A group of researchers from the University of Oviedo managed to identify new genes involved in the infection of human respiratory and intestinal cells by the SARS-CoV-2 virus that causes covid-19. The results of the work, directed by Prof. Carlos Lopes Otin were published in The EMBO Journal.
Alejandro Pineiro s Gabriel Bretonsresearchers from the Department of Biochemistry and Molecular Biology of the Asturian University and main authors, carried out in this study a complex genetic screening of the entire human genome using genome editing technology CRISPRCas9 until the genes needed for coronavirus infection are identified.
To do this, first of all, they built an artificial version of the SARS-CoV-2 virus through genetic engineering, with no ability to replicate and therefore unable to spread in the environment. They then specifically and individually excluded each of the more than 20,000 human protein-coding genes in human lung cells and interrogated, gene by gene, the cell’s susceptibility to infection with the artificial pseudovirus.
This study led to the identification, among others, of the human genes PLAC8 and SPNS1, encoding proteins involved in biological processes such as endocytosis and autophagy, which may contribute to viral infections.
To corroborate these findings, the authors contacted the then director of the Center for Research in Animal Health (CISA-INIA), Marisa Arias, to carry out experiments with naturally-occurring and fully infectious SARS-CoV-2 viruses. This center is an international reference in the study of infectious diseases and has high biological safety facilities essential for this type of work.
Original first wave virus strain
There the researchers, with the help of the Emerging and Transboundary Diseases group, confirmed their earlier findings using a strain of the original virus (CISA/H-Ap20-1) isolated by the group itself during the first wave of the pandemic.
Piñeiro, first author of the article, highlights that “this is not the first study of this type carried out in the world, but our experimental design based on the use of human lung cells and complex gene editing techniques allowed us to identify genes essential for the infection process that went unnoticed in other studies.”
Furthermore, “unlike others, this work is focused on finding human genes necessary for the initial stages of infection by the virus, before its replication takes place inside the cell”, highlights the researcher.
Our work has focused on finding human genes needed for the early stages of virus infection, before its replication takes place inside the cell.
For his part, Bretones emphasizes that “these hallazgos allow us to better understand the mechanism of internalization of the virus and, therefore, the identification of new therapeutic dianas for the treatment of covid-19 and other diseases caused by coronavirus that can appear in the future. This will allow for the development of targeted therapies to improve treatment and help vaccines stem the spread of the disease.”
Finally, López-Otín highlights that “our laboratory is not dedicated to virology, but in recent years we have developed very advanced experimental methods for the genomic and functional analysis of cancer and aging, which we can now apply to the study of the SARS-CoV coronavirus -two”.
Otín adds that he is “very proud of all the members of my group who, out of sheer social commitmentThey left their private projects in parentheses to dedicate their effort and talent to the study of a virus that showed us with absolute clarity the great truth of human vulnerability”.
The study was funded by the Carlos III Health Institute (COV20/00652), Ministry of Health, Ministry of Science and Innovation and Ministry of Science, Innovation and University of the Principality of Asturias.
Reference:
Alejandro P. Ugalde, Gabriel Bretones, Carlos López-Otín and others. “Autophagy-bound plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells. The EMBO Magazine (September 2022)