Classical antiviral restriction factors promote cellular immunity by their ability to interfere with virus replication and induction of their expression by proinflammatory cytokines such as interferons. The serine incorporator proteins SERINC3 and SERINC5 potently reduce the infectivity of HIV-1 particles when overexpressed, and RNA interference or knockout approaches in T cells have indicated antiviral activity also of the endogenous proteins. Due to lack of reagents for detection of endogenous SERINC proteins, it is still unclear whether SERINC3/5 are expressed to functionally relevant levels in different primary target cells of HIV infection and how the expression levels of these innate immunity factors are regulated. In the current study, analysis of SERINC3/5 mRNA steady-state levels in primary lymphoid and monocyte-derived cells revealed selective induction of their expression upon differentiation of myeloid cells. Contrary to classical antiviral restriction factors, various antiviral α-interferon subtypes and proinflammatory interleukins had no effect on SERINC levels, which were also not dysregulated in CD4+ T cells and monocytes isolated from patients with chronic HIV-1 infection. Notably, HIV-1 particles produced by terminally differentiated monocyte-derived macrophages with high SERINC5 expression, but not by low-expressing monocytes, showed a Nef-dependent infectivity defect. Overall, these findings suggest endogenous expression of SERINC5 to antivirally active levels in macrophages. Our results classify SERINC5 as an unconventional HIV-1 restriction factor whose expression is specifically induced upon differentiation of cells towards the myeloid lineage.
J Innate Immun

中文翻译：

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SERINC5是非常规的HIV限制因子，在髓样细胞分化过程中被上调。

经典的抗病毒限制因子通过其干扰病毒复制和通过促炎细胞因子（例如干扰素）诱导其表达的能力来促进细胞免疫。当过表达时，丝氨酸掺入蛋白SERINC3和SERINC5可以有效降低HIV-1颗粒的感染性，T细胞中的RNA干扰或敲除方法也表明内源蛋白也具有抗病毒活性。由于缺乏检测内源性SERINC蛋白的试剂，目前尚不清楚SERINC3 / 5是否在HIV感染的不同主要靶细胞中表达至功能相关的水平，以及如何调节这些先天免疫因子的表达水平。在本研究中，对SERINC3 / 5的分析原发性淋巴和单核细胞来源的细胞中的mRNA稳态水平揭示了骨髓细胞分化后选择性诱导其表达。与经典抗病毒限制因子相反，各种抗病毒α-干扰素亚型和促炎性白介素对SERINC水平无影响，在从慢性HIV-1感染患者中分离的CD4 + T细胞和单核细胞中也没有失调。值得注意的是，具有高SERINC5的终末分化单核细胞衍生巨噬细胞产生HIV-1颗粒表达，但不是由低表达的单核细胞表达，显示了Nef依赖的感染性缺陷。总体而言，这些发现表明SERINC5的内源性表达在巨噬细胞中达到抗病毒活性水平。我们的结果将SERINC5归类为非常规HIV-1限制因子，其表达在细胞向髓系谱系分化时被特异性诱导。
免疫学杂志