Discovery of TMEFF1, a viral restriction factor in the human brain

I ended my previous story with the take home message that the drug discovery field hasn't explored the within-individual biological diversity as much as it has explored the between-individual genetic diversity. And this week, we have another remarkable story that further emphasizes my point.

After completing MD in 2014, I moved from India to Denmark to do a PhD in psychiatric genetics. My interest in psychiatric genetics came from working on a related topic for my MD thesis. That was my entry into the world of human genetics. At that time, I knew little about the field. During my PhD, I learned about the genetics of ADHD, autism, schizophrenia, and other psychiatric diseases. Later, when I began reading broadly, I felt a longing towards certain areas of human genetics like cardiovascular system, endocrinology and metabolism. As I read more, the list grew longer. The latest addition to the list is infectious diseases, particularly the ones that affect children.

Ever since I discovered Jean-Laurent Casanova, an amazing physician scientist at The Rockefeller University, I've been on and off reading about monogenic infectious diseases. Casanova has made tremendous contributions in this area. The first time I learned about him was in early 2022, when I came across two parallel publications in The Journal of Experimental Medicine on the discovery of null mutations in interferon genes that explained the high vaccination-associated deaths in Polynesian Islands and circumpolar regions. I've written about this story previously.

Human immune system has been evolving for over hundreds of thousands of years through continuous arms race against viruses, bacteria, fungi and parasites. For a pathogen, for example, a virus, to infect humans, it has to bypass multiple layers of security measures. It needs to first enter the body, then the cells, then the nucleus if it requires access to host's transcriptional machinery. There are sophisticated sensors in both inside and outside cells that monitor for