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B LYMPHOCYTES, BUT NOT DENDRITIC CELLS, EFFICIENTLY HIV-1 TRANS-INFECT NAÏVE CD4+ T CELLS: IMPLICATIONS FOR THE VIRAL RESERVOIR
bioRxiv - Microbiology Pub Date : 2020-10-23 , DOI: 10.1101/2020.10.22.351627
Abigail Gerberick , Diana C. DeLucia , Paolo Piazza , Mounia Alaoui-El-Azher , Charles R. Rinaldo , Nicolas Sluis-Cremer , Giovanna Rappocciolo

Insight into the establishment and maintenance of HIV-1 infection in resting CD4+ T cell subsets is critical for the development of therapeutics targeting the HIV-1 reservoir. Although the frequency of HIV-1 infection, as quantified by the frequency of HIV-1 DNA, is lower in CD4+ naïve T cells (TN) compared to the memory T cell subsets, studies have shown that TN cells harbor a large pool of replication-competent virus. However, TN cells are highly resistant to direct (cis) HIV-1 infection in vitro, in particular to R5-tropic HIV-1, as TN cells do not express CCR5. In this study, we investigated whether TN cells could be efficiently HIV-1 trans-infected by professional antigen-presenting B lymphocytes and myeloid dendritic cells (DC) in the absence of global T cell activation. We found that B cells, but not DC, have a unique ability to efficiently trans infect TN cells in vitro. In contrast, both B cells and DC mediated HIV-1 trans infection of memory and activated CD4+ T cells. Moreover, we found that TN isolated from HIV-1-infected nonprogressors (NP) harbor significantly disproportionately lower levels of HIV-1 DNA compared to TN isolated from progressors. This is consistent with our previous finding that APC derived from NP do not efficiently trans-infect CD4+ T cells due to alterations in APC cholesterol metabolism and cell membrane lipid raft organization. These findings support that B cell-mediated trans infection of TN cells with HIV-1 has a more profound role than previously considered in establishing the viral reservoir and control of HIV-1 disease progression.

中文翻译:

B淋巴细胞,而不是树突状细胞,有效感染HIV-1的天然CD4 + T细胞:对病毒贮库的影响

深入了解静息CD4 + T细胞亚群中HIV-1感染的建立和维持对于开发针对HIV-1储库的疗法至关重要。尽管与记忆T细胞亚群相比,CD4 +幼稚T细胞(T N)中HIV-1感染的频率(通过HIV-1 DNA的频率来量化)较低,但研究表明T N细胞具有大量的具有复制能力的病毒库。然而,T Ñ细胞是高度耐指导(顺式)HIV-1感染在体外,特别是R5向性HIV-1,为T Ñ细胞不表达CCR5。在这项研究中,我们调查了T N是否在没有整体T细胞活化的情况下,可以通过专业的抗原呈递B淋巴细胞和髓样树突细胞(DC)有效感染HIV-1细胞。我们发现B细胞而非DC具有独特的能力,可以在体外有效转染T N细胞。相反,B细胞和DC介导的HIV-1转染感染了记忆和活化的CD4 + T细胞。此外,我们发现,Ť ñ来自HIV-1感染的进展者(NP)分离怀有HIV-1 DNA的显著不成比例较低水平相比Ť ñ从进展者隔离。这与我们先前的发现一致,即来自NP的APC不能有效地转染CD4 +T细胞归因于APC胆固醇代谢和细胞膜脂质筏组织的改变。这些发现表明,在建立病毒库和控制HIV-1疾病进展中,B细胞介导的HIV感染T N细胞的反式感染比以前认为的具有更深远的作用。
更新日期:2020-10-27
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