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HIV-1 Nef enhances dendritic cell (DC)-mediated viral transmission to CD4 +  T cells, but the underlying mechanism is not fully understood. It is also unknown whether HIV-1 infected DCs play a role in activating CD4 +  T cells and enhancing DC-mediated viral transmission. Here we investigated the role of HIV-1 Nef in DC-mediated viral transmission and HIV-1 infection of primary CD4 +  T cells using wild-type HIV-1 and Nef-mutated viruses. We show that HIV-1 Nef facilitated DC-mediated viral transmission to activated CD4 +  T cells. HIV-1 expressing wild-type Nef enhanced the activation and proliferation of primary resting CD4 +  T cells. However, when co-cultured with HIV-1-infected autologous DCs, there was no significant trend for infection- or Nef-dependent proliferation of resting CD4 +  T cells. Our results suggest an important role of Nef in DC-mediated transmission of HIV-1 to activated CD4 +  T cells and in the activation and proliferation of resting CD4 +  T cells, which likely contribute to viral pathogenesis.

HIV-1 Nef Enhances Dendritic Cell-Mediated Viral Transmission to CD4+ T Cells and Promotes T-Cell Activation