Host factor Naf1 restricts HIV-1 infection of myeloid cells and compromises the capacity of dendritic cell to prime CD4+ T cell.

Abstract

Naf1 (Nef-associated factor 1) is a host protein that interacts with human immunodeficiency virus type 1 (HIV-1) Nef protein. We and others have previously demonstrated that Naf1 restricts HIV-1 infection of T-lymphocytes. Myeloid cells are targets for HIV infection, but Naf1 expression in myeloid cells and whether it also regulates HIV infection in these cells are not yet identified. In this study, we found that Naf1 had a higher expression in CD14⁺ monocytes than in monocyte-derived dendritic cells (MDDCs), and its expression in both types of cells could be induced by HIV-1 gp120 glycoproteins or viral particles. Importantly, the expression of Naf1 restricted HIV-1 infection in monocytes and MDDCs. Functional investigation showed that both the constitutive and the induced expression of Naf1 inhibited NF-κB signaling in MDDCs and reduced the basal level or LPS (Lipopolysaccharide)-stimulated production of cytokines. Moreover, Naf1 reduced the expression of ICAM-1 (intercellular cell adhesion molecule-1) on MDDCs and compromised their capacity to prime the activation of resting CD4⁺ T cells in co-culture. In light of the essential role of NF-κB signaling for HIV-1 transcription, Naf1-mediated inhibition of NF-κB signaling may hinder a robust viral replication in MDDCs and help maintain viral persistence. Furthermore, virus-induced Naf1 expression in MDDCs may diminish the cross-talk between DC (dendritic cell) and T cells, hence suppressing the activation of antiviral immune responses. Taken together, we identified the new function of Naf1 in myeloid cells. Those findings may facilitate the understanding for the host restriction of HIV-1 infection in myeloid cells.