Advances in Model Systems for Human Cytomegalovirus Latency and Reactivation.

Advances in Model Systems for Human Cytomegalovirus Latency and Reactivation.
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DOI:
10.1128/mbio.01724-21
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发表时间:
2022-02-22
期刊:
影响因子:
6.4
通讯作者:
Hancock MH
Hancock MH
中科院分区:
生物学1区
文献类型:
--
作者:
Crawford LB;Diggins NL;Caposio P;Hancock MH

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人巨细胞病毒(HCMV)是一种高度流行的β-疱疹病毒,是造血和实体器官移植后发病和死亡的重要原因,也是先天性畸形的主要病毒原因。HCMV发病机制的一个关键特征是病毒能够在造血祖细胞和骨髓谱系细胞中建立潜伏感染。HCMV潜伏期的研究一直受到阻碍的困难,在获得和培养的原代细胞,以及无法定量测量再活化病毒,但最近的进展,在体外和体内模型的HCMV潜伏期和再活化导致宿主和病毒之间的相互作用有了更大的了解。建立的模型系统中的关键差异也导致了围绕病毒基因产物在潜伏期建立、维持和再激活中的作用的争议。这篇综述将讨论各种模型的细节和挑战,包括造血祖细胞,单核细胞,细胞系和人源化小鼠。我们强调了这些模型之间的实用性和功能差异,以及定义潜伏期和再激活所需的必要实验设计,这将有助于更完整地了解HCMV感染骨髓系细胞的情况。
Human cytomegalovirus (HCMV) is a highly prevalent beta-herpesvirus and a significant cause of morbidity and mortality following hematopoietic and solid organ transplant, as well as the leading viral cause of congenital abnormalities. A key feature of the pathogenesis of HCMV is the ability of the virus to establish a latent infection in hematopoietic progenitor and myeloid lineage cells. The study of HCMV latency has been hampered by difficulties in obtaining and culturing primary cells, as well as an inability to quantitatively measure reactivating virus, but recent advances in both in vitro and in vivo models of HCMV latency and reactivation have led to a greater understanding of the interplay between host and virus. Key differences in established model systems have also led to controversy surrounding the role of viral gene products in latency establishment, maintenance, and reactivation. This review will discuss the details and challenges of various models including hematopoietic progenitor cells, monocytes, cell lines, and humanized mice. We highlight the utility and functional differences between these models and the necessary experimental design required to define latency and reactivation, which will help to generate a more complete picture of HCMV infection of myeloid-lineage cells.
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