Monocyte/Macrophage Infection Is Associated with the Development of Simian Immunodeficiency Virus Encephalitis in Pigtailed Macaques

Abstract

The brains of individuals with lentiviral-associated encephalitis contain an abundance of infected and activated macrophages. It is hypothesized that encephalitis develops when increased numbers of infected monocytes traffic into the CNS during end stages of immunosuppression. The relationship between development of encephalitis and circulation of infected monocytes and why only a fraction of infected hosts develop lentiviral encephalitis is unknown. We proposed to examine the whether monocyte/macrophages from pigtailed macaques that develop simian immunodeficiency virus (SIV) encephalitis (SIVE) contain more replication competent virus than macaques that do not develop SIVE during the course of infection and at necropsy. Compared to macaques that did not develop SIVE, the monocyte associated SIV-DNA load of monocytes and the capability of monocyte-derived macrophages and nonadherent PBMC to produce virus ex vivo was increased in macaques that developed SIVE. Macaques with SIVE had more infected macrophages in peripheral organs with the exception of lymph nodes. Brains with SIVE had greater numbers of T cells and NK cells with cytotoxic potential than brains without encephalitis. However, T cell and NK cell infiltration in SIVE was more modest than observed in classical acute viral encephalitides. These findings support the hypothesis that inherent differences in host monocyte/macrophage viral production are associated with the development of encephalitis.