Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110122, China.
National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110122, China.
Proc Natl Acad Sci U S A. 2022 Jan 11;119(2). doi: 10.1073/pnas.2114884119.
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 , 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 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.
髓系细胞，如巨噬细胞和树突状细胞（DC），是 HIV-1 的靶向细胞，是病毒在体内传播和病毒储存的重要载体。与激活的淋巴细胞相比，髓系细胞总体上对 HIV-1 感染具有更强的抵抗力。在这里，我们报告 ，编码跨膜蛋白神经纤毛蛋白-1（NRP-1），在巨噬细胞和 DC 中高度表达，但在 CD4 T 细胞中不表达，作为一种抗 HIV 因子抑制 HIV-1 子代病毒颗粒的感染性。沉默 可显著增强 HIV-1 在巨噬细胞和 DC 中的传播，并增加这些细胞产生的病毒颗粒的感染性。我们进一步证明 NRP-1 被包装到子代病毒颗粒中，以抑制它们与靶细胞结合的能力，从而降低病毒颗粒的感染性。这些数据表明，NRP-1 是一种新鉴定的抗病毒蛋白，在巨噬细胞和 DC 中大量产生，抑制 HIV-1 的感染性；因此，NRP-1 可能是治疗 HIV-1 感染的一种新的治疗策略。
