Sunday, 3 February 2013

Endogenous retroviruses and the placenta

Turnover of syncytiotrophoblast in a human placental villus

Syncytiotrophoblast lacks inner cell boundaries but contains multiple nuclei. One place where it occurs is the surface of human placental villi. Syncytiotrophoblast has a high turnover rate and is continually replenished from the cytotrophoblast. This requires fusion of cytotrophoblasts with the existing syncytiotrophoblast, a process promoted by syncytins.

Syncytins are genes of retroviral origin that have been incorporated into the genome and are expressed in the placenta where they promote cell fusion to form the multinucleated syncytiotrophoblast. As recently reviewed in Placenta, syncytins have been discovered in primates, muroid rodents (such as the mouse), rabbits and carnivores. The search continues.

A retrovirus is an RNA virus that replicates in a host cell. It uses reverse transcriptase to produce DNA from its own RNA genome. The DNA is then incorporated into the genome of the host cell. This DNA can be transcribed to RNA and translated to viral proteins. Perhaps the best known example is human immunodeficiency virus 1 (HIV-1). Most retroviruses infect somatic cells, but occasionally infection of germ line cells occurs, resulting in creation of an endogenous retrovirus (ERV). The genome of mammals is littered with ERVs. Most have been inactivated in the course of evolution. A few, however, are not only expressed but show evidence of purifying selection.

The envelope (env) genes of retroviruses function to promote fusion of the viral membrane with the plasma membrane of a host cell. Syncytins are derived from env genes and are expressed in the placenta, where they promote fusion of cytotrophoblasts with the syncytiotrophoblast. Thus far six syncytin genes have been discovered including two in the mouse and two in higher primates. These genes are not orthologous so each represents an independent capture from a retrovirus. Yet another example of convergent evolution!

There is more. The envelope protein of retroviruses is immunosuppressive and endogenous env genes may contribute to immune tolerance by the mother of the fetal semi-allograft.


  1. My mind was blown in my virology class in college when my professor mentioned that a expression of endogenous retroviral genes was responsible for the development of the placenta. You mention here that six syncytin genes have been discovered (mice and primates), and that they are not orthologous (very cool!) Question: must all mammals have syncytin genes in order for live birth to take place? If so, is it likely that all these genes are endogenous retroviruses?

  2. Syncytins are by definition endogenous retroviral envelope genes. Since I wrote this post, several more have been described. The quickest way to find these papers is by a literature search for Dupressoir and Syncytin. There are many mammals for which evidence of syncytin genes is lacking. However, since establishment of a placenta often involves invasion by syncytial trophoblast, and syncytium formation is promoted by syncytins, some believe that capture of a retroviral envelope (syncytin) gene occurred early in the evolution of placentation in mammals. I find this an interesting hypothesis, but am not convinced. Thank you for your interest in my blog.