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.

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