Viruses have taken the spotlight in recent years, no matter how much we want them gone. We normally think of these agents as something dangerous and harmful, which is not always true. There are many many viruses that have benefitted humanity, such as ancient retroviral DNA integrated into our genome that helps us get rid of other viruses (Frank, et al. 2022).
Before diving in, it is important to understand what retroviruses are and how we have viral DNA in our genomes. Retroviruses are viruses that use RNA as their genetic material (Nisole and Saib 2004). First, the virus must enter the cell through endocytosis (entering the cell using membrane interactions), then the capsule is broken down to reveal the RNA. The host cell converts the viral RNA into DNA using reverse transcriptase (an enzyme that turns RNA into DNA) and integrates it into its genome (Stake, et al. 2013). Once integrated into the genome, the host transcribes the proviral DNA as its own and produces viral proteins, which self-assemble into viruses. This is similar to the lysogenic cycle of viruses; however, the mechanisms are not the same, as seen in Figure 1.
Endogenous retroviruses (ERVs) are found in abundance in primate genomes (especially humans) and descended from ancient germline (reproductive cells) infections (Frank, et al. 2022). Exogenous retroviruses are normally transmitted horizontally and cause disease, however, Human ERVs (HERVs) can affect both somatic (all other non-reproductive cells) and germline cells. This also means that HERVs are transmitted vertically (Frank, et al. 2022). Vertical transmission is actually beneficial in this case because some of the DNA integrated into the human genome codes for a protein called suppressyn. This protein is excreted from immune cells and interacts with cells in its environment (Sugimoto, et al. 2013).
Suppressyn is a protein that has the ability to bind to the amino acid transporter ASCT2 (Sugimoto, et al. 2013). This is also the receptor for a diverse group of retroviruses, including HERVs, and exogenous viruses such as RD-114. To prove this, Frank et al. (2022) used feline placental cells and embryonic stem cells with high expression of suppresyn and exposed them to RD-114, a retrovirus that naturally infects felines. They found that these cells were not infected by the virus, whereas, other cells not expressing suppressyn got infected (Frank, et al. 2022). Then the authors experimentally depleted suppressyn from the placental and embryonic cells and exposed them to RD-114. Once exposed, the cells were infected by RD-114 (Frank, et al. 2022). An important result is that when the authors experientially introduced Suppressyn into cells that did not normally express the protein, they became resistant to RD-114 (Frank, et al. 2022). An example of its mechanism of action is shown in Figure 2.
Despite the fact that the studies were completed with feline tissues, the results are still important regarding the protection against viruses. Suppressyn is found in many mammalian genomes, including humans (Frank, et al. 2022), which indicates that we possibly use viral elements to resist other viruses. Researchers are still investigating other proteins like suppressyn as therapeutic agents. Perhaps one day, the viruses can get the credit they deserve for helping us to survive.
Works Cited
Anon. 2022. BioRender. [online] Available at: <https://app.biorender.com/illustrations/6369822d520bfdd2caa92ff8> [Accessed 7 November 2022].
Frank, J.A., Singh, M., Cullen, H.B., Kirou, R.A., Benkaddour-Boumzaouad, M., Cortes, J.L., Garcia Pérez, J., Coyne, C.B. and Feschotte, C., 2022. Evolution and antiviral activity of a human protein of retroviral origin. Science, 378(6618), pp.422–428. https://doi.org/10.1126/science.abq7871.
Nisole, S. and Saïb, A., 2004. Early steps of retrovirus replicative cycle. Retrovirology, 1, p.9. https://doi.org/10.1186/1742-4690-1-9.
Stake, M.S., Bann, D.V., Kaddis, R.J. and Parent, L.J., 2013. Nuclear Trafficking of Retroviral RNAs and Gag Proteins during Late Steps of Replication. Viruses, 5(11), pp.2767–2795. https://doi.org/10.3390/v5112767.
Sugimoto, J., Sugimoto, M., Bernstein, H., Jinno, Y. and Schust, D., 2013. A novel human endogenous retroviral protein inhibits cell-cell fusion. Scientific Reports, 3(1), p.1462. https://doi.org/10.1038/srep01462.