Retrovirus in the human genome is active in pluripotent stem cells

January 23, 2013, University of Massachusetts Medical School

A retrovirus called HERV-H, which inserted itself into the human genome millions of years ago, may play an important role in pluripotent stem cells, according to a new study published in the journal Retrovirology by scientists at UMass Medical School. Pluripotent stem cells are capable of generating all tissue types, including blood cells, brain cells and heart cells. The discovery, which may help explain how these cells maintain a state of pluripotency and are able to differentiate into many types of cells, could have profound implications for therapies that would use pluripotent stem cells to treat a range of human diseases.

"What we've observed is that a group of endogenous retroviruses called HERV-H is extremely busy in ," said Jeremy Luban, MD, the David L. Freelander Memorial Professor in HIV/AIDS Research, professor of molecular medicine and lead author of the study. "In fact, HERV-H is one of the most abundantly expressed genes in pluripotent stem cells and it isn't found in any other cell types."

In the study, Dr. Luban and colleagues describe how RNA from the HERV-H sequence makes up as much as 2 percent of the total RNA found in pluripotent stem cells. The HERV-H sequence is controlled by the same factors that are used to reprogram into induced pluripotent stem (iPS) cells, a discovery that garnered the 2012 in Physiology or Medicine. "In other words, HERV-H is a new marker for in humans that has the potential to aid in the development of iPS cells and transform current stem cell technology," said Luban.

When a retrovirus infects a cell, it inserts its own genes into the chromosomal DNA of the host cell. As a result, the host cell treats the as part of its own DNA sequence and begins making the proteins required to assemble new copies of the virus. And because the retrovirus is now part of the host cell's genome, when the cell divides, the virus is inherited by all .

In rare cases, it's believed that retroviruses can infect human sperm or egg cells. If this happens, and if the resulting embryo survives, the retrovirus can become a permanent part of the human genome, and be passed down from generation to generation. Scientists estimate that as much as 8 percent of the human genome may be comprised of extinct retroviruses left over from infections that occurred millions of years ago. Yet these sequences of fossilized retrovirus were thought to have no discernible functional value.

"The human genome is filled with retrovirus DNA thought to be no more than fossilized junk," said Luban. "Increasingly, there are indications that these sequences might not be junk. They might play a role in gene expression after all."

An expert in HIV and other retroviruses, Luban and his colleagues were seeking to understand if there was a rationale behind where, in the expansive human genome, retroviruses inserted themselves. Knowing where along the chromosomal DNA retroviruses might attack could potentially lead to the development of drugs that protect against infection; better gene therapy treatments; or novel biomarkers that would predict where a retrovirus would insert itself in the genome, said Luban.

Turning these same techniques on the retrovirus sequences already in the human genome, they discovered a sequence, HERV-H, that appeared to be active. "The sequences weren't making proteins because they had been so disrupted over millions of years, but they were making these long, noncoding RNAs," said Luban.

Specifically, the HERV-H sequence was making abundant amounts of RNA in human —and only stem cells. In total, there are more than 1,000 HERV-H retrovirus genomes scattered throughout the human genome. The Luban lab also found high levels of HERV-H RNA in some iPS cells. Other iPS cells, perhaps those lines that were not sufficiently reprogrammed to pluripotency, had lower levels of the HERV-H RNA, another indication that HERV-H may be an important marker for pluripotency.

Interestingly, the HERV-H genes that were expressed in human are only found in the human and chimpanzee genomes, indicating that HERV-H infected a relatively recent ancestor to humans, said Luban.

"Once upon a time HERV-H was an invader to our genome and perhaps caused diseases like AIDS or cancer," said Luban. "Now it seems that a kind of détente has been reached. Not only that, but this ancient invader may one day be exploited by clinicians to cure people of a wide range of diseases using stem cell therapies."

Luban and colleagues will next try to determine the specific mechanisms by which HERV-H contributes to pluripotency.

Explore further: HIV-1 vaccine development: Pinning down a moving target

Related Stories

HIV-1 vaccine development: Pinning down a moving target

November 12, 2012
HIV-1 is a genetically diverse collection of viruses, making it a moving target in vaccine development.

Recommended for you

Everything big data claims to know about you could be wrong

June 19, 2018
When it comes to understanding what makes people tick—and get sick—medical science has long assumed that the bigger the sample of human subjects, the better. But new research led by UC Berkeley suggests this big-data ...

Are you sticking to your diet? Scientists may be able to tell from a blood sample

June 19, 2018
An analysis of small molecules called "metabolites" in a blood sample may be used to determine whether a person is following a prescribed diet, scientists at Johns Hopkins Bloomberg School of Public Health have shown.

Diagnosing and treating disorders of early sex development

June 19, 2018
Diagnosing, advising on and treating disorders of early sex development represent a huge medical challenge, both for those affected and for treating physicians. In contrast to the earlier view, DSD (Difference of Sex Development) ...

BPA can induce multigenerational effects on ability to communicate

June 18, 2018
Past studies have shown that biparental care of offspring can be affected negatively when females and males are exposed to bisphenol A (BPA); however, previous studies have not characterized how long-term effects of BPA exposure ...

New compound shown to be as effective as FDA-approved drugs against life-threatening infections

June 15, 2018
Purdue University researchers have identified  a new compound that in preliminary testing has shown itself to be as effective as antibiotics approved by the Food and Drug Administration to treat life-threatening infections ...

Foods combining fats and carbohydrates more rewarding than foods with just fats or carbs

June 14, 2018
Researchers show that the reward center of the brain values foods high in both fat and carbohydrates—i.e., many processed foods—more than foods containing only fat or only carbs. A study of 206 adults, to appear June ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

VendicarD
5 / 5 (1) Jan 23, 2013
No one tell the Creationists. They will soil their underpants.
IronhorseA
not rated yet Jan 23, 2013
No one tell the Creationists. They will soil their underpants.

Too late, they already did. Why do you think they walk funny ;P

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.