Role of gp120 in dendritic cell dysfunction in HIV infection

Only a limited fraction of circulating virions are demonstrably infectious; therefore, exposure to inactivated viruses may mimic the most frequent type of CD4-HIV interactions that occur in vivo. Several studies have recently underscored the crucial role that those noninfectious viruses could play in defective immune function in HIV-infected individuals and in particular, in the dysregulation of dendritic cell (DC) function. In this review, we discuss how interactions between DC and HIV gp120 or inactivated virus, which harbor intact surface gp120, lead to impaired DC function through direct (direct contact) or indirect mechanisms (as a consequence of primary CD4+ T cell dysregulation, followed by defective CD4-DC interactions). It is important that these functionally impaired DCs fail to give optimal signal to T cells but appear to favor the emergence of regulatory T cells. gp120-mediated impairment of DC function could therefore play an important role in the pathogenesis of HIV disease.