CD71+ erythroid cells (CECs) have a wide range of immunomodulatory properties. Here, we show that CECs are expanded in the peripheral blood of HIV patients, with a positive correlation between their frequency and the plasma viral load. CECs from HIV patients and human cord blood/placenta exacerbate HIV-1 infection/replication when cocultured with CD4+ T cells, and that preexposure of CD4+ T cells to CECs enhances their permissibility to HIV infection. However, mature red blood cells (RBCs) do not enhance HIV replication when cocultured with CD4+ T cells. We also found CECs express substantial levels of the NOX2 gene and via a mitochondrial reactive oxygen species (ROS)-dependent mechanism possibly upregulate NF-κB in CD4+ T cells once cocultured, which affects the cell cycle machinery to facilitate HIV-1 replication. The complement receptor-1 (CD35) and the Duffy antigen receptor for chemokines (DARC) as potential HIV target molecules are expressed significantly higher on CECs compared to mature red blood cells. Blocking CD35 or DARC substantially abolishes HIV-1 transmission by RBCs to uninfected CD4+ T cells but not by CECs. In contrast, we observed CECs bind to HIV-1 via CD235a and subsequently transfer the virus to uninfected CD4+ T cells, which can be partially blocked by the anti-CD235a antibody. More importantly, we found that CECs from HIV-infected individuals in the presence of antiretroviral therapy harbor infective viral particles, which mediate HIV-1 trans-infection of CD4+ T cells. Therefore, our findings provide a novel insight into the role of CECs in HIV pathogenesis as potential contributing cells in viral persistence and transmission.IMPORTANCE Immature red blood cells (erythroid precursors or CD71+ erythroid cells) have a wide range of immunomodulatory properties. In this study, we found that these erythroid precursors are abundant in the human cord blood/placental tissues, in the blood of HIV-infected and anemic individuals. We observed that these cells exacerbate HIV-1 replication/infection in target cells and even make HIV target cells more permissible to HIV infection. In addition, we found that HIV gets a free ride by binding on the surface of these cells and thus can travel to different parts of the body. In agreement, we noticed a positive correlation between the plasma viral load and the frequency of these cells in HIV patients. More importantly, we observed that infective HIV particles reside inside these erythroid precursors but not mature red blood cells. Therefore, these cells by harboring HIV can play an important role in HIV pathogenesis.

中文翻译：

---

CD71 +红系细胞加剧了HIV-1的易感性，介导了转染和港口感染性病毒颗粒。

CD71 +红系细胞（CEC）具有广泛的免疫调节特性。在这里，我们显示CECs在HIV患者的外周血中扩增，其频率与血浆病毒载量之间呈正相关。与CD4 + T细胞共培养时，来自HIV患者和人脐带血/胎盘的CEC加重了HIV-1的感染/复制，而CD4 + T细胞与CEC的预接触增加了其对HIV感染的容许性。但是，成熟的红细胞（RBC）与CD4 + T细胞共培养时，不会增强HIV复制。我们还发现CECs表达大量NOX2基因，并且通过线粒体活性氧（ROS）依赖性机制可能在共培养后上调CD4 + T细胞中的NF-κB，从而影响细胞周期机制以促进HIV-1复制。与成熟的红细胞相比，CEC上的补体受体-1（CD35）和趋化因子的达菲抗原受体（DARC）作为潜在的HIV靶分子在CEC上的表达明显更高。阻断CD35或DARC可以基本上消除RBC向未感染的CD4 + T细胞的HIV-1传播，但不能消除CEC。相反，我们观察到CEC通过CD235a与HIV-1结合，随后将病毒转移至未感染的CD4 + T细胞，该细胞可被抗CD235a抗体部分阻断。更重要的是，我们发现在存在抗逆转录病毒疗法的情况下，来自HIV感染者的CEC带有感染性病毒颗粒，这些颗粒介导CD-1 + T细胞的HIV-1转染。因此，我们的发现提供了对CEC在HIV发病机理中作为病毒持久性和传播中潜在贡献细胞的作用的新颖见解。重要信息未成熟的红细胞（类红细胞前体或CD71 +红细胞）具有广泛的免疫调节特性。在这项研究中，我们发现这些类红细胞前体在人类脐带血/胎盘组织，HIV感染者和贫血者的血液中丰富。我们观察到这些细胞加剧了靶细胞中HIV-1的复制/感染，甚至使HIV靶细胞更容易感染HIV。此外，我们发现，HIV通过结合在这些细胞的表面上而不受约束，因此可以传播到身体的不同部位。一致地，我们注意到血浆中病毒载量与HIV患者中这些细胞的频率之间呈正相关。更重要的是，我们观察到感染性HIV颗粒位于这些类红细胞前体内部，但不存在成熟的红细胞。因此，