Human immunodeficiency virus (HIV) and cytomegalovirus (CMV) can induce severe lymphocyte suppression. Whether these viruses also cause monocyte dysfunction, which could contribute the lymphocyte immunosuppression, is unclear. Therefore, the goal of this project has been to determine whether HIV and CMV infect human monocytes and whether infected monocytes exhibit impaired cell functions. Early results indicate that HIV and CMV can infect monocytes. Monocytes infected with HIV in vivo exhibit impaired chemotaxis, interleukin-1 production, cytotoxicity, accessory cell activity and surface antigen/receptor expression. These findings are currently being confirmed in monocytes infected in vitro by macrophage-adapted strains of HIV. Results also indicate that monocytes infected with CMV exhibit reduced accessory cell functions but increased surface HLA-DR and IL-2 receptors and spontaneously secrete increased amounts of oxygen reactive intermediates. An investigation of the role of C. albicans, a pathogen of the oral cavity and esophagus in AIDS patients, has been initiated. Particular attention is being directed to monocyte cytotoxicity of Candida, to identification of the subgroup of Candida infecting AIDS patients, and to the role of Candida cell wall mannon in the pathogenicity of the C. albicans isolated from AIDS patients. In clinical investigations, the etiology and therapy of the enteric infections in AIDS is being evaluated. In the majority of symptomatic patients, identifiable enteric pathogens, particularly CMV, have been identified. Contributing to the high frequency of enteric infections in AIDS patients may be their impaired ability to develop de novo antibody responses to enteric microorganisms such as G. lamblia which we have recently documented. The mechanism of the impaired B cell response in AIDS patients will be addressed in vitro by investigating the role of HIV infection of monocytes in altering the regulation of the B cell production of IgM and IgG. Also, investigation of the malabsorption association with AIDS indicates that HIV itself may be capable of inducing malabsorption.
