Equine lentivirus counteracts SAMHD1 restriction by Rev-mediated degradation of SAMHD1 via the BECN1-dependent lysosomal pathway

文献类型： 外文期刊

第一作者： Ren, Huiling

作者： Ren, Huiling;Yin, Xin;Su, Chao;Guo, Miaomiao;Wang, Xue-Feng;Na, Lei;Lin, Yuezhi;Wang, Xiaojun

作者机构：

关键词： BECN1; EIAV; HIV-1; innate immunity; lysosome; non-canonical autophagy; retrovirus; Rev; SAMHD1

期刊名称：AUTOPHAGY （ 影响因子：16.016； 五年影响因子：16.586 ）

ISSN： 1554-8627

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收录情况： SCI

摘要： The innate immune restriction factor SAMHD1 can inhibit diverse viruses in myeloid cells. Mechanistically, SAMHD1 inhibits lentiviral replication including HIV-1 by depleting the nucleotide pool to interfere with their reverse transcription. Equine infectious anemia virus (EIAV) is an ancient lentivirus that preferentially attacks macrophages. However, the mechanism by which EIAV successfully establishes infection in macrophages with functional SAMHD1 remains unclear. Here, we demonstrate that while equine SAMDH1 can limit EIAV replication in equine macrophages at the reverse transcription stage, the antiviral effect is counteracted by the well-known transcriptional regulator Rev, which downregulates equine SAMHD1 through the lysosomal pathway. Remarkably, Rev hijacks BECN1 (beclin 1) and PIK3C3 to mediate SAMHD1 degradation in a canonical macroautophagy/autophagy-independent pathway. Our study illustrates that equine lentiviral Rev possesses important functions in evading cellular innate immunity in addition to its RNA regulatory function, and may provide new insights into the co-evolutionary arms race between SAMHD1 and lentiviruses.

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