Neuropilin-1, a myeloid cell-specific protein
Macrophages and dendritic cells represent an important target for HIV-1 replication in vivo because they serve both as a vehicle for virus dissemination throughout the body and as a viral reservoir.
However, myeloid cells can support persistent HIV-1 replication and, unlike infected T cells, demonstrate lower productivity. Using proteomics, we discovered that NRP-1 is a host restriction factor that prevents HIV-1 from infecting macrophages and dendritic cells.
NRP-1 is incorporated into the HIV-1 virion particle to inhibit its ability to bind to target cells in a viral envelope glycoprotein-independent manner. Taken together, these results provide insight into the ability of myeloid lineage cells to use NRP-1 to interfere with HIV-1 infection.
Cells of the myeloid lineage such as macrophages and dendritic cells (DC), targeted by HIV-1, are important vehicles for the dissemination of the virus in the organism as well as viral reservoirs. Compared to activated lymphocytes, myeloid cells are collectively more resistant to HIV-1 infection.
Here we report that NRP-1, encoding the transmembrane protein neuropilin-1, is highly expressed in macrophages and DCs, but not in CD4+ T cells, serving as an anti-HIV factor to inhibit the infectivity of progeny virions of the HIV-1. Silencing NRP-1 significantly enhanced HIV-1 transmission in macrophages and DCs and increased the infectivity of virions produced by these cells.
We further demonstrated that NRP-1 was packaged into progeny virions to inhibit their ability to bind to target cells, thereby reducing virion infectivity. These data indicate that NRP-1 is a newly identified antiviral protein highly produced in both macrophages and DCs that inhibit HIV-1 infectivity; thus, NRP-1 may be a new therapeutic strategy for the treatment of HIV-1 infection.