How are viruses similar to parasites?

Parasites in the genome

About 30 families of HERV have now been discovered. They are an integral part of the genome and are inherited according to Mendel's rules. Not only have they been preserved for millions of years, they have also "multiplied" in the genome during this time. A mechanism called retrotransposition creates copies of the proviruses that can be distributed across the genome while the proviruses themselves remain in their original position.


Under viral control


Once inserted, there is no way of eliminating the viral DNA. Only by recombination can at least parts of the viral sequences be removed. However, this usually leaves an LTR sequence behind. "This is why there are many more individual LTRs in the genome than proviruses," says Leib-Mösch. They make up about 8.5 percent of the human genome, while complete proviruses only make up 0.5 percent.


Most human endogenous retroviruses are inactive. Since they do not code for proteins that are necessary for the cell, they are prone to mutations. Small errors accumulate and the proviruses become inoperable. In addition, the host cell still has the option to shut down the viral sequences through epigenetic changes, for example through methylation of the DNA sequence, says Leib-Mösch. Nevertheless, some of the viral sequences are read, i.e. transcribed. “In studies, such transcripts were found in all cell types,” says Leib-Mösch. Some transcripts have no function, some code for useful proteins and some for potentially pathogenic proteins. "It is believed that such proteins could play a role in the development of cancer and in the development of autoimmune or neurological diseases," explains the researcher. "Others have a real cellular function."


An example of this is the protein syncitin, which is required for building up the placenta. It is the envelope protein ENV of the human endogenous retrovirus HERV-W that is produced in fetal cells. There it is needed for the formation of a layer of cells in the placenta, which is created by cell fusion. A similar function of retroviruses for the formation of the mother cake was found in sheep and mice. However, these animals use different endogenous retroviruses than humans. In these cases, the hosts not only tolerate the viral parasites in the genome, but have actually taken advantage of them. "In the course of evolution, a small part of the sequences assumed a function in this way," says the biochemist.


This also applies to the LTRs. "Half a million of these sequences are scattered throughout our genome," reports the researcher. “One such sequence is found on average every 7 kilobases.” The LTRs contain the controls for expressing the virus genes. These are start signals to initiate or intensify transcription, as well as stop signals that end the reading of the genes. "If LTRs are integrated in the vicinity of human genes, they can influence their expression," says Leib-Mösch. According to recent research, 5.9 percent of our genes would be controlled in this way. An example of this are the genes for the digestive enzyme amylase. Most mammals only produce this enzyme in the pancreas. However, humans can also produce it in the salivary gland, which is a selection advantage, since the starch in the food can be better broken down. He owes this to a retrovirus, which implanted itself in the vicinity of three amylase genes in the genome and converted the pancreas-specific promoter into a pancreas-specific promoter.


Further examples of genes controlled by viral sequences are the leptin and leptin receptor genes, the products of which are responsible for the control of body fat content. They are both regulated by LTR sequences. But HERV sequences are not only involved in the start of transcription, but in some cases can also stop the reading of genes. Thus, the host has repurposed the viral switches and uses them as switches for its own metabolism.


The viruses have long since lost their harmful effects. But do you always keep calm? Could the retroviruses in the genome regain their infectivity and produce virus particles again? "You can't rule that out," says Leib-Mösch. In the laboratory, various human endogenous retroviruses could be reactivated by a few mutations, which then form virus particles that can infect human cells. Theoretically, this would also be possible in a person. "It may be that this happens in individual cases," says the researcher. It is unclear what the consequences of this will be for those affected. “It cannot be ruled out that these viruses then lead to diseases, whereby they probably do not cause an acute clinical picture, but rather one that sets in much later, such as leukemia.” However, the person affected would in all probability not be able to infect other people and also not trigger epidemics. "The virus is far too well adapted to humans for that," says Leib-Mösch. Humans have come to terms with the parasites in their genetic make-up./