Chromosome state compromised after viral infection

By ELAINE CHIAO | March 8, 2018

An oncovirus is a type of virus with a DNA or RNA genome that can cause cancer. 

When viruses inject their own genes into a human host and their DNA begins to replicate within the host, these viruses catalyze a process that edits specific parts of the human genome in a unique, and oftentimes deleterious, way.

Recently, a review published by the University of Colorado (CU) Cancer Center in the journal Viruses suggested a possible route for viruses to promote cancer.

Viruses, researchers at CU claimed, inactivate the immune system through an epigenetic regulation called DNA methylation. 

Epigenetics is a way to alter the level of gene expression without fundamentally changing the encoded DNA sequence. More specifically, epigenetic changes such as DNA methylation can add modifications to proteins bound to the genome, causing genes on that chromosome to be activated or silenced to particular degrees.

Viruses cause methylation of promoter regions in a gene, which act as on-and-off switches for their neighboring genes. When promoter sequences in the DNA are silenced, genes that are located next to them are incapable of being expressed.

Sharon Kuss-Duerkop, a research instructor working in Dohun Pyeon’s lab at CU Cancer Center, explained the situation they observed and stated that gene silencing causes less protein to be created in the cell.

Viruses do not directly add methyl groups to DNA on their own, at least. Rather, their entry into the body triggers the recruitment of a specific category of human proteins called DNA methyltransferases that do the job for them. 

What genes would viruses prefer to methylate and why? 

It might seem clear that these tiny agents would seek to turn off the genes that are required for the immune system to fight off viral intrusions. Some examples might include an anti-viral gene called interferon-b that is expressed in essentially all cell types or genes that are required by T cells to recognize viral infected cells.

Such a phenomenon certainly does not lead to beneficial changes. As a result of the methylation activity, the human immune system is often less competent in fighting off viruses, and newly formed tumors are subsequently able to evade the immune system’s detection.

Researchers are now looking for a way to use this knowledge to their advantage. Knowing that viruses can weaken the immune system against attacking cancers they cause, researchers aim to reciprocally activate the immune system toward these cancers.

Unfortunately, there are still many challenges that stand in the way between immunotherapy and cancer cure. Namely, every patient presents a unique case, and there is simply not a single therapy that can be effective for everyone.

Additionally, researchers have not been able to accurately determine the evolutionary characteristics of viruses that allow them to evade the immune system. With this understanding, researchers might one day be able to pinpoint which patients are more likely to be cured by immunotherapy.

Some people might propose using a technique that can erase all methylation sites in the genome, including many of the virally induced methylations. 

However, the application of this suggestion could likely result in the overexpression of many once-methylated genes and thus would not be a productive way of combating viral influences.

Instead, Kuss-Duerkop has another idea in mind. He speculated that proper functions of the immune system can be reestablished through demethylating certain promoter regions in the DNA sequence.

Noah Yan, a sophomore at Hopkins majoring in molecular and cellular biology, wrote in an email to The News-Letter that he found this research topic to be particularly interesting.

“Personally, I’m curious about which genes these viruses target. In my research, we have been working with cancer cells implanted in vivo, and the immune system often gets in the way when we are trying to grow large tumors in mice,” Yan wrote.

The discoveries made by Pyeon’s lab gave researchers worldwide a more comprehensive understanding of the effects of an oncoviral intrusion on the immune system. In the near future, this new understanding might play an important role in helping scientists learn how the body can harness enough of its own strength in order to effectively fight cancer. 

Ultimately, the end goal of the research team at the University of Colorado is to improve the effectiveness of immune-based therapies against cancer. 

“Ultimately viruses are causing these tumors to form and are further manipulating the immune system to allow tumors to keep growing,” Kuss-Duerkop said, according to ScienceDaily. “But these same mechanisms may be key in combating tumors with immune-based therapies or in keeping cancer from developing in the first place.”

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