Viruses can't survive on their own, and need a host cell to generate more viral particles and spread. So viruses can often manipulate the functions of cells they infect. Researchers have now shown that herpes simplex virus-1 (HSV-1) can rearrange the structure of DNA in human cells that it has infected. In doing so, the virus is better able to get to the host cell genes that it needs to produce more HSV-1 particles. The findings have been reported in Nature Communications.
“HSV-1 is an opportunistic interior designer, reshaping the human genome with great precision and choosing which bits it comes into contact with. It’s a novel mechanism of manipulation we didn’t know the virus had to exploit host resources,” said first study author Dr. Esther González Almela of the Centre for Genomic Regulation (CRG).
The structure of DNA is very important, and cells use various methods to control that structure and rearrange it so that important genes are physically accessible.
Previous studies have shown that herpes viruses can reshape and compact the chromosomes of host cells, and this study has revealed that this is a direct cause of HSV-1, and it happens just hours after infection.
This study has also determined that if the activity of a host cell enzyme called topoisomerase I was stopped, HSV-1 was no longer able to rearrange host genomes. When the enzyme was blocked, the virus was unable to make even one new viral particle, noted corresponding study author ICREA Research Professor Pia Cosma, also of the CRG. As such, the study suggested that these findings could open up new treatment avenues for HSV-1 infection.
In this work, the investigators used super-resolution microscopy to visualize HSV-1 infections in human cells. The virus took control of the human RNA polymerase II enzyme to make its own proteins within an hour of infection. By the third hour, it had harnessed topoisomerase I and cohesin, and most copies of these molecules were no longer working with human genes.
This led to a virtual halt of the transcription of human genes, and the structure of DNA compacted, losing 30% of its volume. This observation came as a surprise.
“We always thought dense chromatin shut genes down but here we see the opposite: stop enough transcription first and the DNA compacts afterwards. The relationship between activity and structure might be a two-way street,” suggested study co-author Dr. Álvaro Castells García.
It's estimated that as many as two of every three individuals have HSV-1, which is typically asymptomatic. Sometimes, it can cause cold sores and in rare cases, it may cause blindness or serious complications in newborns or immunocompromised people.
This work may help lead to effective treatments for HSV-1.
Sources: Center for Genome Regulation, Nature Communications
