Epstein–Barr virus promotes faster nasopharyngeal cancer growth

Singaporean and Japanese researchers have shown how the Epstein–Barr virus (EBV) tricks human cells into turning on specific genes that promote cancerous growth, making nasopharyngeal carcinoma (NPC) tumours grow faster. Their research has been published in the journal eBioMedicine.

The Epstein–Barr virus, also known as human herpesvirus 4, is one of the most common human viruses, causing infectious mononucleosis (glandular fever) and other illnesses. Although the virus does not always cause illness in humans, as our immune systems can quickly detect when it affects cells, it lays dormant in our bodies and primarily spreads between people through bodily fluids, particularly saliva.

Meanwhile, more than 130,000 new cases of NPC are diagnosed worldwide annually, with the majority occurring in South-East Asia, China and Northern Africa. Detection typically occurs late due to mild or non-specific early symptoms, resulting in delayed diagnosis, poorer prognosis and reduced treatment success rates. Now, through analysis of EBV-infected NPC cells as well as healthy nasopharyngeal cells obtained from 25 patients at Kanazawa University Hospital, the researchers have identified crucial mechanisms underlying the disease progression.

EBV’s genetic material typically remains inactive because it is not actively engaged in processes within its external environment. However, upon infecting a host cell, it encounters the necessary factors and conditions for the virus’s genetic material to become active. The virus then activates human genes that were previously switched off, causing cells to grow uncontrollably and form tumours.

“In cells, certain sections of the genetic material are actively involved in cell functions, while others remain dormant,” said study leader Associate Professor Melissa Jane Fullwood, from NTU Singapore. “Our research revealed that the Epstein–Barr virus attaches itself to these dormant sections within NPC cells. This abnormal attachment triggers the activation of these dormant sections, ultimately contributing to the development of NPC.”

Additionally, EBV can activate cellular DNA switches called ‘enhancers’, which regulate how genes are expressed. This activation leads to further abnormal gene activity, promoting the growth and development of NPC tumours. Furthermore, EBV’s interaction with the host’s genetic material promotes changes in the host’s DNA structure, activating both viral and host genes that contribute to tumour growth.

“We hypothesise that the idea of enhancer infestation, which rewires DNA structure and activates nearby genes, could offer new insight into how cancer forms,” said lead author Professor Atsushi Kaneda, from Chiba University. “This involves the interaction of viral DNA with changes in how DNA is arranged in cells, which might be important for many types of cancer, not just those linked to EBV.”

The researchers are currently discussing with pharmaceutical companies the potential development of therapies focusing on the genes that EBV targets in nasopharyngeal cells. Such treatments could include drugs or therapies that block the function of the genes that EBV activates, thereby preventing tumour growth or even killing cancer cells.

“[EBV’s] ability to interact with our cells and interfere with various diseases underscores the intricate relationship between viruses and human health,” Fullwood said. “Understanding how these microscopic viruses influence our biology opens pathways to comprehend the broader impact of viral infections on our wellbeing, paving the way for new insights into disease prevention and treatment.”

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