Until now, scientists had assumed that there are about 80 so-called open reading frames (ORFs) in the genome of herpes simplex virus 1 (HSV-1). These are the locations in the genome where the information in the DNA is read and translated into proteins. It is now clear that there are a lot more - namely 284 ORFs. These are translated from hundreds of novel viral transcripts, which have now also been identified and reported in the journal Nature Communications.

The research team used a broad spectrum of the latest systems biology methods for the study. The data are not only important for a better understanding of the virus itself. They also have concrete implications, for example for the development of HSV-1-based oncolytic viruses. These are viruses that are used in immunological therapies of certain tumor diseases, such as malignant melanoma.

The authors identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic.

Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. The authors show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins.

They extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution.

Herpes simplex viruses of type 1 (HSV-1) are known to many people as the cause of unpleasant itching cold sores. An infection with this virus type can also have serious consequences. For example, HSV-1 can cause life-threatening pneumonia in patients in intensive care units. And in healthy people, it can cause encephalitis, which often leads to permanent brain damage.

Once infected with the virus, a person will retain it for the rest of his or her life: herpes viruses permanently nestle in body cells. There they usually remain inconspicuous for a long time. Only under special circumstances, such as a weakened immune system, they become active again.

https://www.uni-wuerzburg.de/aktuelles/pressemitteilungen/single/news/herpesvirus-entschluesselt-1/

https://www.nature.com/articles/s41467-020-15992-5

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fintegrative-functional_2&filter=22