Human adenoviruses (HADV) can take control of cellular waste disposal and reprogram it to their advantage. As researchers at the Helmholtz Zentrum München report in the ‘Journal of Virology’, such an intervention can lead to numerous long-term consequences, including both programmed cell death and uncontrolled division.
Adenoviruses have been researched for more than 60 years, and numerous important findings from cell biology and tumor development can be traced back to corresponding work. “However, the pathogenicity mechanisms of these viruses are still not understood and urgently need to be explored, as there are no specific pharmacological intervention strategies against HADV infections to date,” explains PD Dr. med. Sabrina Schreiner, head of the working group “Antiviral defense of DNA viruses” at the Institute of Virology of the Helmholtz Zentrum München and the Technische Universität München.
In the current work, her team was able to work with scientists around Dr. Ing. Kamyar Hadian from the Institute of Molecular Toxicology and Pharmacology at Helmholtz Zentrum München is now gaining new insights. “We show that the cellular RNF4 protein plays a central role in the infection,” explains study leader Schreiner. “This is a so-called ubiquitin ligase – a protein that marks other molecules for disposal.”
Removal of the virus defense
RNF4 also occurs naturally in the host cell and is only hijacked by the virus in an infection, as the current work shows. “In addition, the virus protein E1B-55K binds to RNF4 and causes it to break down virus defense proteins,” says the first author and doctoral student Sarah Müncheberg the results. Specifically, the researchers demonstrated this with the example of the antiviral protein Daxx (death-domain associated protein). According to the authors, such an intervention in the cellular metabolism can bring about numerous long-term consequences such as the destruction of the cell by programmed cell death, but also the elimination of DNA repair processes, thus contributing to the virus-mediated formation of cancer cells.
“In recent years, HAdV has become more in the focus of virological research,” Schreiner describes the relevance of the results: “In China, the US and Europe, new highly pathogenic adenovirus types have been detected. Unlike before, they not only affect immunocompromised individuals, but for the first time lead to the onset of life-threatening pneumonia even in healthy individuals. “Accordingly, she and her team hope that their findings could lead to new treatment approaches. The project was supported by the Else Kröner-Fresenius Foundation.
Source : Helmholtz Zentrum München