Updated: April 29, 2021 11:30:01 am
Coronavirus researchers have discovered how SARS viruses enhance the production of viral proteins in infected cells, so that many new copies of the virus can be generated. Notably, coronaviruses other than SARS-CoV (which causes SARS) and SARS-CoV-2 (which causes Covid-19) do not use this mechanism, the researchers said. This may therefore provide a possible explanation for the much higher pathogenicity of the SARS viruses, they report in the EMBO Journal.
Coronaviruses that cause harmless colds in humans were discovered more than 50 years ago. When it emerged in 2002-03, the SARS coronavirus was the first coronavirus found to cause severe pneumonia in infected people. From comparisons of the RNA genomes of innocuous coronaviruses with those of the SARS coronavirus, researchers identified a region that only occurred in the latter, and was called the “SARS-unique domain” (SUD). Such genomic regions and their protein products might be linked to the extraordinary pathogenicity of SARS coronavirus and its cousin, SARS-CoV-2, they said.
The research groups involved in the new study showed that the SUD proteins of these two viruses interact with a human protein called Paip-1, which is involved in the first steps of protein synthesis. Together with Paip-1 and other proteins in human cells, SUD apparently binds to the ribosomes, the molecular machines that are responsible for protein synthesis in cells. This would lead to an enhancement of the production of all proteins, both those of the host cell and those of the virus. However, in cells infected with SARS-CoV or SARS-CoV-2, the messenger RNA molecules that code for host proteins are selectively destroyed by a viral protein named Nsp1. As a result of this complicated process, the infected cell predominantly produces viral proteins, so that many new copies of the virus can be created.
A research group led by Albrecht von Brunn of Ludwig Maximilian University of Munich discovered the interaction between the proteins SUD and Paip-1 several years ago. “Being an experienced coronavirologist, I knew that one has to inspect the special regions of the SARS genome when trying to understand this virus,” he said in a statement released by Ludwig Maximilian University.
A research group led by Professor Rolf Hilgenfeld of the University of Lübeck, meanwhile, had already elucidated the three-dimensional structure of the SUD protein some years previously. The two research groups teamed up. Dr Jian Lei in Hilgenfeld’s group, a group leader at Sichuan University in Chengdu (China), meanwhile, crystallised the complex formed by SUD and Paip-1 and determining its three-dimensional structure by X-ray crystallography. And co-first author Dr Yue “Lizzy” Ma-Lauer of von Brunn’s group characterised the complex of the two proteins and its function using a variety of cell-biological and biophysical methods, Ludwig Maximilian University said in the statement
“Interaction studies of this kind between coronavirus proteins and proteins of the infected human cell will help us understand how the viruses change key functions of the cell to their own benefit,” the university quoted Hilgenfeld as saying.
Source: Ludwig Maximilian University of Munich
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