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

Abstract

Myeloid lineage cells such as macrophages and dendritic cells (DCs), targeted by HIV-1, are important vehicles for virus dissemination through the body 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 transmembrane protein neuropilin-1, is highly expressed in macrophages and DCs but not CD4+ T cells, serving as an anti-HIV factor to inhibit the infectivity of HIV-1 progeny virions. Silencing NRP-1 enhanced the transmission of HIV-1 in macrophages and DCs significantly and increased the infectivity of the virions produced by these cells. We further demonstrated that NRP-1 was packaged into the progeny virions to inhibit their ability to attach to target cells, thus reducing the infectivity of the virions. 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 novel therapeutic strategy for the treatment of HIV-1 infection.

Toward the unveiling of HIV-1 dynamics: Involvement of monocytes/macrophages in HIV-1 infection

“…To date, it is clear that Env glycoprotein has a crucial role in the function of SERINC3/5, but its precise mechanisms of action remain incompletely understood (33)(34)(35)(36). Neuropilin-1 (NRP-1), a transmembrane protein, was newly identified in 2021 by Wang et al, and shown to inhibit progeny virus infection (Figure 2C) (37). This protein is highly expressed on the cell surface of macrophages and DCs but not on stimulated or resting CD4+ T cells.…”

Neuropilin-1 in the pathogenesis of preeclampsia, HIV-1, and SARS-CoV-2 infection: A review

“…This downregulates angiogenesis in vitro at concentrations similar to those which inhibit VEGF receptor binding ( Jia et al, 2001 ). A recent novel study identified NRP-1 as an antiviral protein for the treatment of HIV-1 infection ( Wang et al, 2022 ). Wang et al, observed resistance to HIV-1 infection in myeloid cells [macrophages and dendritic cells (DCs)] due to their high expression of transmembrane NRP-1 compared to CD4+ T cells ( Wang et al, 2022 ).…”

“…A recent novel study identified NRP-1 as an antiviral protein for the treatment of HIV-1 infection ( Wang et al, 2022 ). Wang et al, observed resistance to HIV-1 infection in myeloid cells [macrophages and dendritic cells (DCs)] due to their high expression of transmembrane NRP-1 compared to CD4+ T cells ( Wang et al, 2022 ). Furthermore, this study demonstrated that NRP-1 silencing facilitated the transmission of HIV-1 in macrophages and DCs significantly and amplified virion infectivity in these cells ( Wang et al, 2022 ).…”

“…Wang et al, observed resistance to HIV-1 infection in myeloid cells [macrophages and dendritic cells (DCs)] due to their high expression of transmembrane NRP-1 compared to CD4+ T cells ( Wang et al, 2022 ). Furthermore, this study demonstrated that NRP-1 silencing facilitated the transmission of HIV-1 in macrophages and DCs significantly and amplified virion infectivity in these cells ( Wang et al, 2022 ). However, the lack of literature on NRP-1 in HIV-1 infection prompts future research examining its regulation in viral infection.…”

Novel Nanotechnology-Based Approaches for Targeting HIV Reservoirs

“…The complete elimination of the virus from the body is not possible with current therapies due to the latency of the virus. Latent HIV-infected cells are often located in the secondary lymphoid tissue, testes, liver, kidney, lungs, gut, and central nervous system (CNS) [ 60 , 61 , 62 , 63 , 64 , 65 ]. The elimination of the virus from such reservoirs is crucial for a successful long-term treatment.…”