The Dawn of the Retroviruses–in Human Embryos

Human blastocyst (early embryo) produces virus-like particles (green)

We’ve discussed before how ancient endogenous retroviruses evolved into our own human genes, including HERVs (human endogeount retroviral genes) that encode essential products such as placental syncitin. So far, though, it has been assumed that the viruses themselves were extinct; that only their nucleobase sequence (ATCG etc.) remained, adapted to a human function.

Now, researchers show that human embryos produce actual virions–virus particles–containing retroviral sequence and capsid. These truly endogenous retrovirus particles actually serve as part of the human immune system to protect us from viral infection. This is, bizarrely enough, the very opposite of what HIV (the most famous retrovirus) does to adult human immune systems.

The retrovirus studied was HERVK, which infected humans while we were still diverging from chimps–relatively recently in our evolution. Multiple infections left signs of their nucleobase sequence in our genome; in fact, since humans show different versions of HERVK in their genomes toda, the virus must continue some activity in our population, in the last 200,000 years. Thus, HERVK would be a good bet to exhibit some virus-producing ability. At Stanford, Joanna Wysocka and colleagues used fluorescence microscopy and various specific fluorophores (glowing molecules that bind specific proteins or genes) to show the presence of HERVK virus-like particles emerging from embryos.

Why embryos? In adult humans, HERVK appears to be suppressed by DNA methylation, a chemical modification of the nucleobases that generally turns of gene expression (the making of a gene’s product). But in the embryos, the HERVK DNA is free of methyl groups. So, the embryo condition allows expression of retroviral genes. The gene expression is not random, but is regulated by known embryonic regulators, such as the OCT4 transcription factor. The OCT4 is known as a gene expressed only during very early embryos–or in tumors, under abnormal conditions.

Surprisingly, the HERVK activation leads to production of virus-like particles (particles that look like viruse under electron microscopy). Even more surprising, HERVK activation causes upregulation of the anti-viral defense protein, Interferon-induced transmembrane protein 1 (IFITM1). Interferons are a class of protein that host cells commonly express in response to being infected–to tell their neighbor cells to avoid infection. In this case, however, the HERVK may be protecting the embryos from infection of other possible pathogens during a vulnerable period in the womb, before the adult immune system develops.

You may be wondering, where do the researchers get all these human embryos to study? Early human embryos at the stage of blastocyst (hollow ball of cells) are obtained from IVF donors; couples who seek in vitro fertilization for reasons of infertility or other causes. The IVF procedure routinely produces “supernumerary” embryos, a fancy word for “more than needed.” Such embryos are commonly donated to science, under government regulation.