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标题：Neuropilin-1, a myeloid cell-specific protein, is an inhibitor of HIV-1 infectivity
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作者：Shumei Wang ; Li Zhao ; Xiaowei Zhang 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：2
DOI：10.1073/pnas.2114884119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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. 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.
关键词：enHIV-1myeloid cellsNRP-1macrophagedendritic cell