HIV-1 tracing method of systemic viremia in vivo using an artificially mutated virus pool

HIV-1 tracing method of systemic viremia in vivo using an artificially mutated virus pool
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使用人工突变病毒库的体内系统性病毒血症的HIV-1追踪方法

DOI:
10.1111/1348-0421.12862
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发表时间:
2021
影响因子:
2.6
通讯作者:
Kei Sato
Kei Sato
中科院分区:
医学4区
文献类型:
--
作者:
Andrew Soper;Yoshio Koyanagi;Kei Sato

文献摘要

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人类免疫缺陷病毒1型(HIV-1)血浆病毒血症的出现与症状性疾病的进展和CD 4 +T细胞耗竭相关。为了定位系统性病毒血症的来源,该研究采用了一种新的方法来追踪体内HIV-1感染。我们通过随机诱变PCR创建了具有高度突变nef基因区域的感染性HIV-1(毒株JR-CSF)库JRCSF nef,并将该突变病毒库感染到Jurkat-CCR 5细胞和造血干细胞移植的人源化小鼠中。感染导致人源化小鼠的全身性血浆病毒血症,病毒RNA测序帮助我们鉴定多个淋巴器官,如脾、淋巴结和骨髓,而不是外周血细胞作为全身性病毒血症的来源。我们的数据表明,这种方法可能是有用的,在体内追踪病毒贩运。
The appearance of human immunodeficiency virus type 1 (HIV‐1) plasma viremia is associated with progression to symptomatic disease and CD4+T cell depletion. To locate the source of systemic viremia, this study employed a novel method to trace HIV‐1 infection in vivo. We created JRCSFξnef, a pool of infectious HIV‐1 (strain JR‐CSF) with highly mutatednefgene regions by random mutagenesis PCR and infected this mutated virus pool into both Jurkat‐CCR5 cells and hematopoietic stem cell‐transplanted humanized mice. Infection resulted in systemic plasma viremia in humanized mice and viral RNA sequencing helped us to identify multiple lymphoid organs such as spleen, lymph nodes, and bone marrow but not peripheral blood cells as the source of systemic viremia. Our data suggest that this method could be useful for the tracing of viral trafficking in vivo.