P-selectin glycoprotein ligand-1 (PSGL-1/CD162) is incorporated into clinical HIV-1 isolates and can mediate virus capture and subsequent transfer to permissive cells.
P-selectin glycoprotein ligand-1 (PSGL-1/CD162) is incorporated into clinical HIV-1 isolates and can mediate virus capture and subsequent transfer to permissive cells.
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DOI：
10.1186/s12977-022-00593-5
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发表时间：
2022-05-21
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影响因子：
3.3
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中科院分区：
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P-选择素糖蛋白配体-1（PSGL-1/CD 162）因其通过与其同源受体P-选择素相互作用介导白细胞滚动的作用而被广泛研究。最近，PSGL-1被鉴定为一种新的HIV-1宿主限制因子，特别是当在HIV包膜中高水平表达时。重要的是，虽然PSGL-1的有效抗病毒活性已在各种互补模型系统中得到明确证明，但PSGL-1在遗传多样性病毒分离株和临床分离株中的掺入广度尚未得到描述。此外，病毒体掺入的PSGL-1的生物活性也尚未显示。在此，我们评估了通过用不同量的PSGL-1质粒DNA（0-250 ng）转染产生的病毒上的PSGL-1水平，与通过感染T细胞系和原代PBMC产生的病毒上的PSGL-1水平进行比较。我们发现，极低水平的PSGL-1质粒DNA（<2.5ng/孔）对于产生可以密切反映通过感染T细胞和PBMC产生的病毒表型的病毒模型是必需的。这项研究的独特之处在于，我们发现PSGL-1被纳入了广泛的HIV-1和SIV分离株中，并且在病毒血症HIV-1感染者的血浆中可检测到PSGL-1病毒粒子，证实了PSGL-1与自然感染的相关性。此外，我们表明病毒上的PSGL-1可以结合其同源选择素受体，P-，E-和L-选择素。最后，我们发现具有内源性PSGL-1水平的病毒可以被P-选择素捕获并转移到HIV允许的旁观者细胞，突出了PSGL-1在HIV-1感染中的新作用。值得注意的是，含有高水平PSGL-1的病毒在我们手中是无感染性的，这与先前报道PSGL-1的有效抗病毒活性的发现一致。我们的研究结果表明，PSGL-1纳入病毒体的水平可以有很大的不同模型系统测试，并仔细剪裁质粒水平时，需要使用假病毒模型重演生理系统。综上所述，我们的数据表明，PSGL-1可能发挥不同的作用，在HIV-1感染的生理，特别是由于PSGL-1的功能活性状态的病毒体表面和广泛的PSGL-1的掺入范围广泛的病毒分离株。在线版本包含补充材料，可通过10.1186/s12977-022-00593-5获得。
P-selectin glycoprotein ligand-1 (PSGL-1/CD162) has been studied extensively for its role in mediating leukocyte rolling through interactions with its cognate receptor, P-selectin. Recently, PSGL-1 was identified as a novel HIV-1 host restriction factor, particularly when expressed at high levels in the HIV envelope. Importantly, while the potent antiviral activity of PSGL-1 has been clearly demonstrated in various complementary model systems, the breadth of PSGL-1 incorporation across genetically diverse viral isolates and clinical isolates has yet to be described. Additionally, the biological activity of virion-incorporated PSGL-1 has also yet to be shown. Herein we assessed the levels of PSGL-1 on viruses produced through transfection with various amounts of PSGL-1 plasmid DNA (0–250 ng), compared to levels of PSGL-1 on viruses produced through infection of T cell lines and primary PBMC. We found that very low levels of PSGL-1 plasmid DNA (< 2.5 ng/well) were necessary to generate virus models that could closely mirror the phenotype of viruses produced via infection of T cells and PBMC. Unique to this study, we show that PSGL-1 is incorporated in a broad range of HIV-1 and SIV isolates and that virions with incorporated PSGL-1 are detectable in plasma from viremic HIV-1-infected individuals, corroborating the relevance of PSGL-1 in natural infection. Additionally, we show that PSGL-1 on viruses can bind its cognate selectin receptors, P-, E-, and L-selectins. Finally, we show viruses with endogenous levels of PSGL-1 can be captured by P-selectin and transferred to HIV-permissive bystander cells, highlighting a novel role for PSGL-1 in HIV-1 infection. Notably, viruses which contained high levels of PSGL-1 were noninfectious in our hands, in line with previous findings reporting the potent antiviral activity of PSGL-1. Our results indicate that levels of PSGL-1 incorporation into virions can vary widely among model systems tested, and that careful tailoring of plasmid levels is required to recapitulate physiological systems when using pseudovirus models. Taken together, our data suggest that PSGL-1 may play diverse roles in the physiology of HIV-1 infection, particularly due to the functionally active state of PSGL-1 on virion surfaces and the breadth of PSGL-1 incorporation among a wide range of viral isolates. The online version contains supplementary material available at 10.1186/s12977-022-00593-5.
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DOI：
10.3390/v12111296
发表时间：
2020-11-12
期刊：
Viruses
影响因子：
--
作者：
Burnie J;Tang VA;Welsh JA;Persaud AT;Thaya L;Jones JC;Guzzo C
通讯作者：
Guzzo C
影响因子：
7.3
作者：
Hobbs SJ;Nolz JC
通讯作者：
Nolz JC
影响因子：
3.7
作者：
Bonar, Michal M.;Tilton, John C.
通讯作者：
Tilton, John C.
影响因子：
4.6
作者：
Arakelyan A;Fitzgerald W;Zicari S;Vanpouille C;Margolis L
通讯作者：
Margolis L
DOI：
10.1073/pnas.1207314109
发表时间：
2012-06-12
影响因子：
11.1
作者：
Auerbach, David J.;Lin, Yin;Lusso, Paolo
通讯作者：
Lusso, Paolo