Infection with Vaccinia Virus (above) was used to test the effect of deleting MER41 ERVs on the cell's immune response ()
Infection with Vaccinia virus (above) was used to test the effect of deleting MER41 ERVs on the cell’s immune response (Photo Credit:Content Providers(s): CDC/Cynthia Goldsmith [Public domain], via Wikimedia Commons)

Scientists have estimated that there are 10 to the power of 31 viruses on Earth, but humans don’t just live in a viral world, we are also part virus ourselves. 8% of the human genome is derived from viruses and these endogenous retroviruses (ERVs) represent ancient viral infections that became integrated into the human genome. Scientists had previously known the importance of a specific ERV in the development of the placenta, but now they have discovered a subset of ERVs that help regulate our immune system.

When a cell gets infected it releases chemical signals called interferons (IFN) that will stimulate the expression of certain genes that are important for mounting an immune response against the invading pathogen. A number of ERVs from the MER41 family were found adjacent to several of these immune response genes, increasing their expression. When these ERVs were deleted using a gene-editing system (CRISPR-Cas9), the expression of these IFN-stimulated genes was decreased and, in the case of one ERV (MER41.AIM2) the mutant cell’s ability to mount an inflammatory response following viral infection was markedly reduced.

When we look at both this new function of ERVs in immune regulation and consider that ERVs make up 8% of the human genome, the obvious next question is what are all these ERVs doing? For instance, in the case of the 18 intact ERV envelope open reading frames in the genome, “only three are competent for fusion” according to Joe Timpona. As for the other 15? “They could be involved in signaling, but they could also be involved in receptor blocking by occupying receptors used by exogenous retroviruses.”

There’s clearly a lot of research still to be done in the field of ERVs, but the discovery that they can help muster our immune response to extant viruses encourages continued research into finding other examples of ancient rogue viruses gone good.



Special thanks to Joe Timpona, a graduate student in the Virology Program at Harvard who studies endogenous viral envelope proteins, for his time and commentary.

Original Article

Edward Chuong et al.’s Regulatory evolution of innate immunity through co-option of endogenous retroviruses (Science)

Further Reading

Sarah Zhang’s Ancient Viruses Hidden in Your DNA Fight Off New Viruses (Wired)

Managing Correspondent

Fernanda Ferreira

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