Scientists have identified a known cellular protein as a relevant factor for the entry of poxviruses into cells. Pathogens such as the one that causes the eradicated smallpox disease or the Monkeypox virus, which causes monkeypox, belong to this family of viruses. The finding could offer new targets for the development of antivirals.
The work has been carried out by a team that includes scientists from the National Institute for Agricultural and Food Research and Technology (INIA), under the Higher Council for Scientific Research (CSIC) in Spain.
The research has focused on the study of the effect of the inactivation of cellular genes on infection by the vaccinia virus (Vaccinia), known for its role as a vaccine in the eradication of smallpox disease and the prototype virus of smallpox. poxvirus family. To this end, a complete catalog of the human genome has been screened using CRISPR/Cas9 technology.
“Among the cellular genes involved in the infection, we detected one that seemed particularly interesting: the one that encodes beta2-microglobulin,” highlights María M. Lorenzo, INIA researcher and co-author of the study. This protein is part of the molecule recognized by the cells of the immune system (T lymphocytes), but it has multiple additional functions. The work carried out now by the scientists delineates the role of beta2-microglobulin in the virus entry process after the viral particle binds to the cell surface. In the study experiments, while virus binding to cells was not affected, virus internalization and early gene expression were significantly decreased.
“The discovery of its role in infection opens up multiple scenarios both in relation to the virus entry mechanism into the cell and in the face of potential vulnerabilities in this mechanism, which could provide new targets for antivirals,” adds Alejandro Matía, co-author of the study. study.
Microscopic image of poxvirus particles inside the cell. (Photo: INIA / CSIC)
Despite the fact that several cellular proteins are involved in the entry of poxviruses, no single mutation of these genes appears to be sufficient to efficiently prevent infection. “The ability of these viruses to use alternative routes to initiate the infection and take control of the cell is striking,” reflects Rafael Blasco, INIA scientist and co-author of the study. Vaccinia virus (Vaccinia), like other related viruses, is capable of infecting a wide variety of cell types and a multitude of mammals. It is possible that the fact of using different routes of entry plays an important role in allowing a wide range of hosts for the virus and facilitating transmission between different species. Deepening the knowledge of the infection using new technologies allows us to understand the keys to infection by poxviruses, a growing threat to the human population.
The study is titled “Identification of β2 microglobulin, the product of B2M gene, as a Host Factor for Vaccinia Virus Infection by Genome-Wide CRISPR genetic screens”. And it has been published in the academic journal PLoS Pathogens. (Source: INIA / CSIC)