Endogenous retroviruses and disease

Did you know that there are retroviruses in the human genome? In fact, there are retroviruses in the genome of all mammals. These viruses have previously integrated their DNA into our ancestors’ DNA, and have degraded to the point that they can no longer replicate and infect other cells. However, they still contain some of the characteristics of retroviruses, such as long terminal repeat (LTR) regions and gag, pol, and env genes. [1]

It has been suggested that these human endogenous retroviruses (HERVs) may modulate gene expression. [1] For example, the release of amylase into saliva may be regulated by a HERV that acts as a promoter, and apolipoprotein C1 (a protein that helps with lipid transport) may be regulated by a LTR from a HERV. [2]

Interestingly, some proteins derived from HERVs are also used by the human body, such as syncytin-1 and 2, which originate from env genes (which code for proteins in retroviral envelopes). Syncytins are responsible for cell fusion and are especially important in placental development. [2]

HERVs may also modulate our immune system: proteins coded from HERV DNA may bind to pattern recognition receptors and stimulate innate immune responses, which may be involved in autoimmune diseases and cancer. [3] This also may be a potential therapeutic target: currently, there are human trials using antibodies against HERV proteins in multiple sclerosis and type 1 diabetes. [3] However, HERV proteins may also have immunosuppressive roles: Env proteins such as the aforementioned syncytin-2 may prevent immune responses from the mother against the fetus during pregnancy. [3]

The role of HERVs in the human body is complex and there is much room for discovery. Although it has been speculated that HERVs may have roles in some cancers and neurodegenerative diseases, the evidence is not yet conclusive. [2] The roles of transposable elements in human gene regulation and disease is still an ongoing research topic, and it is a constant reminder that our genome isn’t as static as we once thought.

Sources:
1. Nelson PN, Hooley P, Roden D, et al. Human endogenous retroviruses: transposable elements with potential ? Clin Exp Immunol. 2004;138(1):1-9. doi:10.1111/j.1365-2249.2004.02592.x

2. Jern P, Coffin JM. Effects of Retroviruses on Host Genome Function. Annu Rev Genet. 2008;42(1):709-732. doi:10.1146/annurev.genet.42.110807.091501

3. Grandi N, Tramontano E. Human Endogenous Retroviruses Are Ancient Acquired Elements Still Shaping Innate Immune Responses. Front Immunol. 2018;9. doi:10.3389/fimmu.2018.02039

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