Ancient viral remnants in the human genome are active in healthy and diseased tissues, limiting their use as disease indicators, according to a study by Aidan Burn at Tufts University in Boston, USA and colleagues published today in PLOS Biology.

Human endogenous retroviruses (HERV), which are the genetic remains of extinct viruses, make up around 8% of the human genome and can permanently integrate viral genes into the host genome if they infect sperm or egg cells.

Various HERVs still have complete genes even though they are no longer contagious, and the generation of HERV RNA transcripts in human cells has been associated with some cancers.

However, nothing is known about how HERV expresses itself in healthy tissues. Researchers examined the presence of transcripts from a recent HERV subgroup, HML-2, in healthy tissues using RNA sequence data from the Genotype Tissue and Expression project to fill this information gap.

This collection contains information on gene expression in 54 different tissue types from about 1000 people. All tissue types have HML-2 transcripts, however the cerebellum, pituitary, testis, and thyroid tissues had the highest quantities.

These findings have significant clinical significance since they show that HML-2 activity is not restricted to unhealthy or malignant cells.

For instance, background expression in healthy tissues would need to be taken into consideration when using HML-2 expression as a cancer biomarker or therapeutic target.

The authors note that the expression levels of more ancient HML-2 viruses were highest in human tissues, suggesting that cells may suppress the activity of younger, less-degraded HERV fragments that include entire protein-coding sequences to avoid the synthesis of dangerous viral proteins.

The principal author, John Coffin, writes, “we have found that nearly all normal human tissues express, in their RNA, one or another of about three dozen endogenous proviruses, remnants of widespread retrovirus infection of our distant ancestors. 

They “expect this finding to provide a basis for further studies to understand the role of these elements in human biology and disease.”

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