研究表明SARS-CoV-2可以改变人类细胞的基因组结构

 

概要

 

根据休斯顿大学研究人员的一项新研究，感染SARS-CoV-2的人可能会经历基因组结构的变化，这不仅可能解释人类感染后的免疫症状，而且还可能与“长新冠”有关。

人类细胞中的遗传物质被储存在一个叫做染色质的结构中。研究发现，正常细胞内许多原本结构良好的染色质会变形。例如，人体感染新冠病毒后，一种名为a/B区的染色质结构的阴阳两部分会开始混合在一起，这种混合可能导致被感染细胞内一些关键基因发生变化，其中包括关键的炎症基因白细胞介素-6，它会在新冠肺炎重症患者体内引起细胞因子风暴。

此外，这项研究还发现染色质上的化学修饰也被SARS-CoV-2改变了。已知染色质的化学修饰的变化对基因表达和表型产生了长期影响。因此，新发现可能为理解新冠病毒对宿主染色质的影响提供一个新视角，这种影响可能与“长新冠”有关。

据美国疾病控制和预防中心称，近五分之一的美国人感染了COVID-19，甚至在从急性感染恢复后的几个月内仍在遭受“长新冠”的侵扰。研究人员希望这些发现将为进行更多研究以了解该病毒的长期影响铺平道路。

 

Study: SARS-CoV-2, the virus causing COVID-19, can alter genome structure of our cells

 

People infected with SARS-CoV-2, the virus that causes COVID-19, may experience genome structure changes that not only may explain our immunological symptoms after infection, but also potentially link to long COVID, according to a new study by researchers at UTHealth Houston.

 

The study was published today in Nature Microbiology.

 

“This particular finding is quite unique and has not been seen in other coronaviruses before,” said Wenbo Li, PhD, senior author on the study and associate professor in the Department of Biochemistry and Molecular Biology with McGovern Medical School at UTHealth Houston. “What we found here is a unique mechanism of SARS-CoV-2 that is associated with its severe impacts on human health.”

 

The genetic materials in our cells are stored in a structure called chromatin. Some viruses of other categories have been reported to hijack or change our chromatin so that they can successfully reproduce in our cells. Whether and how SARS-CoV-2 may affect our chromatin was not known. In this study, researchers used leading-edge methods and comprehensively characterized the chromatin architecture in human cells after a COVID-19 infection.

 

“We found that many well-formed chromatin architectures of a normal cell become de-organized after infection. For example, there is one type of chromatin architecture termed A/B compartments that can be analogous to the yin and yang portions of our chromatin. After SARS-CoV-2 infection, we found that the yin and yang portions of the chromatin lose their normal shapes and start to mix together. Such mixing may be a reason for some key genes to change in infected cells, including a crucial inflammation gene interleukin-6 that can cause cytokine storm in severe COVID-19 patients,” Li said.

 

In addition, this work found that chemical modifications on chromatin were also altered by SARS-CoV-2. “The changes of chemical modifications of chromatin were known to exert long-term effects on gene expression and phenotypes. Therefore, our finding may provide an unrealized new perspective to understand the viral impacts on host chromatin that can associate with long COVID,” Yuan said.

 

Nearly 1 in 5 Americans infected with COVID-19 are still suffering from long COVID symptoms even months after recovery from acute infection, according to the Centers for Disease Control and Prevention. Researchers hope these findings will pave the way into more research to understand the long-term impacts of the virus.

 

“Groundbreaking research frequently requires that scientists from different backgrounds, with different expertise, and from different departments come together and join in answering cutting-edge research questions,” said Holger Eltzschig, MD, PhD, John P. and Kathrine G. McGovern Distinguished University Chair of the Department of Anesthesiology, Critical Care and Pain Medicine at McGovern Medical School. “The highly collaborative research environment at UTHealth Houston fosters these opportunities. The Center for Perioperative Medicine at McGovern Medical School at UTHealth Houston provided the platform for our experts in SARS-CoV-2 infections, lung injury, epigenetics, and biochemistry to pursue this transformative research work together.”

 

“This study elucidated to us how SARS-CoV-2 can uniquely alter our chromatin to cause COVID-19 symptoms. Future work will focus on understanding the mechanisms of how SARS-CoV-2 can achieve this. This will need to be done in both cell and animal models, and by using COVID-19 patients’ samples. Finding the mechanism will offer therapeutic strategies to safeguard our chromatin and to better fight this virus,” said Li.

 

Additional UTHealth Houston authors include: Xiaoyi Yuan, PhD; Ruoyu Wang, MS; Joo-Hyung Lee, PhD; Jieun Kim, PhD; Feng Xiong, PhD; Lana Al Hasani, BS; Yuqiang Shi, PhD; Erin N. Simpson, BS; Xiaoyu Zhu, PhD; Yi-Ting Chen, BS; Pooja Shivshankar, PhD; Joanna Krakowiak, PhD; and Yanyu Wang, PhD. David M. Gilbert, PhD, is with the San Diego Biomedical Research Institute.

 

Source:

UTHealth Houston

Published on March 23, 2023

 

 

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