frequently causes life-threatening organ pathology in AIDS patients, induce impaired T cell function in vivo. However, whether macrophage dysfunction contributes to this immunosuppression is unknown. Therefore, the goal of this project has been to determine whether these viruses are capable of infecting monocytes and whether infected monocytes exhibit impaired effector and/or antigen-presenting function. The results obtained thus far indicate that both HTLV-III/LAV and CMV can infect human monocytes. In addition, virus-infected monocytes appear to have impaired cell functions including chemotaxis, interleukin-1 production, cytotoxicity and accessory cell activity. In addition, preliminary results indicate that HTLV-III/LAV (in vivo) and CMV (in vitro) induce maximal but suboptimal monocyte activation as determined by surface antigen expression and oxygen reactive intermediate generation. These findings strongly implicate virally induced impairment of monocyte function as contributing to the immunosuppression caused by HTLV-III/LAV and CMV.
