The contribution of myeloid cells to HIV neuropathogenesis

This chapter discusses the role of myeloid cells in HIV neuropathogenesis. HIV infection of the CNS occurs early after peripheral infection, in part due to the transmigration of infected intermediate CD14+CD16+ monocytes across the BBB into the CNS. Some of these infected monocytes can differentiate into long-lived macrophages upon entry into the CNS. Macrophages constitute an important CNS viral reservoir even with ART. HIV produced by these cells can infect other resident macrophages within the CNS as well as microglia. HIV-infected cells produce inflammatory mediators and viral proteins that activate other CNS cells. This infection/activation promotes the transmigration of additional uninfected and infected monocytes and T cells across the BBB. Inflammatory mediators and viral and host neurotoxic factors produced in response to chronic infection and cell activation cause neuronal injury and the development of HIV-NCI. Infection and dysregulation of functions of macrophages and microglia contribute significantly to HIV CNS disease.