Neuropilin-1, a myeloid cell-specific protein, is an inhibitor of HIV-1 infectivity

Significance Macrophages and dendritic cells represent an important target for HIV-1 replication in vivo as they serve both as a vehicle for virus dissemination throughout the body and a viral reservoir. However, myeloid cells can support persistent replication of HIV-1 and, in contrast to infected T cells, demonstrate lower productivity. Using proteomics, we discovered that NRP-1 is a host restriction factor that inhibits HIV-1 from infecting macrophages and dendritic cells. NRP-1 is incorporated into the HIV-1 virion particle to inhibit its ability to attach to target cells in a viral envelope glycoprotein-independent manner. Overall, these results provide insights into the ability of myeloid lineage cells to utilize NRP-1 to interfere with HIV-1 infection.