Some of you have been interested in the recent uptick in monkeypox virus infections, as the CDC has just raised the alert after we reached over 1000 infections. If you have completed the Genes Environment and Behavior course you are in for a treat as the most agreed upon theory for the increased transmissibility is an interesting narrative in evolutionary dynamics between host and pathogen and involves human restriction enzymes, viral genome mutations, and knowledge of the central dogma and the resulting nonsense or missense mutations that result.
What appears to be happening is that the monkeypox virus prior to 2017 was adequately managed by the human immune system through a restriction enzyme system that differs from that of the bacterial world. In humans there are gene duplications that have given rise to a family of proteins (APOBECs ) that have the enzymatic function of chemically altering cystines into adenines ( through deamination). The recognition sequence in the viral genome for one of these enzymes happens to be a GG sequence that on the coding strand results in changes most often from tryptophan to STOP. Thus creating viral proteins that are defunct… blocking further viral infection. (See this paper from 2015 to learn more about the proteins)
In 2017, it seems that an outbreak in Nigeria, may have created an environment for selective pressure for those viruses in humans infected with monkeypox, that sustained the hit but managed to slip by with new missense mutations in other parts of their genome resulting in increased transmissibility and potentially mutations that allow it to target the APOBEC human protein with degradation tags, trafficking ABOBEC3 to the proteosome for degradation. Meaning that all the viruses in circulation in humans now share a set of relatively new mutations that all appeared post 2017 ( about 40 in total). ( see this post by Andrew Joseph June 2, 2022, STAT News and a good video on this page as well). The 40 mutations are far too many for the four-year span to be the result of genetic drift (random mutations accumulated over time do to copying errors).
If you are like me, and happen to be either older, or born outside the US you may have been vaccinated for smallpox (this vaccine is a live vaccine of a related virus cowpox) and this vaccination tends to be 85% effective in preventing monkeypox infection. Some in NYC remember the small pox outbreak that resulted in a mass vaccination in 1947 on the streets of the city- so many New Yorkers could be immune (see this historical medical editorial from 2004 about the massive vaccination program and the lack of supply).
Dr. Israel Weinstein, the New York City health commissioner, vaccinating a member of his staff, Doris Wendroff, in April 1947.Credit…Arthur Brower/The New York Times
Stay tuned for more on the evolution of this interesting virus and note that on the heels of multiple pandemics (racism, COVID, poverty) adding one more to the mix is an example of the kind of environment that results in syndemics and zoonoses, and yet another reason there will be much need for those interested in careers in One Health (see this commentary by Singer on a call to action by Rock et al. on Animal-Human Connections,” ‘One Health,’ and the Syndemic Approach to Prevention).