Thursday, 06 May 2021 12:16

In vitro: Hepatitis C virus inhibits transposon mobilization Featured

Using cell cultures, scientists at the Paul-Ehrlich-Institut and the Marburg University Hospital have investigated the interactions between retrotransposons and the hepatitis C virus (HCV). They found that HCV infection can restrict human LINE-1 retrotransposition into cells.

Researchers estimate that about 35 percent of our genome contains sequences that can be traced back to so-called transposons during evolution.  Transposons are DNA segments in the genome that can change their positions in the genome. So-called retrotransposons are derived from retroviruses, which have been successfully combated but their reverse transcriptase enzyme has been incorporated into the genome.

A subclass of retrotransposons, the long interspersed nuclear elements (LINEs), most notably the LINE1 types, still actively transcribe for genes that are thought to cover about 17% of the genome. They can trigger so-called insertion mutations, i.e. insert themselves into important genes, as a result of which they can no longer be read and the actual gene product, such as an important protein, can no longer be produced or cancer can be triggered. Normally, the cell has its own defense mechanisms to shut down the LINE1. However, this can be abolished by viruses.

For their research, the team of scientists led by Prof. Gerald G. Schumann from the Department of Medical Biotechnology at the Paul Ehrlich Institute used a cell line derived from malignant hepatocytes as well as human embryonic kidney cells. They also constructed LINE1 reporter elements.

After infecting the liver cells with HCV, they observed that the genetic information, as well as the formation of proteins of the LINE1 elements, were significantly increased. Via interaction with HCV proteins within the cell, the LINE1 proteins were then transmitted to centers of HCV particle assembly. Concurrently, however, the researchers found that HCV replication disrupted the retrotransposition of LINE1 reporter elements constructed in the experiments.  Accordingly, HCV infection has at least a negative effect on LINE1 mobilization.

Original publication:
Schöbel A, Nguyen-Dinh V, Schumann GG, Herker E (2021): Hepatitis C virus infection. restricts human LINE-1 retrotransposition in hepatoma cells. PLOS Pathog Apr 19 [Epub ahead of print].

Press release:
https://www.pei.de/DE/newsroom/pm/jahr/2021/08-hcv-infektion-beeinflusst-mobile-genetische-elemente-leberkrebszellen.html

Additional:
DocCheck Flexicon Transposon. https://flexikon.doccheck.com/de/Transposon