Fibrocytes differ from macrophages but can be infected with HIV-1

Fibrocytes (fibroblastic leukocytes) are recently identified as unique hematopoietic cells with features of both macrophages and fibroblasts. Fibrocytes are known to contribute to the remodeling or fibrosis of various injured tissues. However, their role in viral infection is not fully understood. Here we show that differentiated fibrocytes are phenotypically distinguishable from macrophages but can be infected with HIV-1. Importantly, fibrocytes exhibited persistently infected cell-like phenotypes, the degree of which was more apparent than macrophages. The infected fibrocytes produced replication-competent HIV-1, but expressed HIV-1 mRNA at low levels and strongly resisted HIV-1-induced cell death, which enabled them to support an extremely long-term HIV-1 production at low but steady levels. More importantly, our results suggested that fibrocytes were susceptible to HIV-1 regardless of their differentiation state, in contrast to the fact that monocytes become susceptible to HIV-1 after the differentiation into macrophages. Our findings indicate that fibrocytes are the previously unreported HIV-1 host cells, and suggest the importance of considering fibrocytes as one of long-lived persistently infected cells for curing HIV-1. To find the surface maker for fibrocyte and to analyze why fibrocyte show low HIV-1 replication we done the microarray analysis between fibrocyte(EA1065_65), macrophage(EA1065_02), fibrocyte infected with HIV-1 at Day12(EA1168_08) and macrophage infected with HIV-1 at Day3(EA1168_02).

纤维细胞（fibrocytes，又称成纤维样白细胞）是近年来被发现的一类独特造血细胞，兼具巨噬细胞与成纤维细胞的特征。现有研究表明纤维细胞可参与多种受损组织的重塑与纤维化过程，但其在病毒感染中的作用尚未完全阐明。本研究证实，分化成熟的纤维细胞在表型上与巨噬细胞存在显著差异，但可被人类免疫缺陷病毒1型（HIV-1）感染。尤为关键的是，纤维细胞呈现出持续性感染细胞的表型，且该表型的显著程度高于巨噬细胞。受感染的纤维细胞可产生具有复制能力的HIV-1，但其HIV-1信使核糖核酸（mRNA）的表达水平较低，且可强烈抵抗HIV-1诱导的细胞死亡，这使其能够以低水平但稳定的状态长期持续产生HIV-1。更为重要的是，本研究结果显示，纤维细胞无论处于何种分化状态，均对HIV-1易感；而单核细胞需分化为巨噬细胞后才会获得HIV-1易感性，二者形成鲜明对比。本研究结果表明，纤维细胞是此前尚未被报道的HIV-1宿主细胞，同时提示在HIV-1治愈研究中，需将纤维细胞纳入长期持续性感染细胞的考量范畴。为筛选纤维细胞的表面标志物并解析其HIV-1复制水平较低的原因，本研究对以下四组样本开展了微阵列分析：纤维细胞（EA1065_65）、巨噬细胞（EA1065_02）、感染HIV-1第12天的纤维细胞（EA1168_08）以及感染HIV-1第3天的巨噬细胞（EA1168_02）。