Martedi 11 Febbraio 2025, ore 13
Edificio Asclepio U8-Aula 1
Host: Prof.ssa Manuela Sironi
► Diretta webex
Evolutionary changes in the host-virus interactome can alter the course of infection, but which and how often interactions rapidly evolve and how this is realized at the interface level between the interacting host and viral proteins, remain largely unexplored. Here, we focus on viral mimicry of short host-like motifs that allow efficient binding to host domains by mimicking motifs found in host proteins. We observe that motifs from unrelated viruses preferentially target conserved, widely expressed and highly connected host proteins, enriched with regulatory and essential functions. Host proteins targeted by viral motifs cannot evolve to escape these interactions since mutations in these interfaces will jeopardize host cellular functions and within-host interactions. These host domains therefore represent an Achilles heel in the host interactome that is utilized by viruses.
Thus, in contrast to the prevailing view of rapid evolution at interface regions between host and viral proteins, viruses evolved to exploit constrained host proteins, allowing an efficient interaction that is beneficial for the virus and deleterious for the host. These results have important implications for our understanding of zoonotic events where novel host-virus protein interactions may evolve and for designing new antiviral drugs targeting interface regions between host and viral proteins.
Tzachi Hagai
Shmunis School of Biomedicine and Cancer Research, George S Wise Faculty of Life Sciences, Tel Aviv University, Israel.
I did my BSc at the Hebrew University in Biology & Chemistry, as part of the university's excellence program in sciences.
I did both my MSc and PhD at the Weizmann Institute, working on computational biophysics and bioinformatics of proteins.
I did my first postdoc with Raul Andino, in UCSF, California, on evolution of host-virus interactions in disordered protein regions.
I did my second postdoc with Sarah Teichmann, at the EBI & Sanger Institutes in Cambridge, on evolution of innate immune response using comparative genomics.
I moved to Tel Aviv University and opened my lab there in October 2019.