Beer, bread and viral genome engineering

We use yeast to make beer and bread, but did you know that we also use yeast for scientific discovery? Yeast play such an important role in science because they are easy to grow and many of their genes are similar to human genes. Most importantly, scientists have developed very efficient methods to modify yeast genomes. This process of genetic manipulation, called recombination, occurs when genetic information is exchanged between strands of DNA; It’s like when people from different cities meet each other and exchange cultural knowledge.

Herpesviruses are major human pathogens that cause lifelong persistent infections, with clinical manifestations that range from mild cold sores to cancer. Perhaps surprisingly, even though there are eight human herpesviruses, we only have a vaccine against one of them, varicella zoster virus, which prevents chickenpox in children in young adults and shingles in older adults. Thus, we desperately need vaccines to combat the other seven human herpesviruses. Taking advantage of the inherent advantages of yeast genetics to manipulate herpesvirus genomes could accelerate vaccine development for these remaining herpesviruses.

One issue that stands in the way of using yeast to study herpesviruses is the fact that these viruses have large (relatively speaking) genomes. In other words, it’s difficult to get herpesvirus genomes into yeast! To get around the issue, a group of scientists decided to break the viral genes of herpes simplex virus type 1 (HSV1) into overlapping pieces. These pieces were then inserted into yeast and the yeast was left to assemble the viral genome using its natural aptitude for DNA recombination. Next, the scientists harvested the newly assembled herpesvirus genome from yeast and put it into mammalian cells that they were growing in the lab. Once inside mammalian cells, the virus genes were turned on and the new herpesviruses were made that resembled natural HSV1. This proved that a virus genome assembled from pieces in yeast could be recovered and used to make new intact viruses in the lab.

Overall, this study showed that yeast could be part of a viable strategy to cheaply and efficiently manipulate herpesvirus genomes. This advance could accelerate the production of precisely engineered weakened virus strains that would be useful for new herpesvirus vaccines. Yeast are already used to make the very effective human papilloma virus (HPV) vaccine that is diminishing rates of cervical cancer and other HPV-linked cancers around the world. This research indicates that the humble baker’s yeast will likely continue to be very a very important part of fundamental and applied vaccine research in the years to come.

Summary written by: Orlando Sosa Díaz

To read the full article, please click the following link:

Genome-wide engineering of an infectious clone of herpes simplex virus type 1 using synthetic genomics assembly methods. 

Lauren M. Oldfield, Peter Grzesik, Alexander A. Voorhies, Nina Alperovicha, Derek MacMathb, Claudia D. Najeraa, Diya Sabrina Chandran, Sanjana Prasad, Vladimir N. Noskova, Michael G. Montague’s, Robert M. Friedman, Prashant J. Desai, and Sanjay Vashee

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