Scientists at the University of Zurich have discovered the so-called Mib1 protein, which adenoviruses can use to infect human cells. This type of protein signals the virus to remove the DNA and release it into the cell nucleus. For this reason, blocking this protein could help people with weakened immune systems fight dangerous viruses.
Viruses have been a part of animals and humans for eons. When they invade a cell, their genome can reach the cell nucleus. These therefore become part of the infected organism. Viruses transfer their genes between different organisms as well as between tissues that contain well-differentiated cells within a living being. However, how they uncover their well-packaged genes and release them for infection is largely unknown.
The research group led by Urs Greber, Professor at the Institute of Molecular Life Sciences at the University of Zurich (UZH), has now identified for the first time a protein in human cells that is crucial for the successful uncoating of viral DNA: the ubiquitin ligase Mind Bomb 1 (Mib1). .
“The protein allows adenoviruses to remove their DNA and unload it into the cell nucleus – which is necessary for a successful infection,” says Greber.
If the Mib1 protein is not produced or does not function properly, the viruses can enter the cell and reach the nuclear membrane. However, they remain attached to the porous structures of the nuclear envelope. “This finding opens up a new opportunity to develop antiviral therapies that block Mib1 in well-differentiated cells,” says Greber. There are currently no effective medications to combat these common viruses.
Entrance door for viruses
The researchers found the protein by switching off most of the genes in human lung epithelial cells one at a time using RNA interference. They tested whether adenoviruses could infect the cells. “When we inhibited the gene or turned it off using CRISPR-Cas technology, the rate of viral infection dropped dramatically. “Practically all adenoviruses stuck to the pore structures outside the cell nucleus,” says Greber. As soon as these cells produced small amounts of Mib1 protein again after genetic interventions, it reached the viruses at the nuclear pores, whereby the viruses released their genes and infected the cells.
Adenoviruses are widespread in humans and many animals. In humans, they can cause infections of the respiratory and gastrointestinal tracts, as well as the kidneys, liver, eyes and blood cells. Viruses are not life-threatening for healthy people. They simply settle into immune cells, where they remain for months without damaging the cells or tissue. For a person with aweakened immune systemHowever, for example in recipients of stem cell or organ transplants, adenoviruses can easily spread to other cells and become life-threatening.
